Costs and Effectiveness of Colorectal

Cancer Screening in the Elderly

September 1990

OTA-BP-H-74

NTIS order #PB91-104877
Recommended Citation:

U.S. Congress, Office of Technology Assessment, Costs& Effectiveness of Colorectal Cancer

Screening in the Elderly-Background Paper, OTA-BP-H-74 (Washington, DC: U.S.

Government Printing Office, September 1990).

For sale by the Superintendent of Documents

U.S. Government Printing Office, Washington, DC 20402-9325

(order form can be found in the back of this report)
COSTS AND EFFECTIVENESS OF COLORECTAL CANCER

SCREENING IN THE ELDERLY

Judith L. Wagner, Project Director

Brigitte Duffy, Research Analyst

Sandeep Wadhwa, Research Assistant

Lara Jakubowski, Research Assistant

Health Program

Office of Technology Assessment

U.S. Congress

Washington, DC 20510-8025

September 1990

A Background Paper

in OTA’s Series on

Preventive Health Services Under Medicare

This report was prepared for desk-top publishing by Eileen Murphy and Carolyn Martin.

The views expressed in this Background Paper do not necessarily

represent those of the Technology Assessment Board,

the Technology Assessment Advisory Council,

or their individual members.
has

Interest in health promotion and disease prevention strategies for the elderly

grown in the last 10 years, at least partly as a result of the search for ways to

moderate the rising costs of health care in this growing segment of the population.

Reflecting this interest, the House Committee on Ways and Means requested that

OTA analyze the costs and effectiveness of providing selected preventive health

services to the elderly under the Medicare program. The Senate Labor and

Human Resource Committee had earlier requested that OTA provide information

on the value of preventive services for the American people.

OTA responded with a study of the effectiveness and costs of four specific preventive services for the elderly: glaucoma screening; cholesterol screening; cervical cancer screening; and, in this background paper, colorectal cancer screening.

In this paper OTA summarizes the evidence on the effectiveness and costs of

colorectal cancer screening in the elderly and explores the implications for

Medicare of offering this preventive technology as a Medicare benefit. Nowhere

are the hard choices between potential medical benefits and high costs illustrated

more clearly than with this cancer screening technology.

/J’f @’fLA# ‘ ~ >

JOHN H. GIBBONS

Director

. . .

i i i
CONTENTS

Chapter Page

Executive Summary.....* *** ● * . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ● ...0.00.. ● *.***.*.* ...0..00.0 ● . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ● . . . . . . . . . ● 0..00..0. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Evidence on Effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ 2

Potential Cost-Effectiveness of CRC Screening in the Elderly. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Implications for Medicare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ 5

10 The Rationale for Colorectal Cancer Screening .......................................................................................................... . . . . . . . . . . . . . . . . . . . . . . . ......7

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .............. ................. 7

Technologies for Colorectal Cancer Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Recommendations for Colorectal Cancer Screening in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

The United States. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .......... 10

Other Countries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............. 12

Understanding the Differences in Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

2. The Effectiveness of Colorectal Cancer Screening . . . . . . . . . . ● .....0... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ● . . . . . . . . . . . 13

Issues in Measuring Effectiveness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Evidence on Effectiveness of Fecal Occult Blood Test (FOBT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Evidence on the Effectiveness of Sigmoidoscopy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Effectiveness Issues Specific to the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3. The Cost-Effectiveness of Colorectal Cancer

Screening in the Elderly.. ● ● . . ● ● ● ..•.• ● . . . ● . ● . . ● . . . . . ● . ● . . ● ● ● . . ● . . . . . ● . ● . . . . . ● . . . . ● . . ● . . ● . . . . ● ● . ● . . . . . ● . . ● . . . . . . ● . . . ● ● . . ● ● ● ● ● ● . . . . . . . ● . . . ● . . ● ● ● . . . . . . ● . . . . . . . . ● . ● . . ● ● ● ● .23

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... .......................... 23

Screening, Follow Up, and Surveillance Strategies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Structure and Assumptions of The Cost-Effectiveness Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... ............................ ...... 26

Distribution of Effects Across Time and Individuals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Sensitivity Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ 30

Comparison With Other CRC Cost-Effectiveness Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... .. 33

Implications for Medicare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... 33

Appendix

A. OTA Advisory Panel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. ...................... 35

B. Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... .......... ......... 36

C. Basis for Cost-Effectiveness Analysis of Colorectal Cancer Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Measurement of Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... ... 37

Natural History of CRC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Accuracy of Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 39

Medical Risks of Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Years of Life Gained From Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Measurement of Costs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 46

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... ........................ . 49

iv
CONTENTS-continued

Boxes

Boxes Page

A. Staging Colorectal Cancers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... 7

B. Polyps and Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... ............. 9

Charts

Charts Page

1. Annual Colorectal Cancer Incidence Rates, United States. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2. Annual Cost of Colorectal Cancer (CRC) Screening, Followup, and Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Tables

Table

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

c-1.

c-2.

c-3.

c-4.

c-5.

C-6.

Page

Stage at Detection of Colorectal Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Recommendations for Screening for Colorectal Cancer in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Fecal Occult Blood Test (FOBT) Controlled Clinical Trials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15-16

Age-Specific Polyp Prevalence: Autopsy Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Effects and Costs of CRC Screening in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Summary of Assumptions for Cost-Effectiveness Analysis, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Cost-Effectiveness of Colorectal Cancer in the 1989 U.S. 65-Year-Old

Population Under Assumptions Unfavorable to Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Impact of Surveillance Schedule on the Cost-Effectiveness of CRC

Screening in the 1989 U.S. 65-Year-Old Population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Cost-Effectiveness of CRC Screening Under Differing Assumptions

About the Cost of Treating Early and Late CRC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Sensitivity of Cost-Effectiveness Results to Faster Polyp/Cancer

Progression Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................. 31

Effect of Lower FOBT Sensitivity on Cost-Effectiveness of CRC Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Assumptions Underlying Estimates of the Annual National Costs

of CRC Screening, Followup, and Surveillance in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

FOBT Sensitivity and Specificity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

Distribution of Polyps by Location From Autopsy Studies of U.S.

and Foreign Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 43

Distribution of Polyps from Studies of Symptomatic Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Selected Screening, Followup, and Surveillance Charges for Colorectal Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Average Charges Made to Medicare for Treatment During the Initial,

Continuing, and Terminal Phases of CRC (1984 dollars) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Estimates of the Cost of Treating Early and Late Cancers in 1988 Dollars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

v
Executive Summary

Cancer of the colon or rectum -- commonly

referred to together as colorectal cancer (CRC) -- is 1 Every year, about primarily a disease of the elderly.

110,000 people 65 years of age and older are diagnosed with CRC. Almost three out of every four

new cases of CRC occur in people 65 years of age

and older. In 1989, about 61,500 people died from

the disease. A 65-year-old man without previously

diagnosed CRC has about 6 chances in 100 of

ultimately developing CRC, and about 3 chances out

of 100 of eventually dying from the disease (134). As

a person ages, the risks of CRC increase dramatically. At 50 years of age, the incidence of CRC in

men is 57 per 100,000; by 65 years of age, it has risen

to 244 in 100,000; and by 75 years of age it is 411 in

1Colorectal cancer is also referred to as cancer of the large

bowel, the portion of the alimentary canal that begins at the

cecum, the juncture between the small intestine and the large

intestine, and ends at the anus.

Chart l--Annual Colorectal Cancer

200 }

100

0

100,000. Though women have a lower overall

incidence rate for CRC, it still rises dramatically with

age, from 46 per 100,000 at 50-54 years of age to 156

per 100,000 at 65-69 years of age (chart 1).

Although environmental factors, particularly diet,

appear to play a role in the development of CRC,

little is known today about how to prevent CRC

through dietary or environmental interventions.

Promising new approaches to cancer therapy appear

to offer significantly better prognosis for people with

moderately advanced colon cancer, but these

improvements are likely to have only modest impacts

on overall survival rates for late stage CRCs. Thus,

clinicians and researchers have sought ways to

reduce the burden of illness and death associated

with CRC by detecting more cancers in early and still

curable stages, before they progress to more

advanced stages.

Incidence Rates, United States

SOURCE: U.S. Department of Health and Human Services, National Cancer Institute, Cancer Statistics Review 1973-1986

(Bethesda, MD: May 1989)

-1-
2- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

If early detection of CRC can interrupt or delay

the natural course of the disease, then detection and

removal of the suspected precursors to cancer --

adenomatous polyps (benign growths in the colon or

rectum) -- might actually prevent the onset of cancer

itself and lower its incidence. Thus, the notion of

CRC screening has come to encompass a search not

only for early cancers, but also for the benign

adenomatous polyps out of which most CRCs are

suspected to arise.

The detection of neoplasms (cancers and adenomatous polyps) in the colon or rectum involves either

direct inspection of the colon and rectum or indirect

measurement of biochemical markers for the

presence of cancer or polyps. Today, the most

common screening technologies are the fecal occult

blood test (FOBT), which analyzes samples of stool

for the presence of blood, and flexible fiberoptic sigmoidoscopy (FSIG), a flexible tube with a light and

mirror at the end inserted into the colon through the

anus to examine the dista12 end of the large bowel.

The full impact of screening does not end with

these tests. Over the course of his or her remaining

life, an elderly person would not only undergo

repeated CRC screening tests but also followup diagnostic testing when the screening tests are positive,

polyp removal (polypectomy) when polyps are found

as part of the screening or followup tests, and

periodic surveillance with colonoscopy after

polypectomy to screen for new polyps. In addition,

when cancers are found, patients undergo evaluation

and treatment for the cancer based on the stage at

detection.

Numerous expert groups in the United States and

other industrialized countries have made recommendations “about the frequency with which elderly

people should receive particular colorectal screening

2.Distal” refers to the parts of the large bowel closest to the anus.

“Proximal” is the term for the part-of the large bowel that is

closest to the cecum, the point of juncture between the small

intestine and the large intestine.

tests. Although the American Cancer Society and

the National Cancer Institute both recommend

periodic screening for CRC with an annual FOBT

and FSIG every 3 to 5 years for all Americans

beginning at age 50, the U.S. Preventive Services

Task Force, an expert group sponsored by the U.S.

Department of Health and Human Services, declined

to recommend either for or against periodic

screening with either FOBT or sigmoidoscopy in

average risk individuals.

The differences in recommendations regarding

CRC screening for average-risk older people reflect

two facts. First, the evidence on the effectiveness of

specific CRC technologies is inadequate; and second,

the criteria (either implicit or explicit) for judging the

evidence that does exist differ among the expert

groups. At issue is whether a screening test for CRC

must be shown to reduce CRC incidence or mortality

in order to be considered effective, or whether

demonstrating a shift in the distribution of detected

cancers to earlier stages is sufficient for considering a

screening regimen effective. Those who require

direct evidence that CRC screening will reduce the

incidence of or mortality from CRC have found the

existing evidence inadequate to recommend

embarking on a screening strategy for CRC. The

critics also point out that screening and diagnostic

follow-up have medical risks and costs. Advocates

focus on the heavy burden of illness and death

brought about by CRC and conclude that even

indirect evidence that screening may alter the course

of a substantial proportion of such cases cannot be

ignored.

EVIDENCE ON EFFECTIVENESS

Although a large literature exists on the use of

the FOBT as a strategy for CRC screening, only six

controlled studies of FOBT screening in asymptomatic individuals have been reported, and four of

these are still underway. All but one of the studies

are large randomized clinical trials conducted in

older average-risk individuals, beginning at ages 45 to

60-years-old. The exception is a study of volunteers
Executive Summary -3

over 40 years old attending a cancer prevention clinic

in New York City who were assigned to the experimental or control group according to the month in

which they presented at the clinic.

Despite imperfect compliance, rates of detection

of CRC are consistently higher in the intervention

groups than in the control groups, and a higher proportion of those found are early cancers. Only one

of the trials has reported on mortality differences

between intervention and control groups. A large

trial of biannual FOBT screening of 45- to 70-yearolds in Denmark found a 27 percent lower CRC

mortality rate in the group offered screening after

about 3 years of study, but the number of deaths in

the study so far is very small and the difference is not

statistically significant by conventional standards.

To summarize, the six controlled studies of

FOBT screening suggest that in an ongoing screening

program, FOBT screening improves the stage distribution of cancers detected, which may translate

into decreases in cancer mortality. However, even in

very large trials, no such mortality effect has been

identified to date.

Studies of the impact of sigmoidoscopic screening

on cancer incidence or mortality are even fewer than

for FOBT. Only three studies of outcomes of

screening programs using sigmoidoscopy have been

reported. TWO of these were long-term observational

studies of screened subjects without comparison

groups. The third was a randomized clinical trial of

rigid sigmoidoscopy as part of a program of periodic

preventive health services offered to non-elderly

enrollees in an Hospital Maintenance Organization

(HMO).

These studies have universally shown dramatic

shifts of detected cancers to early stages. Although

two of the three studies reported declines in the

incidence or mortality of cancers, critics have concluded that attribution of such changes to screening

is not possible given the studies’ methods.

Taken as a whole, the evidence on FOBT and sigmoidoscopy suggests a major shift in the stage at

which CRCs are detected but inadequate evidence

that this stage shift actually reduces death rates from

cancer over time. How can these two seemingly contradictory findings be reconciled? One possible

explanation is that there are biases in the detection

of cancers in these studies. The stage shift may

reflect earlier diagnosis, not improved outcomes.

This greater “lead time” between diagnosis and death

would improve the stage distribution of cancers

detected without affecting mortality in randomized

trials. There is also a real possibility that “length

bias” -- the higher rate of detection of the slowest

growing tumors which by definition are less lethal

than faster growing tumors -- may account for the

inconsistency. Those who believe that length bias

can be a powerful influence on outcomes are likely to

discount the evidence on stage shift as inadequate,

whereas those who see the dramatic shifts in stage at

detection as unlikely to be caused simply by lead time

or length bias accept this evidence as sufficient to

justify periodic CRC screening with sigmoidoscopy

or FOBT.

POTENTIAL COST-EFFECTIVENESS

OF CRC SCREENING IN THE ELDERLY

Cost-effectiveness analysis is a process of comparing the net health care costs brought about by a

screening strategy with the health effects achieved as

a result. Estimating the cost-effectiveness of CRC

screening in the elderly is a difficult undertaking

because of the uncertainty about whether CRC

screening is effective at all in preventing CRC or

reducing its lethality. If CRC screening is not

effective in reducing CRC incidence or mortality in

the elderly, then it is clearly not cost-effective. It is

only costly. It may even be both costly and risky,

because the screening and followup procedures associated with CRC screening strategy carry their own

medical risks.

Whether CRC screening can extend the lives of

elderly people through prevention or earlier

detection of CRCs is simply unknown at present.

Indirect evidence does exist, however, about the

natural course of the disease, the accuracy of the

various screening tests in detecting polyps and CRC,

rates of medical complications associated with the

various tests and cancer treatment, and the life
4- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

expectancy of people with CRC at various stages.

Though this evidence is imperfect and has some

important gaps, if used judiciously it is possible to

explore the potential impact of CRC screening on

the health of elderly people. These potential net

health impacts can then be compared with the net

health care costs associated with screening in elderly

people.

To resolve the dilemma posed by uncertainty

about net effects, the Office of Technology

Assessment (OTA) estimated the net health care

cost per additional year of life gained from CRC

screening using data and assumptions that were in

every case unfavorable toward screening. OTA

examined the existing evidence on screening test

accuracy, the natural course of the disease in the

elderly, medical risks, and costs with the objective of

deliberately underestimating the effectiveness and

overestimating the costs associated with screening. If

the resulting conservative estimate of cost-effectiveness of CRC screening compares favorably with

other preventive interventions for the elderly, particularly those that have already been included as

Medicare benefits, then confidence that CRC

screening is at least as cost-effective as these other

services would be high.

Some experts argue that such an analysis is

inappropriate at this time (20). Because there is no

direct evidence of effectiveness for either FOBT or

FSIG, critics argue that an analysis that predicts any

positive health effects is not truly pessimistic; a truly

pessimistic analysis would posit no health effects.

Moreover, evidence on FOBT may become available

within the next two to five years as the five ongoing

or completed clinical trials report their results. A

large National Cancer Instutitue (NCI)-sponsored

trial of FSIG screening in older people is also in

planning and will probably provide information on

that screening procedure within the next 15 years. In

the absence of the direct evidence that can come only

from these trials, critics argue, an assessment of the

medical benefits and potential cost savings associated

with screening would entail too many unproven

assumptions. Given the high costs and potential

medical complications of screening in the elderly, the

most prudent strategy is to wait a few years for the

results of such studies before deciding whether to

take any action, such as providing a Medicare CRC

screening benefit, that would encourage screening in

the elderly.

The proponents of this view reject the value of

the substantial body of indirect evidence that does

exist on the accuracy of the screening tests, the

natural course of the disease in the elderly, and the

effectiveness and cost of treating CRC. It is also not

clear that the existing FOBT trials, even when they

are reported, will settle the question of FOBT

screening effectiveness once and for all. If results

differ across trials, for example, the reasons for such

discrepancies could be debated for years. Most

important, a decision to wait must be recognized as

carrying its own implicit value judgment that the

potential lives saved from CRC screening are not as

important as the potential medical risks and costs of

undertaking screening. OTA’s analysis is intended to

explore just how great the potential gains from

screening might be using what information is

available now.

OTA constructed a model of the cost-effectiveness of periodic CRC screening in a population at

age 65 and continuing until they die or reach the age

of 85. OTA made pessimistic assumptions (i.e.,

biased against finding in favor of screening) about

the accuracy of the screening tests, the speed of

progression of polyps to cancer and cancers from

early to late stages, the proportion of cancers that

arise out of polyps, the stages at which cancers would

be found in an unscreened elderly population, and

the impact of early detection of CRC on life expectancy.

OTA found that a CRC screening regimen consisting of an annual FOBT beginning at age 65 would

prevent approximately 23,000 cases of CRC in the 2.1

million people who were 65 years of age in 1989 and

would provide almost 45,000 added years of life to

that population. 3 These benefits would come at a net

discounted cost of roughly $1.5 billion over the

remaining lives of the people in the cohort. This net

lifetime expenditure amounts to about $737-$1,263

3Both added yearn of life and costs are discounted at 5 percent

per year.
Executive Summary -5

for every person who complies with screening, diagnostic protocols and surveillance guidelines. The net

cost per added year of life is about $35,000.

Screening strategies that combine annual FOBT with

sigmoidoscopy prevent more cancers and add more

years of life but are also more expensive; consequently, the net discounted health care cost per

added year of life ranges from approximately $42,000

to $47,000 depending on the frequeney with which

sigmoidoscopy is included in the screening program.

Studies of other preventive services legislated as

covered services under Medicare in the past

(pneumococcal pneumonia vaccine, cervical cancer

screening, and breast cancer screening) have

reported lower costs for each additional year of life

gained from screening. However, when both costs

and years of life gained were discounted to their

present value at an annual rate of 5 percent, as they

were in this study, breast cancer screening in elderly

women was estimated to cost about $34,000 per year

of life gained. This is approximately equal to the cost

per year of life gained from annual FOBT screening

in the elderly under the pessimistic set of assumptions.

OTA attempted to submit CRC screening to a

stringent test of cost-effectiveness by making

assumptions that were uniformly unfavorable to

screening. For most of the assumptions, we are reasonably confident that the true value is more

favorable to screening than the value assumed in the

analysis. By combining so many unfavorable

assumptions together, the analysis represents a reasonable upper bound on the potential costs per year

of life gained from each screening regimen. Data

were sparse to support several assumptions, however.

A test of how sensitive the results of the study are to

changes in the assumed costs of treating cancer

determined that even if such costs are as low as

$5,000 per case for both early and late cancer, the

4Mammography was briefly legislated as a covered benefit under

Medicare, but the provision was repealed when the Medicare

Catastrophic Health Act of 1988 was repealed late in 1989.

discounted net cost per year of life gained from

annual FOBT screening is still under $40,000. The

results of the analysis were more sensitive to a

change in assumptions about the speed with which

colorectal polyps become cancers. If a very rapid

rate of progression is assumed, the cost per additional year of life gained by an annual FOBT could

be as high as $50,000. The ability of the FOBT to

detect early cancers (FOBT sensitivity rate) also has

a major influence on the outcome of the analysis. If

FOBT is a very poor detector of early cancer, the

cost per year of life gained from annual FOBT

testing in the elderly could be as high as $47,000.

To summarize, the net health care costs of any

CRC screening strategy are high. The present value

of the lifetime health care costs of an annual FOBT

screen for the 2.1 million people who were 65 years

old in 1989 may be as high as $1.5 billion, but these

high costs have the potential for adding 45,000 years

to these people’s lives, and the net costs per added

year of life are within a range that has been judged

reasonable for one other screening examination

(mammography) that had been legislated as a

Medicare benefit.

The lifetime health care costs of screening

strategies that include FSIG as well as FOBT are

even higher than those for FOBT alone ($2.4 billion

to $2.6 billion, depending on the frequency of FSIG

screening), and the added health benefits associated

with FSIG over and above FOBT may be quite low.

Thus, the additional cost per added year of life

gained for FSIG screening over and above FOBT

screening may be much higher than those of other

preventive services that have been legislated as

Medicare benefits.

IMPLICATIONS FOR MEDICARE

If CRC screening were a covered Medicare

benefit, Medicare’s share of the net cost of screening

would be high. Even today, Medicare covers a large

but unknown proportion of the total net costs of such

a screening strategy, because all diagnostic, followup,

and surveillance procedures are covered Medicare

services. The costs of the screening tests themselves,
6- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

particularly the FOBT, are very low compared to the

costs of followup, treatment, and surveillance.

Medicare’s average allowed charge for the FOBT

when it is ordered for diagnostic reasons is under $4

and for FSIG is about $100.

The national cost estimates above are based on

the assumption that all elderly Medicare beneficiaries will follow the screening regimen outlined in

the model. In reality, the use of CRC screening

examinations in the elderly is quite low, and it is

unknown how much it will increase by making FOBT

alone or in combination with FSIG a covered

Medicare benefit. In 1987, for example, only 34

percent of people 60 years of age or over reported

ever having undergone a screening FOBT test and 7.4

percent reported ever being screened with proctoscopy (rigid sigmoidoscopy) Thus, the net additional health care cost of a Medicare CRC screening

benefit may be much lower than the estimates given

here. On the other hand, if screening is differentially

used by those at low risk of CRC, then the medical

benefits projected in the cost-effectiveness analysis

would be reduced, and the cost per year of life added

would be higher.

The total costs of CRC screening to Medicare

and beneficiaries also depend on the amount that

Medicare pays for screening, followup and surveillance examinations. In the estimates of screening

costs, OTA used Medicare’s average allowed charges

in 1988 for procedures conducted in physicians’

offices. To the extent that FOBT and endoscopy

procedures are billed at rates above these amounts

and physicians do not accept assignment of the

Medicare allowed amount as reasonable, these

allowed charges underestimate total health care

costs. In addition, when followup and surveillance

colonoscopies are performed in hospital outpatient

departments, Medicare also pays the hospital for the

technical costs of the procedure. If Medicare cannot

limit the payment rates for surveillance colonoscopies to the average amounts allowed in physicians’

offices, the actual outlays could be higher than the

estimates given in this paper.

Finally, the net costs of the strategy are very

sensitive to the frequency with which CRC screening

results in followup or surveillance colonoscopy. If

physicians recommend and patients who have had

adenomatous polyps removed comply with a frequent

schedule of surveillance with colonoscopy (every two

years instead of every four), the costs of the strategy

could be much higher than estimated in this paper.

The extra costs could amount to almost $1 billion

over the lifetime of the 1989 65-year-old population if

all members of the population fully comply with the

protocol.

This analysis highlights the substantial net costs

that can be associated with a preventive service, even

one that offers a high potential for major health

benefits. CRC screening in the elderly will NOT

reduce total health care costs. Depending on which

tests are employed and how widely they are used,

screening may raise the total lifetime health care cost

for a 65-year-old person who undergoes screening as

a result of a Medicare benefit by as much as $1,300.

That expenditure, which will be borne in large part

by Medicare, offers a good chance, but not a certainty, of providing elderly people with substantial

gains in health.
Chapter 1

The Rationale for Colorectal Cancer Screening

INTRODUCTION

The argument for colorectal cancer (CRC)

screening rests on evidence that patients whose

cancers are detected in earlier stages do much better

than patients with more advanced cancer on

detection. Patients whose cancers are detected in

early stages (Dukes’ Stage A and B--see box A on

cancer stages) have an 85 percent 5-year relative survival rate compared to 38 percent in patients with

late cancer (Dukes’ C and D) (152). The availability

of curative surgery for localized disease is a primary

reason for these differences in survival (23,145).

If people wait for symptoms before seeking care,

the distribution of detected cancers by stage contains

a high proportion of more advanced cancers. Table

1 shows the stage distribution of cancers reported in

various studies. The high death rate from CRC in

this country -- almost one-half of all CRC victims die

within five years of the detection of the disease -- is a

reflection of the preponderance of cancers detected

at later stages.

Although environmental factors, particularly diet,

appear to play a role in the development of CRC

(112,162), little is known today about how to prevent

Box A--Staging Colorectal Cancers

The primary purpose of staging systems is to indicate the severity of the disease state. There are, however,

several other important functions of classification systems. They are used for treatment planning, comparing

results of different studies, and predicting recurrence patterns and survival rates (23). The staging of colorectal

cancer is muddled by the presence of several staging systems that use the same nomenclature to represent different disease states.

The Dukes’ system is one of the oldest and most commonly employed colorectal cancer staging systems.

Cuthbert Dukes, a pathologist at St. Mark’s Hospital, London, England, is responsible for much of what we

know about the spread of colorectal cancer (23). He performed meticulous gross and microscopic studies of

over 2,000 rectal cancer specimens and concluded that a patient’s prognosis was significantly correlated with the

depth of invasion of the tumor and with the presence or absence of lymph node spread (145). The chance of

recovery diminishes as the carcinoma penetrates into the bowel wall.

In 1930, Dukes proposed a three-letter classification system for rectal cancers based on his findings; this

system was revised in 1967 by Turnbull to include a fourth stage (23,145).

o Stage A indicates the least severe disease state: the cancer penetrates into but not through the bowel wall.

o Stage B represents penetration through the bowel wall, but no invasion of the lymph nodes.

o Stage C indicates involvement of the lymph nodes regardless of the extent of bowel wall penetration.

o Stage D, the most advanced stage, indicates the presence of a primary tumor, lymph node invasion, and the

presence of distant metastasis.

Since 1930 many investigators, including Dukes, have proposed modified staging systems. These systems

express finer degrees of penetration and nodal involvement. The existence of several staging systems has made

it difficult to compare the results of clinical studies. In an effort to modernize and simplify staging systems, the

American Joint Committee on Cancer and the International Union Against Cancer recently proposed the TNM

Classification system (23). TNM may replace Dukes’ system, but almost all of the current studies employ

Dukes’ staging.

-7-
8- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

Table 1 -Stage at Detection of Colorectal Cancers

Stage at detection a

study Population ABC D

Allison & Large HMO

Feldman, without

196& screening

program,

1974 25% d 29% d 23% d 11% d

Holmes Missouri 34.6%e

47.4%0 17.996°

et al., 1961b

Tumor

Registry,

1944-79

U.S. DHHS, Tumor 37%e

4 1 %

e 2 2 %e

1989C Registry

(selected

sited

SOURCES:

aJ.E. Allison and F. Feldman, “C@ Benefits of Hemoccult Screming for Colomctal

Careinomx” Dg. CYs. Sci. 30(9):S60-S65, 19S5.

b F.F. HolmM and E. Heame, ‘Cancer Stage-To-Age Relationship: Implications fOr

Cancer Screening in the Elderly,= J. Am. Gariair. Soo. 29(2):55-57, 1SS1.

c U.S. Department of Health and Human SeMcae, Public Health Servlee, National lnstitutae of Health, National Cancer Institute, Cancer !hltiSffCs Rdew 1973-1988

(Betheed~ MD: 1!3SS).

d Re@gd by Dukee’ A, B, C, or D

e RewR~s 1~, regional, or Widmpti.

CRC through dietary or environmental interventions

(136). Although new approaches to cancer therapy

for Stage B and C colon cancers appear to be promising (97,102), they are likely to have only modest

overall effects on survival rates from late CRCs.

Thus, the most promising opportunity at present for

reducing the burden of illness and death associated

with CRC is to detect more cancers in early and still

curable stages, before they progress to more

advanced stages.

If early detection of CRC can interrupt or delay

the natural course of the disease, then detection and

removal of the suspected precursors to cancer --

colorectal adenomatous polyps -- might actually

prevent the onset of cancer itself and lower its

incidence. Thus, the notion of CRC screening has

come to encompass a search not only for early

cancers, but also for the benign growths, referred to

as adenomas or adenomatous polyps, out of which

most CRCs are suspected to arise (44,115). Not all

colorectal polyps are adenomas (a large number are

“hyperplastic”, a type of polyp that is thought not to

progress to cancer (88,118,167). It is believed that

only a small proportion of these adenomas -- as few

as 5 to 10 percent -- will progress to cancer, (35,71,

106), but clinicians and researchers generally agree

that the vast majority of CRCs begin as benign

adenomas (12,108,118)(See box B for a description

of polyps and their relationship to CRC.).l Thus,

detection and removal of adenomas is a second

objective of CRC screening.

TECHNOLOGIES FOR COLORECTAL

CANCER SCREENING

The detection of neoplasms (cancers and

adenomas) in the colon or rectum involves either

direct inspection of the large bowel or indirect

measurement of biochemical markers for the

presence of cancer or polyps. Direct inspection of

part or all of the 145 cm-long (57 inch) large bowel

can be accomplished with a digital rectal examination, with endoscopes of various lengths, or with

the barium enema, an x-ray examination of the colon

and rectum. At present, indirect tests are limited

largely to measurement of the presence and quantity

of hemoglobin in the stool, although other tests, such

as one measuring occult albumin in the stool (110)

and another using a sample of mucin from the

rectum, are currently under development (99).

In the digital rectal examination, the clinician

inspects the interior of the rectum with a finger in

search of a rectal mass. The reach of this examination is limited to 7 to 10 cm (3 or 4 inches), so it is

unable to identify the vast majority of colorectal

neoplasms, which arise beyond the area of

inspection.

Endoscopy refers to the insertion of a tube with a

light and mirror at the end into the gastrointestinal

tract for direct visualization of its interior. Before

the late 1970s, endoscopes were made of rigid

materials and could be inserted through the anus

only about 20 cm (8 inches) to the distal end of the

sigmoid colon. These rigid sigmoidoscopes, or proctoscopes, are still used to screen for colon cancer, but

1Definitive proof that CRC begins with polyps is not available,

however. See Castleman (19) for reasons not to accept the polypcancer sequence.
Chapter 1--The Rationale for Colorectal Cancer Screening -9

Box B--Polyps and Cancer

There are two major types of colorectal polyps: neoplastic and non-neoplastic. Neoplastic polyps are called

adenomatous polyps, or adenomas. They constitute between 50 and 75 percent of all polyps (118,167) and have

a malignant potential.

The proportion of adenomas that progress to cancer appears to be very small. Several authors have

estimated that 5 to 10 percent of adenomas will progress to cancer (35,71). The rationale for this estimate is

based on studies determining the invasive malignancy rate of polyps. Morson estimated that 11 percent of all

adenomas contain cancers. Assuming that at least some carcinomas originate in adenomas, one can conclude

that many polyps do not progress to cancer, since adenomas have a much higher prevalence than carcinomas.

In addition, observations of patients with familial polyposis (an inherited condition in which many polyps arise

beginning in early adulthood) show that over time only a few out of hundreds of polyps progress to cancer

(106).

The type of adenomatous polyp and its size are indicators of its malignancy potential. Villous polyps and

intermediate type polyps have higher malignancy rates than tubular adenomatous polyps (106,113). Many

investigators have determined that the diameter of the adenoma is positively correlated with the incidence of

invasive malignancy. Muto and colleagues estimated that adenomatous polyps less than 1 cm had an incidence

of invasive malignancy of 1 percent; polyps between 1 and 2 cm, an incidence of 10.2 percent; and polyps

greater than 2 cm an incidence of 34.7 percent (109). More recent data from the National Polyp Study indicate

a similar positive correlation between adenoma size and presence of invasive cancer, but the incidence of

invasive cancer in the adenomas studied was much lower than that found by Muto (113).

they now must compete with newer flexible fiberoptic

endoscopes, which, depending on their length, can

examine greater proportions of the colon. Flexible

fiberoptic sigmoidoscopes (FSIG) are now available

in various lengths, 35 cm or 60 cm being the most

common; these generally can reach an average of 30

and 55 cm (12 to 20 inches), respectively, into the

colon. Full visualization of the entire colon is possible with a 180 cm colonoscope. The longer the

endoscope, the more technically difficult is the procedure, the greater is the risk of bowel perforation,

and the more intensive is the patient’s required

bowel cleansing preparation (116). Full colonoscopy

also requires patient sedation (164).

Prior to the development of flexible fiberoptic

colonoscopy, the ban-urn enema x-ray was the only

procedure available to inspect the entire colon for

tumors or polyps. Barium enema is a generic term

referring to radiological studies of the colon and

rectum using contrast materials injected into the

colon through the anus. The procedure has evolved

over time, and today the double contrast barium

enema (DCBE), which uses both contrast solution

and air to help visualize the colon, is the procedure

of choice (47,83,143,144). The barium enema is a

somewhat uncomfortable procedure whose accuracy

depends in part on the thoroughness of the patient’s

bowel cleansing preparation in the day or two prior

to the procedure (160). Its accuracy also varies with

the technical competence of the radiologist performing the study (47).

The fecal occult blood test (FOBT) indirectly tests

for the presence of CRCs or polyps by detecting

blood in samples of stool collected over three successive days. Many CRCs and some polyps become

ulcerated and bleed. If enough blood is present in
10- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

the stool, paper impregnated with the chemical

guiaic will turn blue when smeared with the stool

sample. The guiaic-based FOBT test will also turn

blue in the presence of other substances (90), particularly peroxidases present in some foods (93), and

intestinal bleeding may occur due to conditions other

than neoplasia, so that the test involves some false

positive results for neoplasia (56). Also, some CRCs

and most polyps bleed only intermittently or not at

all, so the test has a relatively high inherent false negative rate. Several variations of the FOBT are

available, some of which give quantitative results and

others which give only a positive or negative reading.

The most widely used test is the Hemoccult II (t.m.).

Newer tests for occult blood based on immunochemical techniques and heme-porphoroxal assays

have also been developed, but they are not in widespread use as screening techniques (7,51,129,130,

131,140).

RECOMMENDATIONS FOR

COLORECTAL CANCER SCREENING

IN THE ELDERLY

Numerous expert groups in the United States and

other industrialized countries have made recommendations about the periodicity with which the

elderly should receive particular colorectal screening

tests. The recommendations vary widely due to fundamental differences in interpreting the evidence on

the medical benefits, risks and costs of CRC

screening.

Recommending groups include professional

societies, voluntary health associations, governmentsponsored consensus panels, and third-party payers.

The discussion below first summarizes the positions

of major groups in the United States and then

describes the positions taken by government and

expert groups in selected industrialized countries.

Table 2 summarizes the recommendations for each

specific screening test.

All recommending bodies differentiate people at

low or average risk from those at increased risk of

CRC because of predisposing conditions or family

history. For high-risk people (e.g., those with one or

more first-degree relatives with CRC or people with

a history of CRC or adenamatous polyps) there is

general agreement that periodic surveillance

beginning some time before the age of 50 is prudent.

Low-risk individuals, defined mainly as young people

(under 40 years of age) without any high-risk conditions, should not be screened for CRC, according to

all groups. As people age, the risk of CRC increases

even for those without high-risk conditions; for these

“average-risk” individuals (over 40 or 50 years of age)

the recommendations of various groups differ widely.

The United States

The American Cancer Society (ACS) recommended in 1980 an annual digital rectal examination

beginning at 40 years of age and an annual FOBT

beginning at age 50. At age 50, two initial sigmoidoscopies each one year apart should be followed, if

negative, by subsequent sigmoidoscopies every 3 to 5

years. No age was suggested at which such screening

might be discontinued (2). In a 1988 update, ACS

left these guidelines unchanged (3), but ACS recently

revised the guidelines to require sigmoidoscopy every

3 to 5 years after age 50.

The National Cancer Institute (NCI) has

sponsored several panels and committees over the

past 10 years (155) to develop recommendations for

CRC screening (as well as for other kinds of cancer).

In 1985, in the course of developing public health

objectives for the year 2000, an NCI-sponsored committee could not agree on appropriate guidelines for

CRC screening and left this area without objectives

(37,96). More recently, NCI brought together

experts and interested organizations to develop

working guidelines for early detection of cancer; that

effort led in 1987 to the publication of working

guidelines for CRC detection. These are similar to

the ACS position. Specifically, the NCI guidelines

call for an annual FOBT and sigmoidoscopy every 3

to 5 years for average-risk people beginning at age 50

and continuing indefinitely. These guidelines were

approved by NCI’s Board of Scientific Counselors

and the National Cancer Advisory Board (NCAB),

(96) and have been incorporated into the NCAB’s

recent report (111). They are also being incorporated into NCI materials for public distribution

(159).

The American Society for Gastrointestinal

Endoscopy and the American Gastroenterological

Association have recently published recommenda-
Chapter 1--The Rationale for Colorectal Cancer Screening -11

Table 2-Recommendations for Screening for Colorectal Cancer In the Elderly

Country/ Screening recommendation by procedure

organization Digital rectal Fecal occult

(date of recommendation) examination blood testing Sigmoidoscopy

United States:

NCla (1987) Considered part of routine Annually Every 3 to 5 years

physical examination ————.— — ———————.——— — —————————— — — — —

ACSb (1989) Annually Annually Every 3 to 5 yearn —————————— — ——————— — ————————— — ————————— — ——————— —

ASGE & AGAC (1988) Frequency unspecified Flexible sigmoidoscopy

stating at 50, frequency

unspecified ——————————————— — ——————— — ————————— — ———————————— —

USPSTFd (1989) Digital rectal examination is not an effective screening maneuver, Task Force found

insufficient evidence to recommend for or against screening with fecal occult blood test or

sigmoidoscopy in asymptomatic persons, but notes it may be advisable to offer screening to

persons 50 and older with risk factors; Task Force does not specify what screening frequency

is optimal

Canada:

CTFe (1988) Not recommended unless Not recommended unless

specified risk factors specified risk factors

are present are present

Germany:

Governmentf (1977) Screening is suggested in

those over 45, frequency

not specified

World Health Annually Annually Every 3 to 5 years

Organization:

ABBREVIATIONS: ACS = American Cancer Society, AGA = American Gestroenterological Association, ASGE = American Society for Gastrointestinel Endoscopy, CTF = Canadien Task Force, NCI = National Cancer Institute, USPSTF = United States Preventive services Task Force.

a 

U.S. Department of Health end Human Sedcee, National Cancer Institute, Division of Cancer Prevention and tintml, Eerly Detection Branch, “Working Guidelines for Earty

Cancer Detection: Rationale and Suppotiing Eviderw to Decmeae Mortality,” Bethesd% MD, December 19S7.

b Americen ~~r society, “Summery of Cumnt Guidelines for the Mcer-Relatad Checkup: Recommendations” (New York, NY: ACS Professional Education Publication),

19s9.

C D, Flei~her, s, Goldberg, T Browning, et ~,, “Det-ion end Survei]lence of ~lorect~ Wcer,” JA.MA 261 (4):!580-565, 19S9.

d US, p-ntiw ~wi- T~k Fo~, GuM @ C\j~~ ~-s~ (Baltimore, MD: Williams & Wilkins, 19S9).

e ~~i~ peflodic He~h &emination T~k Force, “Eerty Detection of blorect/AI Cancer,” can. H. ASSUC. J. 141 :2Q9-216, 1989,

f F.W. Schwartz, H, Holstein, J.G. Brecht, “Preliminary Report of Fecal Occult Blood Testing in Germany,” in Ccdomcfai CerXXSC Pmentkrn, Epidamioiogy, end .Smening,

S. Winawer, D. Schottenfeld, end P. Shertock (eds.) (New York, NY: Raven Presa, 1980).

9 .S.J. Winawer, J. s John, J. Bond, et al., “Position Pepw Risk and Screening of Averege Risk Individuals for @lomctal Cancer,” forthcoming in WHO Bulletin.

tions for the detection of CRC that are consistent

with, though less precise than, the ACS/NCI

position. These two societies endorse FOBT and sigmoidoscopy for average-risk people beginning at 50

years of age but do not specify the frequency with

which such screening should occur.

In contrast to the recommendations of these

groups, the U.S. Preventive Services Task Force

(USPSTF), an expert group brought together under

the sponsorship of the U.S. Department of Health

and Human Services to investigate the appropriate

role of preventive services in health care, has recently

issued findings regarding both the FOBT and sigmoidoscopy. The USPSTF declined to recommend

either for or against periodic screening with either

FOBT or sigmoidoscopy in average risk individuals

45 years of age or older (80,133,157,158).

The Blue Cross/Blue Shield Association has

commissioned papers on the effectiveness and costs

of 10 selected preventive health services, including

CRC and has collaborated with the American

College of Physicians (ACP) to develop a

monograph scheduled for publication in 1990. Each

of the papers, one of which covers CRC screening,

19-753 0 - 90 - 2
12- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

will undergo peer review for publication in the ACP’s

journal, the Annals of Internal Medicine. ACP’s

Technology Assessment Committee is independently

reviewing each of the papers and will endorse the

papers’ recommendations as it deems appropriate.

For CRC, ACP has recommended annual FOBT and

sigmoidosocopy every 3 to 5 years for average-risk

individuals over the age of 50 (3a).

Other Countries

The USPSTF was modelled after a Canadian

Periodic Health Examination Task Force (CTF),

which issued its first report on preventive services in

1979, with several revisions since that time. In its

original report, the CTF recommended the use of

FOBT by asymptomatic people over 45 years of age

no more frequently than once a year (16). A recent

review of these guidelines led to a revision of CTF

findings. The Task force found that there is

inadequate evidence to recommend either for or

against screening for CRC, either by FOBT or sigmoidoscopy in a periodic examination of people over

40 with no known risk factors (17). Thus, the CTF

guidelines now match those of the USPSTF. This

result is not surprising, since the USPSTF had

adopted the CTFs criteria for assessing the evidence

on the effectiveness of preventive services.

The Federal Republic of Germany has provided

free annual FOBT screening for all people over the

age of 45 since 1977 (57,132). In contrast, the United

Kingdom’s National Health Service holds that at

present there is insufficient evidence of the effectiveness of any screening test in reducing deaths from

large bowel cancer and will not provide screening as

a service unless research currently underway shows

such an effect (24).

The World Health Organization (WHO) Collaborating Center for the Prevention of CRC at

Memorial Sloan-Kettering Cancer Center, which

WHO recognizes as its authority on CRC (82),

recommends annual digital rectal examinations

beginning at age 40, a stool occult blood test annually

beginning at age 50, and sigmoidoscopy every 3 to 5

years beginning at age 50 (174). These guidelines are

suggested for asymptomatic individuals in the context

of medical visits, not for general population

screening, although the difference between the two is

not clearly defined.

Understanding the Differences in

Recommendation

The differences among groups, and even within

groups over time, in recommendations regarding

CRC screening for average-risk people reflect two

facts. First, the evidence on the effectiveness of

specific CRC screening technologies is inadequate;

and second, the criteria (either implicit or explicit)

for judging the evidence that does exist differ among

the expert groups. At issue is whether a screening

test must be shown to reduce cancer incidence or

mortality in order to be considered effective, or

whether demonstrating a shift in the distribution of

detected cancers to earlier stages is sufficient for

considering a screening regimen effective. Those

who require direct evidence that CRC screening will

reduce the incidence of or mortality from CRC have

found the existing evidence inadequate. The critics

also point out that screening and diagnostic followup

have medical risks and high costs (22). Others focus

on the heavy burden of illness and death brought

about by CRC and conclude that even indirect evidence that screening may alter the course of a substantial proportion cannot be ignored (46,81).
Chapter 2

The Effectiveness of Colorectal Cancer Screening

ISSUES IN MEASURING

EFFECTIVENESS

To be judged effective, a cancer screening

protocol must either increase life spans, improve the

quality of life, or both. Changes in the length and

quality of life associated with a screening protocol

can be both positive and negative; the net effectiveness of a strategy would depend on how such

changes balance out. For example, if a positive

screening test result leads to risky or uncomfortable

confirmatory tests, the increased life expectancy and

decreased morbidity resulting from early detection

would have to be weighed against the increased

mortality, morbidity, or discomfort for those who

undergo the followup testing.

Accurate assessment of the full effects (both positive and negative) of a screening strategy requires

controlled experiments in which observed differences

in mortality and morbidity between those who

undergo screening and those who do not can be

validly ascribed to the screening program and not to

uncontrolled differences between the screened and

unscreened groups. When such studies are not

available, judgments about the importance of departures from full validity must be made, and studies of

more intermediate measures of effectiveness are

often used.

One intermediate measure of effectiveness commonly used in evaluating colorectal cancer (CRC)

screening is the positive predictive value (PPV), the

percent of all positive screening tests that lead to a

diagnosis of cancer or polyps. If the screening test

has a high false positive ratel

, the PPV will be low.

Even with a low false positive rate, however, if the

disease is rare, the PPV will be low, because the vast

majority of people who are screened will be disease

free and the number (though not the rate) of false

positive findings high. The PPV can also be expected

to decline with increasing frequency of periodic

screening, because the prevalence of previously

undetected cases would be lower in more frequent

screening programs. A low PPV implies that for

every cancer (or polyp) found, a large number of

people will be subjected to followup testing with its

inherent medical risks and costs.

Although it is a useful indirect indicator of effectiveness, by itself the PPV is insufficient. A screening

procedure with a low PPV can still be effective if the

reductions in mortality or morbidity resulting from

early detection are great compared to the morbidity

and mortality associated with the screening and followup procedures. Consequently, the use of PPV to

guide screening decisions involves implicit judgments

about the relative importance of a screening

strategy’s benefits and risks, which must be based on

other information.

Another measure of effectiveness often used in

evaluations of CRC screening is the stage-distribution

of cancers (or neoplasms) found. If a screening

program detects a high proportion of cancers relative

to the rate expected in the general population, particularly a high proportion in early stages with effective

treatment available, it is sometimes reasonable to

assume that this shift in the distribution of lesions

found toward earlier stages (or even toward precancerous stages) will ultimately be translated into

changes in mortality and morbidity, as fewer cancers

progress to more serious stages. Without additional

information, it is impossible to know to what degree

the increase in early-stage cancers (or precancerous

lesions) detected will actually translate into reductions in later cancers, because such studies are potentially biased in three ways:

o Lead time bias - the shift in cancer stage at

detection may reflect earlier diagnosis

unaccompanied by equal improvements in

benefit. Earlier detection of a completely

incurable cancer, for example, will improve survival time but will not help the patient. Indeed,

the patient may suffer unnecessary anxiety from

knowing early about a cancer with effective

therapy.

2 Because the length of time spent o Length bias -

in pre-clinical stages is longer for slow-growing

1The false positive rate is the percent of all people free of disease

whose screening test is positive.

%’his kind of bias has also been referred to as “overdetection”

bias (116).

-13-
14- Costs and Electiveness of Colorectal Cancer Screening in the Elderly

lesions than for fast-growing lesions, slowgrowing lesions have a greater chance of being

detected in a periodic screening program.

These slow-growing lesions are not as invasive

or lethal as fast-growing cancers. Thus, the

stage shift will overestimate the number of late

cancers averted or the years of life gained.3

o Volunteer bias - people who agree to participate

in screening (or even in a cancer screening

trial) may have a different clinical course from

those who do not, possibly leading to a different distribution of cancers found by

screening.

In addition, reliance on the shift in the stage distribution of detected lesions as the principal indicator

of effectiveness ignores the medical risks and

inconvenience of the screening and followup testing

required to find the early cancers.

The problem with stage-specific case finding rates

as measures of effectiveness is even greater if the

focus is on colorectal polyps, the suspected

precursors to cancer. Since only a small minority

(perhaps 5 to 10 percent) of colorectal adenomas

progress to cancer (106), the potential impact of

length bias is even greater, and screenees will be subjected not only to the medical risks of followup

testing, but also to the risks of removal of many

polyps that would not have progressed to cancer.

Because of these problems, most experts would

agree that fully valid evidence on the effectiveness of

any CRC screening program requires randomized

clinical trials comparing mortality and morbidity

rates in those offered screening with such rates in

those not offered screening (39,157,158). Such

studies are difficult and costly to mount, however.

CRC is relatively rare and takes as long as 10 to 15

years to progress from polyps to clinically detectable

stages (106), so that measurement of the effects of

screening requires many participants and many years

to follow the medical histories of study subjects.

Despite these problems, several well-designed

studies of selected CRC screening protocols are currently underway and may in time provide highly valid

information on the effectiveness of certain colorectal

screening protocols.

The inadequate evidence on the net effectiveness

of CRC screening underlies the present disparity

among experts in conclusions about the appropriate

place of CRC screening in average-risk older adults.

Those who require high standards of validity in

studies of screening techniques generally conclude

that no CRC screening protocol has been shown to

be effective (48,49,50,116,133,137). Others who

examine the shift in the distribution of lesions found

to early or precancerous stages have concluded that

the potential biases are unlikely to account for all of

the benefit afforded by early detection (35,171).

Eddy has observed that “There is a conceptual issue

here -- how certain do you have to be before you say

it is beneficial?” (81).

EVIDENCE ON EFFECTIVENESS OF

FECAL OCCULT BLOOD TEST (FOBT)

Although a large literature exists on the use of

the FOBT as a strategy for CRC screening, only six

controlled studies of FOBT screening in asymptomatic individuals have been reported, and four of

these are still underway. 4 The researchers in each of

these studies have reported the PPV of the FOBT

and most have studied differences between the intervention and control groups in the stage of cancers

detected. Interim mortality data are available from

only one study, a large ongoing study of FOBT

screening in a community in Denmark begun in 1985.

Table 3 summarizes the study designs and results of

the trials to date.

All but one of the studies are large randomized

clinical trials conducted in older average-risk individuals, beginning at ages 45- to 60-year-olds. The

exception is a study of volunteers over 40 years old

attending a cancer prevention clinic in New York

City who were assigned to experimental and control

groups according to the month in which they presented at the clinics

3An even stronger argument can be made with respect to

screening and removal of colonic polyps. If the cancers that tend

to progress rapidly are not those arising from polyps, then

removing a large number of polyps may not have much effect on

the incidence of cancer (101).

4For reviews of uncontrolled studies of FOBT screening, see

Simon (137); Frank (48,49,50); and Fletcher and Dauphinee (46).

5

In this trial, both groups received sigmoidoscopy as part of a

cancer checkup. Only the experimental group received FOBT.
Chapter 2--The Effectiveness of Colorectal Cancer Screening- 15

All six studies have reported on the PPV for

cancer, adenomatous polyps, or neoplasms (cancer

+ adenomas). As discussed above, the PPV for a

specific condition is directly related to the prevalence

of the sought-after condition in the screened population and inversely related to the false positive rate.

The prevalence of previously undetected disease

would decrease as screening frequency increases;

therefore, programs with more frequent screening

intervals should have lower PPVs. Also, the first

screen in a new FOBT screening program should

have a higher PPV than subsequent screens. Thus,

studies undertaken for longer periods of time, with

periodic rescreening, should report lower PPVs

overall and declining PPVs as the trial progresses.

These trends are apparent in the studies. The University of Minnesota study has had the longest period

of screening (at 1- and 2-year intervals) and has

reported the lowest PPV for FOBT, only 2.5 percent

for cancer (i.e., a positive FOBT resulted in a cancer

diagnosis less than 3 percent of the time). The other

controlled studies reported PPV for cancer on first

and second screens in the neighborhood of 10 to 20

percent.

Because PPV depends on prevalence, it should be

higher in populations with higher prevalence of CRC.

Where data on PPV are available by age, the results

are consistent with expectations. In the Strang Clinic

study, the PPV for cancer in screenees 70 years of

age or older (23 percent) was almost twice as high as

the PPV in the screened population as a whole (170).

The method of preparing FOBT specimens for

analysis also affects the PPV because it alters the

false positive rate. Dehydration (adding a few drops

of water to the test slide prior to analysis) is frequently practiced to increase the test’s sensitivity to

blood in the stool. But dehydration also increases the

false positive rate. Consequently, the PPV of FOBT

under dehydration is lower than the PPV without

such a procedure. The Swedish study showed that

dehydration reduced the PPV for all neoplasms by 10

percentage points. Dehydration of test slides was

gradually introduced in the University of Minnesota

study in order to increase test sensitivity; in all,

approximately two-thirds of all slides were

dehydrated. Thus, the low PPV in that study may be

partly due to dehydration.

Because the prevalence of adenomatous polyps is

much higher than the prevalence of cancer, particularly in elderly people, the PPV is substantially

higher for neoplasms than it is for cancer alone. In

the Danish study of biannual FOBT screening in 45-

to 70-year-olds, 52 percent of all positive FOBTs

were diagnosed either with a cancer or adenoma,

compared to 7 percent for cancer alone. Among 60-

to 64-year-olds in Sweden, the PPV for neoplasm

(i.e., cancer plus polyps) with dehydrated slides on

the second screen was 24 percent. Ransohoff and

Lang have observed that the calculated PPV of the

FOBT may actually reflect a random selection of

elderly people for followup and detection of their

polyps. To the extent that false positive FOBTs

occur serendipitously in patients who happen to have

polyps, the PPV will give the FOBT credit for

“finding” the polyp even though it occurred by chance

(123).

The success of an FOBT screening program in

detecting early cancer or altering mortality rates

depends in large measure on the rate of compliance

with screening regimens in the population. If few

people avail themselves of the opportunity to be

screened, then the potential for detecting and

treating cancer early is compromised. Compliance

appears to vary widely across the studies, depending

on the age of the screenee (older people are less

compliant); the age of the program (compliance with

rescreening is lower than with the first screen); the

population on which randomization was based

(volunteers are more compliant, at least in the

beginning); and the kinds of recruitment efforts

made by the program.

Despite imperfect compliance, rates of detection

of CRC are consistently higher in the intervention

groups than in the control groups, and a higher proportion of those found are early cancers. For

example, an ongoing British trial begun in 1984

found 58 percent more cancers in the group offered

screening than in the control group after 2 screening

periods. These extra cancers detected were heavily

concentrated in Stage A, the most curable stage of

CRC. The Swedish study also found a much higher

rate of cancers in the intervention group after 27

months of study, but differences in the distribution of

cancer stage, which favored earlier cancers, were not
Table 3-Fecal Occult Blood Teat (FOBT) Controlled Clinical Trials

Intervention Control Screening Dehydration FOBT positive Cancer stage

Study/site Years Study population group(s) group compliance rates status predictive value et detection Mortality

Strang Clinic 1975-1079

Colon Project,

New York,

NY a,b,c

————————

Funen, 1985-

Denmark d,e ongoing

—————— ——

Hardcastle, 1983

Nottingham,

Englandf

21,008 symptomatic

volunteers › 40 years

old (33% › 60)

attending cancer

prevention clinic and

followed up in 1984

——————

60,00045 to 70-

year-olds

asymptomatic for

colorectal cancers,

adenomas, or

metastasis from all

cancers

Annual medical Same as 60-80% compliance Unspecified, PPV on all screens

exam, rigid intervention in year 1, declining to but most No [initial + followup):

sigmoidoscopy and except no 20-40% in year 5

FOBT (group

selected by calendar

period of entry to

clinic (Hemoccult and

Tot PPV:

12% for cancer

36% for cancer +

adenomas

Hemobcult II) PPV (60-69 years old)

13% for cancer

42% for cancer +

adenomas

PPV › 70 years old)

23% for cancer

42% for cancer +

adenomas —————————— — ——————— — ————————— —

Randomized: No First screen: No First screen:

30,000 offered screening 65-69 70-74 18% cancer

screening every 2 offered men 63% 54 % 58% cancer +

years with reminders women 64% 50% adenomas

Second screen:

7% cancer

52% cancer +

adenomas

——————— ————————— ————————— ——————————

20,525 patients 45 to Randomized: No 35.1% men No 52% neoplasm

74-year-olds in 9 10,253 sent screening 34.8% women

general practices in instructions on 27% for › 70 year

Nottingham, England Hemoccult II

without known bowel

disease or cancer

Percent of all cancer detected in NA

Dukes’ A and B:

65% in intervention group

33% in control group

—————————————————

Rate of CRC detection after 34 months

Test grp Control grp

All CRC 0.428% 0.306% (p<0.01)

Stage A CRC 0.122%0 002% (p‹0.0001)

Other Stages 0.204% 0.286% (p<0.002)

First 38

months of

Study:

27%

reduction

in CRC

mortality,

not

statistically

significant

(p=0.16) ————— . ———— — ————— —

Rate of CRC detection NA

Test grp Control grp

All CRC 0.225% 0.097%

Stage A CRC 0.092% 0.000%

ABBREVIATIONS: CRC = colorectal cancer FOBT = fecal occult blood test; NA = not available; NS = not significant; PPV = positive predictive value.

a B J Flehinger, E. Herbert, S.J. Winawer et al., “Screening for Colorectal Cancer With Fecal Occult Blood Test and Sigmoidoscopy: Preliminary Report of the Colon project of Memorial Sloan-Ketting Cancer Center and PMI-Strang

Clinic,” J Chamberlain and A.B. Miller (eds.) Scmerrhrg for Gastrdnk@fnd Cenoer (Lewiston, NY: Hans Huber Publishem, 198S).

b SJ Winawer, M, ~dwin, E, l+erbedet~., “screening& perienceWith Fecal Occult Blood Testing asa Function of Age,” in%mpedkson%wrrtbnand 7/B8fme17tOf CWicW h thet%terfy, R Yancik, P.P. Cat’bone, W.B. Patterson

et al. (eds.) (New York, NY: Raven Press, 19S3).

c S,J, Winawer, J St. John, J. Bond et al., “Position Paper: Risk and Screening of Average Risk individuals for Coiorectal Cancer,” forthcoming in WHO Bul%ffn.

d o Konborg, C. Fenger, 0. Sondergaard et ~, “Initial Mass Screening for Colorectal Cancer With Fecal Occult Blood Test,” Sand. J. GasfroenteroL 22:677-6S6, 10S7.

e 0~onborg,‘M-screening for colorect~ WCer With Hemoccult-11 at Funen in Denmark,” Interim Report, June 19SS, unpublished.

f J,D H~d~~le, p,A, F~r~dsr T,W. ~our et ~,, “~ntroiied Testing in the Detection of Giorectd cancer,” ~8nCd2:l-4, 19S3.

g J.D. I-kmfca$tle, “Randomized Controlled Trial of Fecal occult Bid: Screening for Coloredai Cancer,” unpublished paper, no date.

h Js Mandel, J.H. Bond, M Bradieyetal,, “Sensitivity, Specificity and Positive Predictivityofthe HemoccuttTeet in Screening forcolorectal cancers: The Univereityof Minnesotans COIOn Cs#_i@r Control Study,” unpublished -r,

i undated.

J S Mandel, J.H Bond, D C Snover et al., “screening for Coiorectal Cancers: The University of Minnesota’s Study,” unpublished paper, undated.

j J.S Mandel, Llnivereity of Minnesota, personal communication, Ju~, 1~.

k K, ~~rg, M,s M~sen, 0, sonderg~d et ~,, “p~ici@ing in M= screening Colorectal &ncer with Fecal occuR Blood Test” Scarxf. J. GSStToWlf. 21:1 1S0-1 1S4, 19S6.

I J, ~enter, s, Bjo~,E,Hqlind@~,,.~r~ning~d Rescreening for colorect~ ~cer: A ~ntrolled Tri~ of Fe@ oCCUtt Blood Testing in 27,700 Subjects,” C~ 62(3):645651, 19SS.
Table 3-Fecal Occult Blood Teat (FOBT) Controlled Clinical Trials (continued)

Intervention Control Screening Dehydration

Study/site

FOBT positive

Years Study population

Cancer stage

group(s) group compliance rates status predictive value at detection Mortality

Hardcastle, 1984-

England g ongoing

University of 1070-1982

Minnesota g,h,i (phase 1)

1986 -

(phase II -

ongoing)

107,000 50 to 74- Randomized: No

year-olds 53,464 offered screening

A) 3day

Hemoccult II

B) 6-day

Hemoccult II

with reminder;

positive tests repeated;

rescreen at 2-year

intervals offered to

those accepting first

screen ———.——— — ———————— —

46,622 volunteers Randomized: No

aged 50-80 recruited 1) annual FOBT screening

from community 2) biannual FOBT

——————.— —————————————————

Gothenberg, 1982-1983; 27,503 residents of Randomized: No

Sweden k,l 1984-1985; Gothenberg aged First screen – screening

and 60-64 in 1982 mailed

ongoing Hemocult II

with mail return &two

reminders

1) dehydrated

2) not-dehydrated

Second screen –

dehydrated only

Initial screen: 52.9% No Initial screen:

First rescreen: 77.0% 10% for cancer

Second First rescreen:

rescreen: 80.0% 8% for cancer

Second rescreen:

12% for cancer

All screens:

10% for cancer

————————————— —————

Phase I (1976-1982) No/Yes 1st phase:

1) 75.7% (gradually 2.5% cancer

2) 76.7% introduced 16.2% adenomatous

declined preciplously during polyps

for those ›80 years phase i)

old (@ 55%)

< 6 0 = 1.690

overall,

————————————————— —

First screen: First screen: First screen:

66% random Dehydrated –

Second screen: allocation of 22’% for neoplasms

58% specimens Not dehydrated –

to 32% for neoplasms

dehydration Second screen:

and no 24% for neoplasm dehydration;

on second

screen

dehydration

only

Rate of CRC detection after 2 rescreens NA

Teat grp Control grp

All CRC 0.33% 0.22% (p<.0.01)

Stage A CRC o 10% o 02% (p<.0.01)

Other Stages CRC 0.23% 020%

—————————————————

Percent of all CRCs detected in Stage A NA

in screen group: 35%

—————————————————

Rate of CRC detection after 27 months NA

Test grp Control grp

All CRC 0.44% 0.15% (p<0.001)

Stage A 0.09% 0.02% (NS)

Stage B 0.1 1% O 04% (NS)

(C& D) 0.24% 0.09 (NS)

ABBREVIATIONS: CRC = ooloreotal canoq FOBT = feoal occult blood test; NA = not available; NS = not significant; PPV = P08itw predictive value.

a BJ, F~i~r, E l+e~,, SJ, Winawer@~,, ‘~r~ningfor~lor~~ ~~rwhh Fw~ulfBloodTestand Sigmoidoecopy: Preliminary Report of the Colon proj~of Memofi~ Sloan-~erin9 c~~r~nter~d pM1-Str~g

Cihtk,” J. Chamberlain and A.B Miller (eds.) Sorsren/ng for Gaafmhte.sfindCan oer(Lewiston, NY: Harrs Huber Publishers, 198S).

b SJ, W\n~, M, -in, E. He~rt~~., “W~ning @@enceWith F@ Occult Blood Testing aaa Funotionof Age,” in%speohwson Prevw@nand Treafnmrrtof CanoerlntheElderfy, R. Yancik, P. P. Carbine, W.B. Pattereon

@ al. (eds.) (Nsw York, NY: Raven Press, 19S3).

c SJ. Winawer, J. St. John, J Send et al., “Position Psrpsm Risk and Screening of Average Risk Individuals for Colorectal Cancer,” forthcoming in WHO Bulletin.

d 0, ~~, c Fenwr, 0 sorlderg~ ~ ~,, “inni~ Ma sor~nirlg for ~ior~~ ~~rwnh Fecal Occult Bid T~,” SoWRY. J.~~ 1. 22:677-8s6, 1BS7.

.0 ~~g,‘Mm ~r~rlingfor @IOW~~r wnh Hemmuti-11 d Flmen in @rrmark,” Interim Report, June 19SS, unpublished.

f J.D. ~b, P.A. Farrands, T.W. Baifour et al., “Controlled Testing in the Deteotion of Colorectal Canoer,” Lanoet 2:1-4, 1983.

g J.D. Harc@stb, “Randomized Controlled Trial of Fecal Oooult Biood: Soreening for Coioreotal Carroer,” unpublished paper, no date.

h J.S. Mandei, J.H. Bond, M. Bradleyet al., ‘Sensitivity, Specificity and Poeitive Prediotivifyofthe t+emoocult Teef in Soreeningfor Coloreotal Grwers: The University of Minnesota’s Coion Canoer Control Study,” unpublished paper,

Urldstcd.

i J.S. Mandel, J.H. Bond, D.C. Snover et al., “Screening for Coloreotai Cwwere: The University of Minnesota’s Study,” unpublished paper, undated.

I JS,-iIJn~re~ofMinn~~ personal oommunioation, July, 1~

k ~,d,M,s, Mad-,0, ~derg~d @ ~,, ‘p~icipirlg in MSSS &~ning tilorectal Canoer Wnh Fecal O@uIf Blood Tx” ~. J. Gaafroenf. 21:11s0-11s4, 1SS6.

i J, ~~r, s, Bj~, E, -li~ @~, •~r~ning and R~r~ning for ~ior~~~~ A @~rOil~Trial Of FMA OcoUn Blood Testing in 27,700 Sub@t8,” C~ 62(3):645651, 1sss
18- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

statistically significant. The Swedish study is much

smaller than the British trial, however, which may

account for the lack so far of statistically significant

differences in cancer stage distribution.

Only one of the trials has reported on mortality

differences between intervention and control groups.

A large trial of biannual FOBT screening of 45- to

70-year-olds in Denmark found a 27 percent lower

CRC mortality rate in the group offered screening

after about 3 years of study, but the number of

deaths in the study so far is very small and the difference is not statistically significant by conventional

standards (p = 0.16).

To summarize, the six controlled studies of

FOBT screening suggest that in an ongoing screening

program, a large number of screenees will undergo

followup diagnostic tests for every CRC found, but

this number decreases with the age of the screenee.

It is clear that FOBT screening improves the stage

distribution of cancers detected, which should

translate into decreases in cancer mortality.

However, even in very large trials, no such mortality

effect has been identified to date. This leads to the

possibility that length bias may have a strong

influence on the screening programs.

EVIDENCE ON THE EFFECTIVENESS

OF SIGMOIDOSCOPY

The argument for effectiveness of sigmoidoscopy

as a screening tool is most forcefully made through

direct comparison with the FOBT. Unlike the

FOBT, which has many false negatives for cancer,

sigmoidoscopy has high sensitivity and specificity for

rectal or colonic lesions within its reach into the

colon. Indeed, endoscopic examination is the diagnostic standard against which most other CRC

detection methods are assessed (133). In studies

comparing sigmoidoscopy with barium enema, sigmoidoscopy generally had a very high sensitivity -- on

the order of 90 to 95 percent in detecting lesions

found by either method in asymptomatic or symptomatic persons (148,167).

Because polyps and cancers are directly visualized

in sigmoidoscopy, a positive finding is always a true

positive. The virtual non-existence of false positives

would imply a high PPV for sigmoidoscopy. If,

however, one considers some of those positive

findings to be clinically insignificant, then sigmoidoscopy may have a substantial false positive rate

and, hence, a lower PPV. Hyperplastic polyps, for

example, do not progress to cancer, but it is

impossible to accurately differentiate hyperplastic

polyps from neoplastic polyps without a biopsy. Consequently, when such polyps are found they are typically removed and biopsied. The clinical significance

of very small polyps (i.e., those smaller than 5 mm) is

also questionable (106); some researchers believe

that these are highly unlikely to progress to cancer,

yet they, too, are typically removed when found on an 6 Thus, for every “positive” endoscopic examination.

sigmoidoscopic screening examination, a relatively

small number may actually be at risk for developing

into CRC.

The rapid change in endoscopic technology that

occurred in the mid-1970s increased the tension

between detection capability and clinical significance

of lesions detected. The development of flexible

fiberoptic sigmoidoscopes with lengths of up to 60

cm, compared to the 25 cm length of the rigid sigmoidoscope, increased the potential proportion of

polyps and cancers that are detectable with high

sensitivity and specificity with sigmoidoscopy at the

same time that it increased the number of clinically

insignificant lesions found and removed. A review of

studies comparing flexible with rigid sigmoidoscopes

found about 2.6 times as many cancers and 2.5 times

as many polyps with a 60 cm flexible sigmoidoscope

as with a rigid sigmoidoscope (76).

Studies of the impact of sigmoidoscopic screening

on cancer incidence or mortality are even fewer than

for FOBT. Only three studies of outcomes of

screening programs using sigmoidoscopy have been

reported and all used the rigid sigmoidoscope. Two

of these were long-term observational studies of

screened subjects without comparison groups. The

third was a randomized clinical trial of rigid sigmoidoscopy as part of a program of periodic preventive health services offered to non-elderly

%his position is controversial. Tedesco found that alInost50

percent of very small polyps were adenomatous, but the study

was in a symptomatic group of people (147).
Chapter 2--The Effectiveness of Colorectal Cancer Screening- 19

enrollees in an HMO. These studies have been carefully reviewed and critiqued by several experts

(101,116,133).

The two observational studies of CRC sigmoidoscopy screening programs showed dramatic

shifts of detected cancers to early stages. A study of

annual sigmoidoscopy examinations offered from

1946 to 1954 at the Strang Clinic in New York to

26,126 patients 45 years of age and older, most of

whom (89 percent) were asymptomatic at the time of

sigmoidoscopy, detected 81 percent of CRCs in Stage

A or B (67). In a study of annual sigmoidoscopy

offered to people 45 years of age and older in Minnesota between 1948 and 1974, all cancers detected

on the second or subsequent screens were in stage A

or B (54).

An analysis of cancer incidence and mortality in

the Minnesota program’s followup period suggested

that, after eliminating cancers found on the first

screen, the rate of CRC detected in subsequent years

was much lower than would be expected in a like

unscreened Minnesota population (54). This would

imply that removal of polyps found on sigmoidoscopy

prevented CRC. But the cancers found at the first

screen were not prevented; rather they were found

early (101,105,114,133). In a reanalysis that included

pre-existing cancers, Miller concluded that the CRCs

detected over the period were strikingly similar to

the age-adjusted rate in an unscreened population

(101). Selby and Friedman have also pointed out

that the reported incidence rate in the screened

group was based on the number of person-years of

observations, and people may have dropped out of

followup if CRC was discovered. Thus, the actual

CRC incidence rate in the population offered

screening was probably higher than reported in the

study (133). Finally, as a program that enrolled

volunteers, the cancers in the Minnesota study may

have had an unrepresentative incidence and stage

distribution (114), although the direction of such

“volunteer bias” cannot be predicted.

The one randomized clinical trial involving

annual rigid sigmoidoscopic screening for 40- to 54-

year-olds as part of a multiphasic health examination

for enrollees in an HMO found significantly lower

death rates from CRC over an n-year period in the

group offered screening than in the control group

(27). On its face, this finding from a randomized

trial would be strong evidence of an effect on

mortality from sigmoidoscopy. But several

reviewers, including one of the investigators on the

original study, have called these results into question.

First, the difference between the study group and

control group in the use of sigmoidoscopy over the

10 year period (31 percent vs. 26 percent) was not

great enough to account for the two-fold observed

difference in CRC mortality (133). Second, most

tumors found in both groups were detected from

symptoms, not through screening (133). Third, given

the design of the study, the authors probably used

too lenient a test for statistical significance (101,

114,133). Thus, several reviewers have concluded

that whatever real differences existed in CRC

incidence and death between the study group and

control group were due to factors other than the

availability of sigmoidoscopy (101,114,133).

Taken as a whole, the evidence on sigmoidoscopy

suggests a major shift in the stage at which CRCs are

detected, but inadequate evidence that this stage shift

actually reduces death rates from cancer over time.

How can these two seemingly contradictory findings

be reconciled? First, there has never been a good

trial of the effect of screening flexible fiberoptic signodoscope (FSIG) on cancer mortality, so the lack of

evidence on outcomes should not be equated with

the existence of negative evidence. But, second, if

future randomized studies do confirm that stage shift

is unaccompanied by changes in mortality from CRC,

then one must look for possible biases in screening

programs. Only if therapy is no more effective in

early cancers than in late cancers or if length and

volunteer biases are strong can the stage shift

coincide with no impact on mortality. Experts agree

that therapy is much more effective in early CRC

than it is once cancer has spread beyond the wall of

the colon or rectum (23,145). Thus, increased lead

time would not explain the lack of mortality differences between screened and unscreened groups.

Many experts believe that length and volunteer

biases can be powerful influences on outcome and

consequently discount the evidence on stage shift as

inadequate. Others see the dramatic shifts in stage

at detection as unlikely to be caused simply by length
20- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

and volunteer bias; they accept this evidence as sufficient to justify periodic CRC screening with sigmoidoscopy or FOBT.

Virtually all CRCs are removed promptly after

detection, so there is no direct evidence on how the

length of time in each stage of cancer varies among

patients. If the distribution of time spent in early

stages is very wide, with some cancers progressing

rapidly but many progressing slowly or hardly at all,

then the case for length bias is strengthened.

Numerous experts have commented on the high

variability in the speed with which cancers grow in

size or progress (29,145). Periodic screening would

be likely to pick up relatively few of the rapidly progressing cancers (a high proportion of which would

develop and grow in the time interval between

screenings) but a large number of indolent cancers.

On the other hand, if all CRCs progress at a similar

speed, then the argument for length bias would be

weaker, and the evidence on the proportion of early

cancers detected would be compelling. Because it is

unethical to leave CRCs detected but untreated,

direct observation of the distribution of cancer progression rates is infeasible; only controlled cancer

screening trials of sufficient size and duration will

provide definitive information on the extent of length

bias. The National Cancer Institute (NCI) has

recently announced plans for a 5-year randomized

clinical trial of sigmoidoscopy screening in men 60-

to 74-year-olds (152). This trial, which will enroll

enough men to detect a 20 percent decrease in

mortality, will test whether a sigmoidoscopy every 3

years will affect outcomes in the elderly. The results

of the trial will probably not be available for at least

10 to 15 years.

EFFECTIVENESS ISSUES SPECIFIC

TO THE ELDERLY

Although all CRC screening programs have

targeted older people (generally over 45 or 50 years

of age), screening in the elderly (people 65 years of

age and older) raises issues that may not be so

important in middle-aged people.

High Incidence of CRC in the Elderly--The

incidence of CRC rises dramatically with age (see

Chart I); the incidence of CRC at ages 70-74, for

example, is 5.7 times higher than at ages 50-54 (152).

At the same time, it does not appear that CRC progresses at a different rate in the elderly; the distribution of stage at detection is virtually the same in

the elderly as in the non-elderly (58,73,75,104).

Thus, the potential burden of illness in those over 65

years of age is much higher than for other groups,

and the potential effectiveness of screening in

reducing morbidity and mortality is higher as well.

The distribution of cancers throughout the large

intestine appears to be different in the elderly. The

elderly tend to have more CRC located proximal to

the splenic flexure than do the non-elderly

(45,63,139). In a Swedish study of 264 patients with

polyps found through colonoscopy, polyps in patients

over 65 years of age were much more uniformly distributed throughout the large intestine than were

polyps found in people 55 years of age and under.

There, almost 70 percent of all polyps were found in

the sigmoid colon and rectum, compared to only

about 35 percent of polyps in the elderly (59,161).

Consequently, within their limited reach, sigmoidoscopes would probably detect a smaller fraction of all

CRCs in the elderly than in non-elderly screenees.

High Prevalence of Colorectal Polyps in the

Elderly--The prevalence of asymptomatic benign

adenomatous polyps increases dramatically in the

elderly. Autopsy studies conducted in the United

States and other countries over the years have consistently found an increase in the prevalence of

polyps with age up to approximately 60- to 70-yearolds. Beyond that point, the prevalence of polyps

shows no systematic relationship to age (table 4).

Although the frequency of adenomas increases

dramatically with age, the average size of these

lesions does not vary with age, which suggests that

“while new adenomas develop with aging most tend

to remain static in size after reaching a diameter of

less than 10 mm” (128).

If adenomas are precursors of the vast majority

of CRCs, as many researchers have suggested

(25,35,106,108), then removal of adenomas would

appear to be prudent even if the great majority of

them will not develop into cancer, but this would

imply that a large number of elderly people entering
Chapter 2–The Effectiveness of Colorectal Cancer Screening- 21

Table 4-Age-Specific Polyp Prevalence: Autopsy Studies

Age-specific prevalence rate (number)

60-69 70-79 80 and over

Study Year population Polyp type Male Female Male Female Male Female

United States:

Rickert et al., NG 518 autopsies of Adenomatous 59.8% 48.8% 68.996 40.0% 61.1% 63.0%

1979 males and females (58) (19) (51) (20) (22) (17)

between ages 20 and

102 not previously

diagnosed with carcinoma of the bowel

——————— — ——————————————————.— — ————————————————— —

Stemmermann 1960-1972 Autopsies from 202 Adenomatous 60.0% 59.0% 70.0% 60.0% 66.0% 83.0%

and Yatani, Hawaiian Japanese (22) (10) (16) (18) (23) (12)

1973 at the Kuakini hos- Hyperplastic 81.0% 77.0% 87.0% 67.0% 86.0% 16.0%

pital in Honolulu, HI (30) (13) (20) (21) (30) (16) ——————— ——————— ——————— ——————————— — ————————————— —

Arminski and NG 1,000 autopsies of Adenomatous 39.9% 25.3% 46.1% 47.3% 46.3% 42.5%

McLean, 1964 men and women aged (79) (28) (53) (35) (19) (17)

20 and over at the

Grace Hospital,

Detroit, Ml ——————— ——————— ——————— ————.—— ——————— ——————————— —

Chapman, 1963 NG Autopsies of 443 Adenomatous 43.0%a 37.0% 65.0% 37.0% 63.0% 50.0%

adults in New York (NG) (NG) (NG) (NG) (NG) (NG)

hospital ——————— ——————— ——————. ———.——— ——————-——————— —

Blatt, 1961 1960 556 autopsies per- Adenomatous 35.0% 37.5% 45.0% 46.0% 46.7% 40.0%

formed during a (23) (15) (42) (29) (21) (20)

9-month period

in NY (446 colons

used in the study) ——————— ——————— ——————————————— —

Correa et al.,

———————————— —

1970-75 301 autopsies per- Hyperplastic 14.3% b 10.4% b

1977 formed in New (177) (124)

Orleans

Other countries:

Williams et al., NG 365 autopsy specimens Adenomatous 44.0%d 35.0% 52.0% 33.0%

1982 in a l-year period (25) (18) (22) (21)

in Liverpool, England. Hyperplastic 47.0% 13.0% 33.0% 34.0%

134/365 came from cases (27) (7) ( 14) (22

dying in hospital. ——————— ——————— ——————— ——————— —————————————— — ——— —

Restrepo et al., 1971-1973 529 specimens from Adenomatous 7.0%

b 16.7%

1981 consecutive autopsies (32) (24)

of persons age 10 and Hyperplastic 31,2% 29.2%

over in a hospital in (lo) (7)

Medellin, Colombia ——————— ——————— ——————— ——————— ——————————————— —

Hughes, 1968 1964

— — —

200 colons from Not Specified 22 %

C 17% 32.4%

autopsies done in (10) (11) (12)

Queensland, Australia

examined for polyps

NG = not given.

a In this stu~ groups ens divided at age 65 to 74, 75 to ~, Md ~ ad o~r.

b In this study the prewdence rate for eldedy people is reportad as one group, we m ad o~r.

c M~e ~d km~e prwaJencis rates are combined.

d tn this etudy groups are divided at age 65 to 74, and 75 mcf over.

SOURCE: T.C. Arminskl end D.W. McLean, “Incidence and Distribution of Adenomatous polyps of the Colon and Rectum Baead on 1,000 Autopsy Examinations,” f)is. ColorI

Rectum 7:249-261, 1964; LJ. Blatt, “Polyps of the Colon and Rectum: Incidence and Distribution,” C#s. Ccl. Rec. 4:277-2S20 1961; 1. Chapman, “Adenomatous Polyplof

Large lnteatine: Incidencearrd Distribution, ”Ann. Surg. 157(2):223-226, 19S3; P. Co~J.P. Strong, A. Reif, et al., “The Epidemiologyof Coloreotsd polyps: Prevalence in

NewOrfeansand lntemational Comparisons, ‘Car)cer3S:225S-22S4, 1977; LE. Hughes, “Thelncidenoeof Benign and Malignant NeoplasmsoftheColon and Rectum: A

Post Mortem Study, ”/V.Z. J. Surg. 3S(1):30-35, 19SS; C. Restrepo, P Co- E. Duque, et al., “polyps ina Low-Risk CoIonic Population in CoIumbix South America. ”fXs.

Cokm Recfum, 24:29-3S, 19S1; R.R. Rickert, O. Auerbackk, L Garfinkel, et al., “Adenomatous Leaions of the Large Bowel: An Autopey Survey,” Cenm3r43:lS47-lS57,

1979; G.N. Stemmerman and R. Yatani, “Diwsrticulosisand Polypaofthe Large Intestine: A Neocropsy Study of Hawaii Japanese, “ Oancer31 (5):1260-1270, 1973; A.R.

Williams, B.A. Balasoorty~ D.W. Day, et al., “Polyps and Cancer of the Large Bowel: A Necropay Study in IJverpool,” Gut 23:S35-S42, 19S2.
22- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

a screening program for the first time would have

one or more polyps removed, with consequent risks

and costs. In addition, with FOBT and sigmoidoscopy as the screening tools, elderly people

would not be likely to have as high a proportion of

polyps found and removed as would the non-elderly,

mainly because more are located beyond the reach of

the sigmoidoscope and are not likely to be picked up

by the FOBT. If the detection and removal of polyps

are important for the success of a CRC screening

program, then perhaps a screening tool with greater

sensitivity and reach into the colon, such as DCBE or

colonoscopy, would be more effective (but also more

costly) in the elderly.

Decreased Acceptability of Screening Procedures--There is some question as to whether the

elderly find the current screening methods

acceptable. The discomfort of sigmoidoscopy and

the preparation required for all screening, including

dietary restrictions, purging, etc. may be more difficult for elderly people to undertake than younger

people.

Increased Fragility in the Aged--The ability of

elderly people to withstand the discomfort and risks

of sigmoidoscopy and colonoscopy is highly variable,

of course, but the issue of increased complications

with age needs to be considered. The elderly tend to

have more underlying diseases that may make it

more difficult to pass these instruments (135), and

rates of post-colonoscopy hemorrhage may be higher

in the elderly than in the non-elderly (30). In

addition, the dietary preparation needed both for

adequate endoscopy and DCBE may be more difficult for frail or very old people to withstand (135).

Especially in the very elderly (those 80 years of age

and above), the question must be asked how much

morbidity is associated with the screening tests themselves and any followup procedures, such as the

DCBE, colonoscopy, or surgery (120). Studies of

resection for CRC in the elderly showed increasing

postoperative complication and mortality rates with

advanced age (42,89).

Decreased Life Spans in the Elderly--The progression from polyp to cancer and from early cancer

to late cancer is not well understood, but the process

is generally thought to be gradual, and does not

change with age. Studies of the growth rates of small

CRCs have indicated that colorectal tumors may

grow from 5 mm to 1 cm in a median time of 30 to 40

months, with a lower bound of 12 to 16 months (18).

Some experts claim that it takes from 5 to 10 years

for an adenomatous polyp of 1 cm in size to develop

into cancer (35,135). The slow progression of polyps

to cancer raises the question whether screening for

polyps in patients over 70 years of age can increase

longevity (135). Yet, avoiding CRC has benefits that

are independent of effects on length of life. The real

question is whether detecting and removing the

polyps and early cancers are worth the inconvenience, medical risk, and cost that are implied for the

very old.
Chapter 3

The Cost-Effectiveness of Colorectal Cancer Screening in the Elderly

INTRODUCTION

How cost-effective is colorectal cancer (CRC)

screening in the elderly? This question can be answered only by comparing the net health care costs

brought about by a screening strategy with the health

effects achieved as a result. The health effects of a

preventive strategy such as CRC screening include

impacts on quality of life as well as on its length.

Measuring these two dimensions of health effects is

often difficult; some cost-effectiveness analyses

include only mortality effects -- life-yeas gained --

and leave quality-of-life improvements implicit;

others attempt to capture both dimensions in composite measures such as “wellness years” or “qualityadjusted life years” gained from a preventive strategy.

Estimation of the cost-effectiveness of CRC

screening in the elderly is especially difficult because

of the uncertainty about whether CRC screening is

effective at all in preventing CRC or reducing its

lethality. If CRC screening is not effective in

reducing CRC incidence or mortality in the elderly,

then it is clearly not cost-effective. It is only costly.

It may even be both costly and risky, because the

screening and followup procedures brought about by

a screening strategy carry their own medical risks.

However, if CRC screening is effective in reducing

cancer incidence and death, then the ratio of net

health care costs to a measure of effectiveness can

help policy makers determine whether the strategy is

worth its costs and risks.

Whether CRC screening can extend the lives of

elderly people through prevention or earlier

detection of CRCs is not known at present. Indirect

evidence does exist, however, about the natural

course of the disease, the accuracy of the various

screening tests in detecting polyps and CRC, rates of

medical complications associated with the screening

tests, followup procedures and cancer treatment, and

the life expectancy of people with CRC at various

stages. Though this evidence is imperfect and has

some important gaps, if used judiciously it is possible

to explore the potential impact of CRC screening on

the health of elderly people. These potential net

health impacts can then be compared with the net

health care costs associated with screening in elderly

people.

To resolve the dilemma posed by uncertainty

about net effects, Office of Technology Assessment

(OTA) estimated the net health care cost per additional year of life gained from CRC screening using

data and assumptions that were in every case pessimistic toward screening. We examined the existing

evidence on screening test accuracy, the natural

course of the disease in the elderly, medical risks,

and costs with the objective of deliberately

underestimating the effectiveness and overestimating

the costs associated with screening. If the resulting

conservative estimate of cost-effectiveness of CRC

screening compares favorably with other preventive

interventions for the elderly, particularly those that

have already been included as Medicare benefits,

then confidence that CRC screening is at least as

cost-effective as these other services would be high.

The remainder of this chapter describes OTA’s

analysis of the cost-effectiveness of four alternative

strategies for CRC screening and compares the

results of that analysis with findings about other preventive services for the elderly and with other studies

of CRC cost-effectiveness.

SCREENING, FOLLOWUP, AND

SURVEILLANCE STRATEGIES

The National Cancer Institute (NCI) recommends that adults without specific risk factors for

CRC begin a program of periodic screening for CRC

at age 50 and continue for the rest of their lives. The

recommended screening program entails an annual

fecal occult blood test (FOBT) and flexible fiberoptic

sigmoidoscopy (FSIG) at 3- to 5-year intervals (See

table 2). OTA examined four screening schedules,

including the NCI schedules, for people beginning at

age 65 and continuing until they die or reach the age

of 85:

o Regimen 1: Annual FOBT and a sigmoidoscopic examination every 3 years;

-23-
24- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

o

0

0

Regimen 2: Annual FOBT and a sigmoidoscopic examination every 5 years;

Regimen 3: Annual FOBT and one sigmoidoscopic examination upon entry to Medicare at

age 65;

Regimen 4: Annual FOBT with no sigmoidoscopy.

For all regimens, screening was assumed to cease

when the individual reaches age 85, although surveillance of people previously found to have polyps

would continue for the rest of their lives. Because

the lengths of sigmoidoscopes vary, the model was

further refined to estimate separately the effectiveness and costs of screening with a 60 cm sigmoidoscope and a 35 cm sigmoidoscope. The longer

scope detects a greater proportion of colonic polyps

and cancers than the shorter one, but the costs and

medical risks of followup and surveillance are higher.

Over the course of their remaining lives, 65-yearold people would undergo repeated screening tests,

followup diagnostic testing when the screening tests

are positive, polyp removal (polypectomy) when

polyps are found as part of the screening or followup

tests, and periodic surveillance with colonoscopy

after polypectomy to screen for new polyps. In

addition, when cancers are found, patients undergo

evaluation and treatment for the cancer based on the

stage at detection.

The effectiveness and cost of following up on a

positive screening test depends on the diagnostic

technologies employed. Two alternative followup

protocols have been recommended (32,44,47,72,91,

122,143,155). The first is to go directly from a positive screening test to a full colonoscopy with

polypectomy if necessary. The alternative is to followup with sigmoidoscopy (if the screening test was

an FOBT) and a DCBE. The relative advantages of

the two followup procedures are currently subjects of

debate (44,53). Comparisons of relative accuracy,

procedure risk, patient comfort and cost underlie different conclusions about the two procedures.

In this study OTA assumed a positive screening

sigmoidoscop would result in full colonoscopy with

polypectomy. 1 All positive FOBT tests were also

assumed to result in a diagnostic colonoscopy and, if

a polyp is found, polypectomy. Pathological tests are

universally recommended for all removed polyps,

and the OTA analysis assumed that they will be

done.

Once a polyp has been discovered and removed,

the patient is typically subject to periodic surveillance

by colonoscopy, on the assumption that people previously discovered to have polyps are at higher risk of

future recurrence of polyps and cancers (87,114).

The American Gastroenterological Society recommends that surveillance begin one year after the

polypectomy and, if the first surveillance colonoscopy

is negative, that it continue at 3- to 5-year intervals

(44). A large multi-center randomized trial funded

by the NCI is currently underway to compare the

effectiveness of surveillance at 1 year and 3 years vs.

3 years after polypectomy (113). The OTA analysis

assumed a surveillance colonoscopy frequency of

every 4 years beginning 4 years after the initial

polypectomy, but the impact of moving to a 2-year

surveillance interval was investigated in a sensitivity

analysis reported later in this paper.

1The procedure costs of colonoscopy are higher than a combination of sigmoidoscopy and DCBE. The average Medicare

allowed payment for a sigmoidoscopy and a DCBE together in

1986 was $213 compared to $376 for a diagnostic colonoscopy and

$626 for a colonoscopy with polypectomy. The impact on total

costs of assuming followup with colonoscopy rather than with

FSIG and DCBE may not be to overestime costs, however. Any

polyps discovered by DCBE beyond the reach of the sigmoidoscope would be removed through colonoscopy, requiring an

additional procedure, and those within the reach of the followup

sigmoidoscopy might also require an additional procedure for

removal, thereby necessitating a further charge for the polypectomy. Because polyp are present in a high proportion of 65-

year-old people (perhaps as many as one-half), basing the cost of

diagnostic followup on the assumption that it will always be

colonoscopy does not substantially overestimate true costs. It

might even underestimate these costs in some circumstances. For

example, if 50 percent of all people referred for follow-up from a

positive FOBT had polyps, then the average followup cost of the

FSIG and DCBE in 1986 would have been $526 [1/2($213

+$626)+ 1/2($213)] compared to $445 [1/2($213)+ 1/2($676)] for

colonoscopy.
Chapter 3–The Cost-Effectiveness of Colorectal Cancer Screening in the Elderly- 25

STRUCTURE AND ASSUMPTIONS OF

THE COST-EFFECTIVENESS

ANALYSIS

The cost-effectiveness analysis enumerates and

estimates the size of the potential health effects and

health care costs of CRC screening over the

remaining lifetime of a cohort of 65-year-olds. The

analysis assumes that these people have not been

screened before reaching the age of 65 and that all

people in the cohort will fully comply with the

screening, followup and surveillance regimen. The

2.1 million people who were 65 years of age in 1989

served as the illustrative cohort for the analysis.

Table 5 arrays the potential effects and costs

brought about by any particular CRC screening

strategy. Notice that screening potentially affects

both costs and outcomes in both positive and negative ways. OTA’s analysis estimated the size of each

potential category of cost and effect except those

involving changes in quality of life. Individuals vary

greatly in perceptions of pain and discomfort associated with particular procedures. Consequently,

OTA did not attempt to adjust the analysis for

quality of life impacts but recognized that such considerations would and should enter into individual

clinical decisions about the value of CRC screening

in a particular person2

.

In OTA’s analysis a population of 65-year-olds

embarks on a screening regimen and begins to incur

costs and reap medical effects (measured by additions to or reductions in life expectancy) over the

succeeding years. The estimated costs and effects

incurred over time are discounted to their net

3 The size of these estimated costs and present value.

effects depends on assumptions about the following:

2These quality of life effects, particularly the discomfort of the

screening, followup and surveillance procedures themselves, may

partly explain why colorectal screening use rates are so low today.

%0 compare outlays occurring in different time periods, they

must each be discounted to their to their present value. The discounting of health effects as well as costs is necessary to insure

that programs whose benefits lie well in the future will not be

found more cost-effective if postponed indefinitely (77). A discount rate of 5 percent per year was used to convert both additional years of life gained (effects) and costs in future years to

their value in 1989.

Table 5- Effects and Coats of CRC Screening

in the Elderly

Effects

Longer life:

● Removal of polyps prevents cancers that would have been

fatal.

● Early detection of CRC reduces death rate from cancers.

Shorter life:

● Detection and removal of polyps carries small risk of colon

perforation and death.

● Surveillance with colonoscopy of people previously detected with polyps carries small risk of colon perforation and

death.

● Treatment of cancers detected in screening that would have

remained latent for the duration of the patient’s life carries

risk of surgical, medical complications.

Higher quality of life:

● pain associated with cancer or cancer treatment is avoided

for those whose cancer would have been clinically detected

in the absense of screening.

Lower quality of life:

● Discomfort, pain is incurred from screening, followup, and

surveillance procedures.

● Pain of cancer treatment is incurred for those whose cancer

would have remained latent for the rest of their lives.

● False positive screening results cause unnecessaryanxiety.

costs

Higher costs:

● Screening and followup tests cost money.

● Polyp removal procedures cost money.

● Surveillance procedures for those found with polyps cost

money.

● Treatment of cancers that would have remained latent for the

duration of the patient’s life costs money.

Lower costs:

● Reduction in need for cancer treatment due to prevention of

CRC saves COStS.

● cost of cancer treatment is reduced due to detection in earlier stages where treatment is less expensive.

SOURCE: Office of Technology Assessment, 1990.

0 natural history of the disease:

the underlying prevalence of polyps and

cancers by stage in 65-year-olds;

the incidence of new polyps and cancers at

various stages that would be expected in

succeeding years in the absence of

screening;

the rate at which polyps become cancers

and early cancers progress to late cancers;

the rate at which latent cancers become

diagnosed clinically;

the life expectancy of people in each year

from age 65 to 85 without CRC and with

CRC detected in early and late stages;
26- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

o test accuracy:

the sensitivity and specificity of the

screening, followup and surveillance tests

in detecting polyps and CRC;

o medical risks:

the rates of colon perforation and death

from screening, followup and surveillance;

the rate of surgery-related mortality associated with treatment of cancer;

0 costs:

the costs of screening, followup, polyp

removal, surveillance, and treatment of

early and late cancers;

the cost of treating colonoscopy-induced

injuries;

the cost of treating surgery-related injuries

in patients with cancers that would have

remained latent in the absence of

screening for the remainder of the

patient’s life (“lifetime latent” cancers).

Detailed descriptions of the sources of data and

rationale for assumptions in each of these areas are

presented in appendix C. Table 6 summarizes the

critical assumptions underlying the results presented

for the pessimistic analysis.

RESULTS

Table 7 shows the results of a cost-effectiveness

analysis of the four screening regimens under

assumptions that are pessimistic about the costeffectiveness of CRC screening. Regardless of the

screening regimen employed, CRC screening is

potentially costly. The present value of the net

lifetime health care costs of periodically screening

the 1989 population of 65-year-olds could be as high

as $1.5 billion to $2.6 billion if all of these people

were to fully comply with the screening, followup and

surveillance protocols. This net lifetime expenditure

amounts to about $737-$1,263 for every person who

does comply with the protocols.

The net costs of screening regimens that involve

FSIG are much higher than the net cost of an annual

FOBT, largely because FSIG is such a sensitive

Table 6-Summary of Assumptions for CoatEffectiveness Analysis

Accuracy

FOBT sensitivity for polyps . . . . . . . . . . . . . . . . . . . . . 10%

FOBT sensitivity for CRC . . . . . . . . . . . . . . . . . . . . . . . 40%

FOBT specificty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96%

FSIG sensitivity for polyps

– for polyps destined to become

clinically detected cancer. . . . . . . . . . . . . . . . . 92%

– for polyps destined not to

progress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96%

FSIG sensitivity for CRC . . . . . . . . . . . . . . . . . . . . . . . 92%

Reach of 60 cm FSIG

– for polyps destined to become

clinically detected cancer. . . . . . . . . . . . . . . . . 35%

– for polyps destined not to

progress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70%

– for CRC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35%

FSIG Specificity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95%

Natural history of the disease

Percent of all clinically detected

cancers that begin as polyps . . . . . . . . . . . . . . . . 57%

Number of years for a 5 mm adenoma

to progress to CRC . . . . . . . . . . . . . . . . . . . . . . . . 6

Number of years required for a new

invasive CRC to progress to late

CRC (for CRCs destined to be

clinically detected) . . . . . . . . . . . . . . . . . . . . . . . . . 1

Number of years required for a late

CRC destined to be clinically

detected to be detected . . . . . . . . . . . . . . . . . . . . 1

Percent of CRCs clinically detected

in early stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40%

Prevalence of lifetime latent cancers

at age 65 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5/1000

Annual incidence of lifetime latent

cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5/10,000

Medical risks

Rate of colonoscopy-induced

perforation of the large bowel . . . . . . . . . . . . . . . . 0.1%

Colonoscopy-induced motility rate . . . . . . . . . . . . . . 0.02%

Surgery related mortality in patients

with primary colorectal cancer

surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7%

coats

Cost of FOBT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $3.56

Cost of Screening FSIG . . . . . . . . . . . . . . . . . . . . . . . . $96

Cost of diagnostic colonoscopy . . . . . . . . . . . . . . . . . $411

Cost of colonoscopy with . . . . . . . . . . . . . . . . . . . . . . $653

polpectomy

cost of pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . $51.37

Cost of treating early cancer . . . . . . . . . . . . . . . . . . . . $20,000

Cost of treating late cancer . . . . . . . . . . . . . . . . . . . . . $30,000

Cost of treating colonoscopy-induced . . . . . . . . . . . . $20,000

perforations

Cost of treating colonoscopy-induced . . . . . . . . . . . . $30,000

deaths

Cost of treating fatal complications

in early cancer patients . . . . . . . . . . . . . . . . . . . . . $30,000

SOURCE: Office of Technology Assessment, 1990.
Table 7-Cost-Effectiveness of Colorectal Cancer Screening in the 1989 U.S. 65-Year-Old Population Under Assumptions Unfavorable

to Screeninga,b

Cost

costs Effects Effectiveness

Years of

life Years

Extra costs gained Years of life

Costs of of treating Net from of life lost from Cost per

screening, lifetime Savings in additional Number of reduction lost from complications Net gain year

followup and latent treatment costs of cancers in cancer operative of in years of life

screening Regimen surveillancec,d cancersc,f costsc,d screening prevented mortalityc mortality colonosoopyc of Iifec gainedc,e

Regimen 4:

Annual FOBT $1.597 billion

Regimen 3:

Annual FOBT

60cm FSIG on entry

to Medicare $2.526 billion

Regimen 2:

Annual FOBT

60cm FSIG

every 5 yrs $2.705 billion

Regimen 1:

Annual FOBT

60cm FSIG

every 3 Yrs . . $2.849 billion

$0.387 billion

$0.397 billion

$0.404 billion

$0.404 billion

$0.450 billion $1.534 billion

$0.524 billion $2.399 billion

$0.604 billion $2.504 billion

$0.623 billion $2.630 billion

22,756 61,821 12,723 5,340 43,758 $35,054

26,484 72,455 13,316 8,425 50,714 $47,308

32,579 81,016 13,567 8,528 58,92’ $42,509

33,549 83,593 13,660 8,610 61,323 $42,892

FOOTNOTES:

aFor assumptions, ~t- 6.

b~s sh~n in tile Me rounded to the nearest million doliars Underlying calculations cSarriOd OUt Ofl em Illimhre

Cyeam ~ l~e ad costs we discount~ to pr~nt v~ue @ a r~e of 5 percent per year.

dThis ~WoV incjud~ costs of treating complications of colon~py

e~m~ed to no screening.

fThis ~t~o~ inclwes coats of treatin9 complications of surgery.

SOURCE: Office of Technology Aeeessment, 1990.
28- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

detector of polyps. Once an adenomatous polyp is

detected and removed, a person enters a costly

schedule of surveillance by colonoscopy.4

Table 8-impact of Surveillance Schedule on the

Cost-Effectiveness of CRC Screening in the 1989

U.S. 65-year-old Populationa

The screening procedures alone (FOBT and

FSIG) represent a relatively small proportion of the

overall cost of the program. For example, screening

costs constitute 4 percent of the total costs of

screening, followup and surveillance under Regimen

4 (which has no sigmoidoscopy) and 18 percent of

the total screening, followup and surveillance costs of

Regimen 1, the most intensive screening schedule.

Followup and surveillance costs are each a large part

of lifetime costs, because 45 percent of the population sooner or later will be subjected to followup

and then surveillance under Regimen 4 (FOBT only)

and 55 percent would ultimately be placed in surveillance under any screening regimen involving FSIG.

The importance of surveillance as a component of

program costs suggests that costs to Medicare are

likely to be high even if screening begins well before

the person becomes eligible for Medicare. For

example, if all people begin CRC screening in

keeping with the NCI guidelines at 50 years of age,

then many of those with colorectal polyps would

already be in a surveillance pool at the time they

reach age 65. Though they would not be incurring

additional screening and followup costs, they would

be in surveillance from the time of entry into

Medicare through the rest of their lives.

The net costs of the program could be even

higher than those presented here if the schedule of

surveillance by colonoscopy were reduced from four

years to two. In that case, the total cost associated

with screening increases to between $2.3 billion and

$3.9 billion, depending on the screening regimen

employed (table 8).

4The screening, followup, and surveillance costs shown in Table 7

assume that FSIG screening will be performed with a long (60

cm) FSIG. Use of the shorter (35 cm) FSIG would lower the

screening, followup and surveillance costs but would also reduce

the effectiveness of screening.

Surveillance schedule

Cost per year

Total program costs of life gained b

4 year 2 year 4 year 2 year

Regimen 4C. . . . . . $1.534

billion

Regimen 3d. . . . . . $2.399

billion

Regimen 2e. . . . . . $2.504

billion

Regimen 1’. . . . . . $2.830

billion

$2.320 $35,054 $58,879

billion

$3.785 $42,509 $70,140

billion

$3.893 $42,892 $69,445

billion

ABBREVIATION: FOBT = fecal occult blood test.

aScreening with a 60 cm sigmoidoacope.

b~st Md years of life gained in the future are discounted to their present value@ a

rate of 5 percent per year.

cRWimen 4: Annu~ FOBT; sigmoidoseopy evefy 3 ~.

d R~imen 3: Annual FOBT; sigmoidoscopy every 5 YE@’$.

eRegimen 2: Annual FOBT; sigmoidoscopy once upon entry to Medic.Ms.

fRWimen I: Annu~ FOBT; no sigmoidoscopy.

SOURCE: Office of Technology Assessment, 199Cr.

The analysis suggests that in preventing some

cancers (between 22,000 and 33,000 depending on

the screening regimen) and detecting others in an

earlier stage than they would otherwise be detected,

substantial savings in health care costs are obtained,

but these savings are markedly reduced by the extra

costs of treating the many lifetime latent cancers

detected through screening. With Regimen 4 (FOBT

only) the net saving in cancer treatment cost is only

$63 million, a small sum compared to the $1.6 billion

spent in screening, followup and surveillance (table

7).

The potential health benefits achieved by this

high cost are substantial. Under the assumptions of

the OTA analysis, annual FOBT screening would

prevent almost 23,000 cases of CRC that are

otherwise destined to become clinically manifest

sometime during the remainder of the population’s

life. This represents approximately 17 percent of all

cancer incidence expected in the 65-year-old population. In addition to this gain, some cancers that

would have manifested themselves in late stages will,

under screening, be detected in early stage, with con-
Chapter 3--The Cost-Effectiveness of Colorectal Cancer Screening in the Elderly-29

sequent improvements in survival. Taken together,

the benefits of prevention and early detection of

CRC result in a total gain of between 43,000 and

61,000 additional years of life5 in the cohort under

study (table 7).

The critical measure of cost-effectiveness is the

cost per added year of life from a specific CRC

screening regimen. As table 7 shows, adopting a

CRC screening program for the elderly costs

between $35,000 and $47,000 per added year of life

gained, depending on the particular screening

regimen adopted. Strategy 4 (FOBT only) is the most

cost-effective strategy compared to no screening.

The cost-effectiveness of CRC screening depends

strongly on the surveillance protocol adopted. The

high procedure cost of colonoscopy relative to the

screening procedures makes colonoscopy a critical

resource whose overuse could render CRC screening

much more expensive per year of life gained. As

table 8 shows, a 2-year surveillance schedule

increases the total costs of the program by almost 50

percent and raises the cost per year of life saved by

over 60 percent, to about $57,000 in the case of

Regimen 4. In keeping with the pessimistic structure

of the analysis, OTA assumed that surveillance

colonoscopy adds no health care benefits beyond

those achieved by the discovery and removal of the

initial polyp in screening. Consequently, the extra

costs and risks of more frequent surveillance add

only costs and reduce effectiveness without providing

any compensating benefits. The National Polyp

Study currently underway is intended to determine

whether more frequent surveillance does improve

outcomes; in the meantime, it is worth noting that

the total costs of any CRC screening program are

very sensitive to the surveillance schedule.

The cost per year of life saved for each of the

screening regimens is based on a comparison with no

screening. Ideally, decisions about the frequency of

screening with FSIG should be made by comparing

the incremental, or additional, costs with the additional health benefits of moving from no FSIG

screening or from a less frequent screening interval

to the next most frequent screening interval. After

5Years of life gained in future years are discounted to their

present value at a rate of 5 percent per year.

all, more frequent screening costs more money. That

extra cost should be compared with the extra benefits

it provides. Unfortunately, the model is not a

reliable estimator of these incremental costs and

effects. OTA assumed that cancers destined to be

diagnosed clinically (in the absence of screening)

progress very rapidly. While this assumption

underestimates the effectiveness of any screening

regimen compared to no screening, it also overestimates the effectiveness of more intensive or frequent screening compared to less intensive screening

regimens. If CRCs destined to be diagnosed clinically progress slowly, then infrequent screening with

FSIG should be almost as effective as, and much less

costly than, more frequent screening with FSIG.6

The pessimistic assumptions regarding the speed of

polyp and cancer progression (i.e., very fast progression from early to late cancer for those cancers

that would become clinically manifest without

screening) makes more frequent screening with sigmoidoscopy appear incrementally more effective

than it would be if cancers actually progress more

slowly.

Because the model is deliberately biased upward

in cost and downward in effectiveness when comparing each regimen with no screening, OTA is reasonably confident that, compared to no screening at

all, screening according to one of the four schedules

provides an added year of life at a cost no greater

than, and probably less than, those shown in Table 7.

Studies of other preventive services legislated as

covered services under Medicare in the past

(pneumococcal pneumonia vaccine, cervical cancer

screening, and breast cancer screening) have

reported lower costs for each additional year of life

gained from screening. (36,149,150) However, when

both costs and years of life gained were discounted to

their present value at an annual rate of 5 percent, as

they are in this study, breast cancer screening with

mammography was estimated to cost about $34,000

per year of life gained. This is approximately equal

to the cost per year of life gained from annual FOBT

screening in the elderly under the pessimistic set of

assumptions.

%0 test this assumption, OTA lengthened the assumed CRC

progression rate from one year to three years. As expected, the

cost per year of life gained compared to no screening declined,

but the additional cost per additional year of life gained from

offering more frequent FSIG screening compared to less frequent

FSIG screening increased greatly.
30- Costs and Electiveness of Colorectal Cancer Screening in the Elderly

To summarize the results of this analysis, under

pessimistic assumptions about the potential effectiveness and costs of screening, the discounted cost

per year of life gained for FOBT is within the range

of cost-effectiveness values calculated for mammography screening in elderly women (36), provided

that the post-polypectomy surveillance schedule is

no more frequent than every 4 years. Thus, if the

assumptions outlined above are as conservative as we

believe them to be, CRC screening is as costeffective as one other preventive intervention that

had been covered under Medicare. 7 At the same

time, it is impossible to say whether the extra costs of

periodic sigmoidoscopy compared to annual FOBT

alone are high or low in relation to the extra medical

benefits they provide, because the magnitude of

those incremental costs varies so greatly with

changes in assumptions about the rates of polyp and

cancer progression. Indeed, if the great majority of

polyps and cancers progress much more slowly than

assumed in the model, the incremental cost of

regimens 1 to 3 (i.e., those involving FSIG) relative

to regimen 4 (FOBT only) would be very high. Yet,

the cost per year of life saved compared to no

screening for any of the screening regimens would be

even lower than they are in table 7.

Distribution of Effects Across Time and

Individuals

The estimated cost per year of life gained

represents an average of medical gains and losses

incurred by different people at different times in

their lives. CRC screening subjects some people to

risks of illness and death that they would not have

suffered had they not been screened. Those risks are

borne relatively early in their remaining lives,

whereas the substantial gains from reductions in the

incidence and lethality of cancer occur later on. For

example, under the pessimistic assumptions, an

annual FOBT would detect about 4,200 lifetime

latent cancers in year 1, when the 2.1 million 65-

year-olds have just enrolled in Medicare; an

estimated 300 of these people would die in that year

7Mammography was briefly legislated as a covered benefit under

Medicare, but because it was legislated as part of the Medicare

Catastrophic Health Act of 1988, the provision was repealed

when the Catastrophic law was repealed late in 1989.

from complications of surgery for CRC. These 300

excess deaths in the first year of screening must be

weighed against the 23,000 eases of cancer prevented

and the lives saved from early detection of the

cancers that are not prevented, both of which occur

later in life. To some extent, discounting lives saved

in future years to their “present value” takes account

of these differences in the time distribution of effects.

Yet, the selection of a uniform discount rate for all

people, necessary for a public policy analysis, masks

wide variation in individuals’ preferences for early

losses versus late gains in life expectancy. Differing

valuations of the tradeoff between risks now and

risks later on could make an individual’s assessment

of the cost-effectiveness of CRC screening very different from the estimates given in this paper.

Sensitivity Analysis

OTA attempted to submit CRC screening to a

stringent test of cost-effectiveness by making

assumptions that were uniformly unfavorable to

screening. For most of the assumptions, we are reasonably confident that the true value is more

favorable to screening than the value assumed in the

analysis. By combining so many unfavorable

assumptions together, the analysis represents a reasonable upper bound on the potential costs per year

of life gained from each screening regimen.

Data were very sparse to support several assumptions (Appendix C). The most uncertain and potentially important are the costs of treating early and

late cancer; the speed of progression of polyps to

cancer; and the sensitivity of FOBT for early cancer.

Although OTA attempted to be conservative about

each of these assumptions, it is important to know

how the results of the cost-effectiveness analysis

would change if the true values were at levels even

more unfavorable to screening than those assumed in

the original analysis.

Costs of Cancer Treatment

The cost-effectiveness model assumed that the

additional net costs of treating early and late cancer

are $20,000 and $30,000 respectively. The basis for

these estimates is tenuous. Higher costs lead to

greater savings in the cost of treating cancers that are

prevented or detected earlier than they would be
Chapter 3–The Cost-Effectiveness of Colorectal Cancer Screening in the Elderly- 31

without screening but they also increase the costs of

treating lifetime latent cancers detected through

screening. Consequently, the impact of any change

in cancer treatment costs cannot be predicted

beforehand. OTA examined how reductions in the

cost of early and late cancer treatment would affect

the outcome of the analysis.

Table 9 shows the results of changing these values

on the estimated cost-effectiveness of regimens 4 and

2. As the table shows, the costs of cancer treatment

have little effect on the cost per year of life gained

from screening. Even under the extreme assumption

that the discounted cost of treating both early and

late cancers is only $5,000, the net discounted cost

per year of life gained from screening rises from

about $35,000 to $37,000 for FOBT.

Speed of Polyp/Cancer Progression

Although most experts believe that the polyp/

cancer sequence occurs over a long period of time, it

is possible that the most lethal cancers -- those

destined to be discovered late and to be least

responsive to therapy --progress more quickly, even

when they are still polyps. Changing the assumptions

about the speed with which polyps that are destined

to become clinically detected cancers actually

progress from their beginning to early stage cancer

has a greater impact on estimated cost-effectiveness

than do changes in the cost of cancer treatment. If

the polyp/cancer progression time is assumed to be 3

years in length rather than 6 years, the cost per year

of life gained from an annual FOBT screen increases

Table 9-Cost-Effectiveness of CRC Screening

Under Differing Assumptions About the Cost of

Treating Early and Late CRCa

Cost per Cost per

added added

cost of cost of year of year of

treating treating life life

early CRC late CRC Regimen 4b Regimen 2c

$5,000 $5,000 $37,150 $45,950

$5,000 $10,000 $35,120 $44,171

$10,000 $15,000 $35,774 $44,210

$10,000 $20,000 $33,745 $42,430

$20,000 $30,000 $35,054 $42,509

atist9 and ~of life discounted at annual rate of 5 percent.

b Regimen 4 = annual FOBT.

C RWimen 2. annu~ FOBT + FSIG *V 5 ~

SOURCE: office of Technology Assessment, 1990.

Table 10- Sensitivity of Coat-Effectiveness Results

to Faster Polyp/Cancer Progression Timea

Cost per year of Cost per year of

life gained life gained

Screening with 6 year with 3 year

regimen progression time progression time

4 $35,054 $50,992

3 $47,306 $71,547

2 $42,509 $59,751

1 $42,692 $51,666

a ~NPiCmmr ~W~ion time refers to the number of years fora P@pthat is destined to be detected without screening to progmsfrom it’searliest detectable state

to invasive cancer.

SOURCE: Office of Technology Assessment, 1990.

to almost $51,000 (table 10). Other screening

regimens also become substantially more expensive

for the medical benefits they produce.

FOBT Sensitivity for Early Cancer

OTA assumed that FOBT can detect a cancer

(early or late) with a 40 percent probability. (See

app. C for the evidence on which this assumption is

based.) This is substantially lower than the values

used in recent cost-effectiveness studies of FOBT

screening (8,39). Although this assumption is on the

low end of the existing studies of FOBT sensitivity,

most studies of FOBT sensitivity include symptomatic patients, who would be more likely to

present with blood in the stool. One study comparing FOBT with sigmoidoscopy in asymptomatic

non-elderly people found a sensitivity for cancer of

25 percent (6). OTA examined the impact on costs

and effectiveness of using this lower value. As table

11 shows, changing this assumption raises the cost

per additional year of life gained by about 23 percent,

to $43,000 for screening regimen 4 (FOBT only) but

has less proportional impact on regimens that

include FSIG.

Table 11- Effect of Lower FOBT Sensitivity on CostEffectiveness of CRC Screening

Cost per year of life

gained from screening

Screening FOBT sensitivity FOBT sensitivity

regimen 25%

4 $35,054 $43,167

3 $47,306 $55,525

2 $42,509 $48,338

1 $42,692 $46,194

SOURCE: Office of Technology Assessment, 1990.
32- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

Comparison With Other CRC CostEffectiveness Analyses

Several researchers have analyzed the costeffectiveness of CRC screening, but none has

examined the effectiveness and cost of repeated

screens beginning at 65 years of age. Barry, Mulley

and Richter (8) examined the cost-effectiveness of a

one-time FOBT screen for an asymptomatic 65-yearold who had not been previously screened. The gain

in years of life from screening was based on assumed

changes in the stage distribution of cancers detected

as a result of the screening examination. They found

that the net discounted cost8 per added year of life

ranges from about $9,000 to $14,000, depending on

the followup procedures used. Their analysis

assumed that the prevalence of polyps in this population would be about 18 percent, a substantially

lower estimate than OTA used. The low estimate of

polyp prevalence reduces the estimated costs of following up positive FOBT examinations. Barry and

Mulley also did not include the costs of surveillance

following polypectomy, which represent a major

component of net health care costs in the OTA

study.

England and colleagues (40) studied the effect of

a one-time colorectal screening examination in a

population of asymptomatic people 40 years and

over. The impact of screening on life expectancy was

based on assumptions about the shift in the stage distribution of cancers that can be expected from

screening. The analysis did not include the costs of

surveillance resulting from detection and removal of

polyps, and it did not estimate the savings in health

care costs that can be expected from improvements

in the stage at detection. The authors found that the

cost per year of life gained9 from an FOBT and sigmoidoscopic examination ranged from $19,000 to

$21,000.

Allison and Feldman examined a one-time FOBT

screen in people 45 years of age and older who were

enrolled in an Health Maintenance Organization

(HMO) in 1979-1980 (l). The gains in survival from

screening were estimated by comparing the stage dis8The discount rate was 6 percent in that study.

9

Neither costs nor years of life were discounted in this analysis.

tribution of CRCs detected in the HMO in 1974

(before screening was available) with that observed

in the screened patients in 1979-1980. Savings in

medical care costs were netted out of the total cost

estimate, but surveillance costs were not included in

the analysis. The FOBT was found to cost $765 per

person-year of extended life.10

In several studies based on a mathematical model

of CRC, Eddy and colleagues (33,35,39) estimated

the cost-effectiveness of alternative screening and

followup strategies for various populations. The

impact of screening at various frequencies with different combinations of potential screening tests was

calculated based on assumptions about the natural

history of polyps and cancer that are similar but not

identical to those used by OTA. Costs include

screening and followup but not surveillance. Nor did

the analyses account for the cost or risk of treating

screening-detected cancers that would otherwise

remain latent through the remaining life of the

screened individual. The net savings in the costs of

treating CRC were subtracted from total costs.11 In

the most recent version of the model, Eddy assumed

a lower sensitivity of FOBT for polyps than did OTA.

Eddy assumed an effective sensitivity for polyps of 19

percent for just the last 2 years before the polyp

progresses to invasive cancer. While most of Eddy’s

other assumptions are more favorable to screening

than are OTA’s assumptions, this assumption significantly reduces the potential effectiveness of

FOBT to prevent cancer compared to OTA.12 In

average risk 50-year-old men, the net discounted cost

per additional year of life gained from a screening

regimen that would continue to age 75 was estimated

at about $19,200 for an annual FOBT and sigmoidoscopy every 5 years, and $25,300 for an annual

FOBT and a sigmoidoscopy every 3 years (39).

10 Costs and years of life gained were not discounted in this

analysis.

11Both costs and increases in life expectancy were discounted at 5

percent.

12For example, in OTA’s analysis, a cancer that would become

clinically manifest in its late stage at age 75 has six chances to be

detected (between the ages of 67 and 72), with a 10 percent

probability of detection in each year. This corresponds to an

overall probability of detection as a polyp of 47 percent, compared to an overall detection probability in Eddy’s study of 36

percent.
Chapter i3--Xhe Cost-Effectiveness of Colorectal Cancer Screening in the Elderly- 33

Discussion

Virtually all cost-effectiveness analyses of CRC

screening, including our own, have concluded that

this kind of cancer screening delivers substantial

benefits with a sizable investment. All of the models,

including our own, assume that it is possible to

prevent cancer or alter the pattern of mortality from

the disease through early detection. Definitive evidence that screening can indeed deliver such effects

simply does not exist. Yet, in building from what is

known about the polyp and cancer detection capability of the screening tests and the natural course of

the disease, we concluded that CRC screening is

likely to deliver health benefits at a cost that is

roughly in line with those offered by at least one

other preventive health service that was covered

under Medicare.

The uncertainty about the relative merits of

alternative CRC screening strategies is great,

however, and the potential costs of screening, followup and surveillance are high. In particular, the

incremental cost of each year of life added by sigmoidoscopic screening (on top of an annual FOBT)

is unclear and could well be very high. The sigmoidoscopy screening clinical trial currently under

development at the National Cancer Institute

promises to provide information on the medical

effects and net health care costs of sigmoidoscopic

screening in older Americans within 10 to 15 years

(152).

IMPLICATIONS FOR MEDICARE

OTA’s cost-effectiveness analysis followed a

cohort of 65-year-olds through the remainder of their

lives. The net program costs represent the discounted value of the stream of outlays over the next

30 or more years for people who were 65 years old in

1989. If Medicare were to offer a CRC screening

benefit, all elderly people, not just those newly

eligible for Medicare in years after coverage begins,

would be offered screening. What is the magnitude

of the health care costs that would be incurred in any

year?

OTA calculated the annual national costs associated with screening, followup and surveillance of

three CRC screening regimens beginning in 1989

assuming that all elderly people fully comply with the

screening, followup and surveillance protocols. (The

savings in health care costs from reductions in cancer

treatment and the added costs of treating lifetime

latent cancers were not included, but as table 7

showed, these other components of cost are

minuscule compared to the costs of screening, followup and surveillance.) For this estimate of the

annual national health care bill associated with CRC

screening in the elderly, OTA made more realistic

(i.e., less pessimistic) about the accuracy of the

screening tests and the prevalence and incidence of

polyps in the population (table 12).

Costs vary from year to year as the program gears

up and the size and age-distribution of the population over 65 years of age changes. In the ninth year

of program operation, the annual cost of Regimen 1

with 60 cm FSIG (in 1988 dollars) would be $2.5

billion, and the cost of Regimen 2 would be $2.2

billion. Regimen 4 (FOBT only) would be substantially less expensive to implement ($1.2 billion per

year) because it excludes the costs of FSIG and all

the followup and surveillance that would have been

induced by detection of polyps at sigmoidoscopy.

Chart 2 shows the estimated annual cost for each of

the three screening regimens during the first nine

years of operation of such a program.

If CRC screening were a covered Medicare

benefit, Medicare’s share of the net cost would be

high. Even today, Medicare covers a large but

unknown proportion of such costs because all diagnostic, followup, and surveillance procedures are

Table 12-Assumptions Underlying Estimates of the

Annual National Costs of CRC Screening, Followup,

and Surveillance In the Elderly

FOBT sensitivity for polyps . . . . . . . . . . . . . . . . . . . . . . . . 5%

FOBT specificity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98%

FSIG sensitivity for polyps . . . . . . . . . . . . . . . . . . . . . . . . . 95%

FSIG specificity . . . . . . . . . . . . . . . . . . . . . ............10096

Reach of 60cm FSIGa . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50%

Reach of 35cm FSIGa . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30%

Prevalence of polypsb . . . . . . . . . . . . . . . . . . . . . .......5096

aPercent of polyp located within the reach of a FSIG of designated length.

bpe~nt of S!j-year-olds with colonic POIYFS.

SOURCE: Office of Technology Aeaesement, 19S0.
34- Costs and Electiveness of Colorectal Cancer Screening in the Elderly

Chart 2--Annual Cost of CRC Screening, Followup, and Surveillance

($ billions)

(a) all regimens include FOBT annually

SOURCE: Office of Technology Assessment, 1990.

covered Medicare services. The cost of screening

alone is just the tip of the iceberg. Medicare allowed

under $4 for an FOBT and about $100 for FSIG in

1988 (if performed for diagnostic, not screening purposes).

The annual cost profile outlined in chart 2

represents the net additional cost of screening, followup and surveillance compared to no such procedures in the population. However, a small but

growing number of elderly people already receives

CRC screening, and Medicare is already paying for

the diagnostic followup and surveillance procedures

engendered by the screening examinations.2

2Medicare may be paying inadvertently for some screening procedures if they are billed as diagnostic procedures. Evidence has

accumulated that full colonoscopy used as a screening procedure

may be paid for by Medicare in a substantial number of cases

(98,151).

The national cost estimates assume that all

elderly Medicare beneficiaries will fully comply with

the screening regimen and all followup and surveillance procedures resulting from screening. In reality,

the use of CRC screening examinations in the elderly

is quite low, and it is unknown how much it will

increase by making a combination of FOBT and

FSIG a covered Medicare benefit. In 1987, for

example, only 34 percent of people 60 years of age or

over reported ever having undergone a screening

FOBT test and 7.4 percent reported ever being

screened with proctoscopy (rigid sigmoidoscopy)

(152). Whether paying $4 for a FOBT will bring

forth substantial additional use is unknown. The

actual impact of an FOBT benefit on annual health

care costs will depend on the degree to which

covering the service will encourage use. Also, if a

screening benefit brings about greater increases in

use of those at lowest risk of CRC, then the medical

benefits projected in the cost-effectiveness analysis

would be reduced, and the cost per added year of life

would be higher.
Appendix A

Advisory Panel--Project on Preventive Health Services Under Medicare

Gordon De Friese, Panel Chair

Health Services Research Center

University of North Carolina, Chapel Hill, NC

Marianne C. Fahs

Department of Health Economics

Mt. Sinai Medical Center

New York, NY

John Frank

Department of Preventive Medicine & Biostatistics

University of Toronto

Ontario, Canada

Gary D. Fredman

Epidemiology and Biostatistics Division

Premenente Medical Group, Inc.

Oakland, CA

Lawerence Gottlieb

Clinical Guidelines Programs

Harvard Community Health Plan

Brookline Village, MA

Mary Knapp

John Whitman and Associates

Philadelphia, PA

Risa Lavizzo-Mourey

Geriatrics Program

University of Pennsylvania

Philadelphia, PA

M. Cristina Leske

Department of Preventive Medicine

SUNY at Stony Brook

Stony Brook, NY

Donald Logsdon

INSURE Project

New York, NY

Mildred B. McCauley

American Association of Retired Persons

Washington, DC

Peter McMenamin

Chevy Chase, MD

Meredith Minkler

Center on Aging

University of California, Berkeley

Berkeley, CA

Marilyn Moon

The Urban Institute

Washington, DC

George Morley

Department of Obstetrics/Gynecology

University of Michigan Medical Center

Ann Arbor, MI

Gilbert Omenn

Dean, School of Public Health & Community Medicine

University of Washington

Seattle, WA

George Pickett

Department of Public Health Policy

School of Public Health

University of Michigan

Ann Arbor, MI

Donald Shepard

Department of Health Policy and Management

Harvard School of Public Health

Boston, MA

Barry Stults

Division of General Internal Medicine

University of Utah Medical Center

Salt Lake City, UT

NOTE: Advisory Panel members provide valuable guidance during the preparation of OTA reports. However, the

presence of an individual on the Advisory Panel does not mean that individual agrees with or endorses the

conclusions of this particular report.

-35-
Appendix B

Acknowledgments

This background paper has benefited from the advice of many people in addition to the advisory panel. The

staff would like to express its appreciation to the following people for their valuable help and guidance.

Renaldo N. Battista Robert S. Lawrence

Montreal General Hospital The Cambridge Hospital

Montreal, Quebec Cambridge, MA

John Bond Jack S. Mandel

Veterans Administration Medical Center University of Minnesota

Minneapolis, MN Minneapolis, MN

Martin Brown William Mayers

National Institutes of Health Wyatt Co.

Bethesda, MD Washington, DC

Morris F. Cohen Anthony B. Miller

Kaiser-Permanante Medical Care Program University of Toronto

Oakland, CA Toronto, Ontario

David M. Eddy

Jackson, WY

Jonathan Fielding.

U.C.L.A.

Los Angeles, CA

Alan Garber

National Bureau of Economic Research

Stanford, CA

David A. Gilbert

Seattle, WA

Pearl S. German

Johns Hopkins University

Baltimore, MD

Peter Greenwald

National Cancer Institute

Bethesda, MD

Robert Kane

University of Minnesota

Minneapolis, MN

Kevin Knight

Santa Monica, CA

Philip Prorock

National Cancer Institute

Bethesda, MD

David Ransohoff

Yale University

New Haven, CT

Charles R. Smart

National Cancer Institute

Bethesda, MD

Katharine Bauer Sommers

Institute of Medicine

Washington, DC

Linda Johnson White

American College of Physicians

Philadelphia, PA

T. Franklin Williams

National Institute on Aging

Bethesda, MD

Sindey Winawer

Memorial Sloan Kettering

New York, NY

-36-
Appendix C

Basis for Cost-Effectiveness Analysis of Colorectal Cancer Screening

MEASUREMENT OF EFFECTS

Natural History of Colorectal Cancer (CRC)

The Office of Technology Assessment (OTA)

cost-effectiveness analysis traces the experience of a

population of 65-year-old people through the

remainder of their lives, recording from year to year

the incidence of newly detected cancers by stage in

an environment first without any CRC screening and

then under each of the four CRC screening regimens. The difference between the screening and

no-screening scenarios in incidence by stage of

detected cancers is then combined with stage-specific

CRC mortality data to estimate the net gains in

expected years of life for the population from prevention and early detection.

The incidence of clinically detected CRC in the

absence of screening can be estimated from The

National Cancer Institute’s (NCI) Surveillance,

Epidemiology and End Result (SEER) tumor

registry data for the period 1979-1984 (152).

Although the observed incidence in these years

reflects a certain number of cases detected through

screening and therefore may be skewed toward

detection of cancers earlier in the lives of elderly

people than would occur without any screening, the

actual use of CRC screening by the elderly in the

early 1980s was quite low, so the bias toward early

detection in this group is likely to be small. The distribution of stages of clinically detected cancers (i.e.,

in the absence of screening) was also estimated from

SEER data. National data on the stage at detection

are unavailable for specific age groups, but numerous

studies have shown that the stage distribution of

clinically detected CRCsS does not vary appreciably

with age except for very young people (58,73,75,104).

Between 35 and 40 percent of all CRCs are detected

in early (localized) stages (152). A higher estimate

will be less favorable to screening, so OTA assumed

1

For example, in 1980, only 28 percent of all people 60 years of

age or older had ever had an FOBT for any reason (screening or

symptoms) and only 31 had had a rigid sigmoidoseopic examination (52).

that in the absence of a screening program the percentage of clinically detected cancers that would be

found in early stages was 40 percent.

To estimate how the incidence of clinically

detected CRC will change under a given CRC

screening regimen, one must know the prevalence of

polyps and silent cancers (both early and late) in the

population at age 65, the incidence of new polyps and

silent cancers in each succeeding year, and the rate

and time profile of conversion of polyps into cancers

and silent cancers into detected cancers.

Estimates of the prevalence of polyps in 65-yearolds and the incidence of new polyps in succeeding

years come from two kinds of evidence: autopsy

studies and randomized screening in populations.

Estimates of the prevalence of adenomatous polyps

in autopsy studies of the elderly range from 40 to 62

percent. (See table 4 in the main report). Estimates

taken from autopsy studies may be biased upward,

because the presence of adenomas may be correlated

with the presence of other diseases (such as atherosclerosis) (71), although this bias may be more serious

in younger age groups. A Norwegian study of

colonoscopy given to over 400 randomly selected

people between 50 and 59 years of age showed the

presence of polyps in 35 percent (69). It is well documented that polyp prevalence increases with age

(145). A higher estimate of polyp prevalence will

increase the estimated cost of CRC screening, which

is unfavorable to screening, so OTA chose an

estimate of 60 percent.

The incidence of new polyps in the elderly is

unknown. New polyps do develop, at least in people

with previously detected polyps. Data from the

National Polyp Study indicate that 30 percent of

patients followed with colonoscopy after polyp

removal had additional polyps (either new or previously missed) within 1 year of a polypectomy (172).

Polyps also are subject to spontaneous regression,

however, particularly in the rectum (70). Autopsy

studies show no consistent increase in the prevalence

of polyps across age groups over 65 (table 4 in main

-37-
38- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

report), which suggests that the incidence of new

polyps is low, but these cross-sectional studies may

reflect inherent differences in polyp incidence among

age-specific cohorts. OTA assumed that the

incidence of new polyps in people who reach the age

of 65 polyp free is so small in relation to the

underlying prevalence at age 65 that it can be effectively considered to be zero. This assumption will

very slightly underestimate the costs of screening, followup and surveillance.

If 60 percent of all 65-year-olds have colorectal

polyps, but only 6 percent of these people will ever

be diagnosed with CRC (134), then only a small

percent of polyps, fewer than 10 percent, will

ultimately progress to cancer. An estimate of the

proportion of polyps that eventually becomes clinically manifest cancer (as measured by the SEER

incidence rates for 1979-1984) can be derived from

the proportion of CRCs that arise from polyps.

Although most experts agree with Morson’s claim

that the “great majority of cancers of the colon and

rectum have evolved through the polyp-cancer

sequence,” (106), there is no direct evidence on the

proportion of cancers arising out of polyps. The

arguments in favor of a high proportion are strong

but indirect (145).

2 In a study of almost 2)000

malignant colorectal tumors, Morson and colleagues

found that 57 percent of very early cancers were

unequivocally located in a benign adenoma (106).

The rest were cancers with no contiguous benign

adenoma. The proportion of cancers found together

with benign tumors declined with the degree of

spread of the cancer, which suggests that cancer cells

rapidly overcome the surrounding benign tissue.

Therefore, 57 percent represents a lower bound on

the proportion of CRCs arising from polyps, because

many of the early cancers unassociated with adenoma may have already overcome the sur-rounding

benign tumor.

3 Because a lower estimate ‘s 1ess

favorable to CRC screening (since it reduces the

opportunity to prevent cancers by removing polyps),

OTA used 57 percent as an estimate of the percent

of cancers arising from polyps. (In contrast, a recent

cost-effectiveness analysis of CRC screening

assumed that 93 percent of all cancers arise from

polyps (39).

If only 57 percent of all newly diagnosed cancers

come from polyps, then at most only about 5 or 6

percent of the polyps present at age 65 are destined

to become clinically manifest CRCs. Of these polyps

that will progress to cancers, it is necessary to

estimate the number of years for the progression to

occur. There is undoubtedly a range of progression

times from polyp to cancer (84), but OTA assumed

that all polyps destined to become cancer would

proceed at a uniform rate. The faster the speed of

progression assumed, the less favorable will the

results of the analysis be toward screening, because

there will be fewer opportunities to detect the polyp

with a screening test before it becomes cancer. The

speed with which adenomas destined to become

cancers actually progress from any specific size to

early cancer is unknown, because adenomas are

generally removed when found. Isolated reports of

adenomas followed when a patient refused treatment

suggest that the elapsed time from first diagnosis of

the polyp to the development of a cancer is in the

range of 5 to 12 years. (106). Since these polyps

existed for some unknown period of time before they

were clinically diagnosed, the true range of time from

the emergence of a polyp to cancer is probably

longer than the observed period. OTA assumed that

polyps destined to become invasive cancers uniformly

take 6 years to reach that point.4

2

Fenoglio and Lane have observed that in autopsy studies, small

areas of isolated cancer cells are frequently found associated with

polyps but virtually never found growing alone on the wall of the

colon or rectum (41). Since CRC is such a common disease, if a

substantial proportion of cancers arose de novo from previously

normal tissue, a greater number of isolated focal points of cancer

would have been seen in autopsies. This suggests that most, if

not all, cancers start as polyps.

3Some pathologists question whether the “evidence” of benign

adenomatous tumor found in the histological studies of cancers is

actually residual polyp or abnormal cellular structures and

secretions that develop in normal tissues as a reaction to the

presence of the cancer. For a discussion of the arguments against

the polyp-cancer sequence, see Castleman (19).

4

The impact of changing the progression rate to three years was

also examined and is reported in the text.
Appendix C--Basis for Cost-E electiveness Analysis of Colorectal Cancer Screening- 39

New cancers arise either from polyps or from the

mucosal tissue of the colon or rectum. The speed of

progression from early to late stage cancer and the

rate at which cancers in given stages become clinically manifest must be estimated from very sparse

evidence. We assume that there are two kinds of

early cancers: those that progress so slowly that they

will never become clinically detected for the

remainder of a person’s life in the absence of

screening; and those that are destined to become

apparent even without screening. The former are

“lifetime latent” cancers; the latter are well estimated

by the SEER cancer incidence rates.

Detection of lifetime latent cancers in a screening

program is an unwanted occurrence. Since clinicians

have no way of differentiating between those cancers

that would have progressed and those that would not,

lifetime latent cancers detected in a screening

program are treated like any other cancer in the

same stage. This treatment has both costs and

medical risks, which must be accounted for.

Estimates of the initial prevalence (at age 65) and

subsequent incidence of lifetime latent CRC that

exists in a general U.S. population are available from

only one study, a review of over 16,000 autopsies conducted at a hospital in California in the 1950s (11).

In that population CRCs unrelated to the cause of

death or to symptoms leading to the hospitalization

were discovered at autopsy at rates of: 5 per 1,000 for

people 60 to 69 years old; 10 per 1,000 for people 70

to 79-year-olds; and 15 per 1,000 for people 80- to

89-year-olds. These rates represent the cumulative

life-time incidence of unsuspected cancers in people

5 They imply that at dying in the three age categories.

most 10,400 cases of lifetime latent cancers would be

present in the 1989 population of 65-year-olds, and in

each subsequent year, an additional 0.05 percent of

the remaining population would have new incidence

of lifetime latent CRC that would not be included in

the SEER incidence data but would be subject to

detection on screening. In keeping with the pessimism of the model, OTA assumed that all of these

5Experts frequently observe that people who die are not representative of those who remain alive. Undiscovered cancers are

likely to be overrepresented in hospital deaths (126).

lifetime latent cancers arise directly from the colon

wall and would therefore not be preventable by

removal of polyps. They are also assumed to remain

early stage cancers for the duration of a person’s life.

Cancers destined to become clinically detected in

the absence of screening spend a certain amount of

time in early or late stages before being diagnosed.

The speed with which cancers destined to be

detected in late stage progress through the early

stage will determine the ability of a screening

program to detect the cancer early. Although there

is no direct evidence on cancer progression rates,

mathematical models developed by Eddy

(33,34,35,39) have assumed that cancers progress

from Dukes’ A to Dukes’ C in an average of three

years. Unlike Eddy’s model, however, OTA’s

analysis does not allow for any variation in the progression rate among cases, but to be unfavorable

toward screening, OTA assumed a very rapid progression rate -- one year -- from early to late cancer

for all CRCs destined to be clinically detected as late

cancers.

In addition to assuming that a cancer remains in

the early stage (Duke’s A and B) for one year, OTA

also assumed that a cancer clinically detected in late

stage would have entered that stage one year earlier,

with no variation among cases. Thus, a late-stage

cancer that is destined to become clinically detected

in a person at, say, age 75 would have a one year

window for detection by screening in its early stage

during the age 73. Were the duration in early stage

assumed to be three years, the cancer would be

detectable by screening in its early stage during the

ages of 71 to 73.

Accuracy of Screening

How does CRC screening alter the detection of

polyps and cancer? Fecal occult blood test (FOBT)

and fiberoptic signoidosocpy (FSIG), the two

screening technologies, each have given levels of

accuracy as measured by sensitivity (the percent of

all people with a disease who test positive) and

specificity (the percent of all people without a

disease who test negative). These test characteristics

can be used to estimate the potential of a given

screening regimen to detect polyps and cancers in

each stage. For example, if FOBT has a sensitivity
40- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

for polyps of 5 percent, then every time a person with

a polyp has an FOBT, he or she has a 5 percent

chance of being identified as positive by the test. The

more frequent the testing, the greater the chance for

detection of the polyp. The sensitivity and specificity

of the screening tests must be estimated for each

group in the population.

Sensitivity and Specificity of FOBT

The sensitivity of FOBT for adenomatous polyps

and cancer has been reported in a number of studies.

Reported FOBT sensitivity can be expected to vary

systematically with the population under study. In

particular, test sensitivity would be higher in symptomatic patients than in asymptomatic populations,

because larger polyps or cancers would be more

likely both to bleed and to cause symptoms. Since

FOBT is being considered as a screening test for

asymptomatic populations, its sensitivity in these

groups is the relevant measure.

Table C-1 summarizes the evidence on the

sensitivity of FOBT for both adenomas and cancers.

As the table demonstrates, studies performed on

asymptomatic patients report substantially lower

sensitivity for polyps than do studies on symptomatic

groups. Demers (28) and Bang (6) determined the

sensitivity of the FOBT in asymptomatic populations

of male pattern workers (a group with high colon

cancer rates). They compared polyps found by

FOBT with those found by FSIG. Demers reported

an FOBT sensitivity for polyps of 3 percent and Bang

computed a sensitivity of 5 percent. An English

study calculated the sensitivity of the FOBT for

adenomas by submitting patients returning for followup after polypectomy to colonoscopy and occult

blood testing (168). Williams reported a sensitivity

of 5 percent.

Several investigators have estimated the sensitivity of the FOBT for polyps in symptomatic populations. In these studies, patients diagnosed with

polyps are given the FOBT, and sensitivity is

determined by counting the number of positive

results. Estimates of FOBT sensitivity for polyps in

symptomatic studies range from less than 10 percent

to as much as 39 percent.

Since most polyps less than 1 cm do not bleed in

considerable amounts, the test will be relatively

insensitive to these smaller lesions (92). As table C-1

displays, FOBT sensitivity for carcinomas and large

adenomas is considerably higher than its sensitivity

for small polyps. For example, in a prospective study

of asymptomatic patients, the FOBT sensitivity for

large polyps (larger than 1 cm) was 11 percent (28).

Smaller polyps are less likely to progress to malignancy, so FOBT’s low sensitivity for small polyps and

higher sensitivity for large adenomas may be

desirable and appropriate for the detection of

potential cancers (145). Since polyps that become

cancer are more likely to grow larger and bleed more

frequently than are other polyps (61,106), they would

be detected more easily by FOBT than would the

vast majority of colonic polyps that would never

progress to cancer.

These considerations suggest that FOBT has a

low sensitivity for polyps that do not progress to

cancer and a higher sensitivity for polyps that do

progress. However, for the results to be unfavorable

to screening, FOBT sensitivity for polyps that will not

progress should be high (because detecting a large

number of polyps will increase costs but not improve

outcomes), while FOBT sensitivity for polyps that

will progress should be low in order to minimize the

potential for preventing cancers. OTA concluded

that an FOBT sensitivity of 10 percent for polyps that

will not progress to cancer is a high estimate, and the

same sensitivity (10 percent) for polyps that will

progress is a low estimate. Therefore, in the pessimistic analysis, an FOBT sensitivity for polyps was

assumed to be 10 percent.

FOBT’s sensitivity for cancer should be higher

than for polyps, and as table C-1 shows, studies

generally confirm this hypothesis. In asymptomatic

patients, FOBT sensitivity for cancer ranged from 25

percent to almost 90 percent, but the high estimate

was based on dehydration of FOBT specimens, a

practice not usually undertaken in routine screening.

Reports of FOBT sensitivity for cancer in symptomatic patients are in the range of 50 to 70 percent.

OTA assumed that FOBT sensitivity for cancer in

asymptomatic patients undergoing screening is 40

percent. This value was applied to cancer at all
Appendix C--Basis for Cost-Effectiveness Analysis of Colorectal Cancer Screening- 41

stages and both lifetime latent cancers and those

destined to become clinically detected. (In contrast,

a recent cost-effectiveness analysis of FOBT

screening assumed a sensitivity of 70 percent for

CRC (8).)

There is little disagreement about the high

specificity of the FOBT. Most investigators have

found a specificity of 98 percent (table C-l). This

value has been computed in studies of both symptomatic and asymptomatic populations. Several

models of cost-effectiveness of CRC screening have

also adopted this value (8,35). Because lower

specificity raises the costs of followup and induces

some medical risk from followup procedures, OTA

used a lower estimate of 90 percent, following the

few studies that report lower specificity (table C-l).

Sensitivity and Specificity of FSIG

The sensitivity of the FSIG depends not only on

its ability to detect disease but also on the length of

its reach into the colon. The FSIG allows for visual

examination of the more distal end of the large

intestine. Selby and Friedman (133) claim that there

is no more accurate standard with which sigmoidoscopy can be compared. They also add that

sigmoidoscopy has complete sensitivity for both

polyps and cancer. Other authorities believe that

FSIG sensitivity is a little lower (35,167). Williams

compared colonoscopy with double contrast barium

emema (DCBE) for the detection of large adenomas

and discovered that the endoscope will miss a few

adenomas. Since the colonoscope and FSIG are the

same tool with different lengths, OTA assumed that

the FSIG would also miss a few polyps. To assure

that the results would be unfavorable to screening,

OTA assumed that the sensitivity of FSIG for polyps

that will not progress to cancer is 98 percent within

its reach and the sensitivity of FSIG for polyps that

will progress to cancer and for cancer itself is 92

percent. The lower sensitivity follows Williams’

estimate of the sensitivity of colonoscopy.

FSIGs are available in different lengths, the most

frequent being 60 cm and 35 cm. It is important to

know how far the FSIG will extend into the large

intestine, because polyps are distributed throughout

the large bowel. The depth of insertion will be the

cut-off point for the detection of polyps. The average

depth of insertion for the 60 cm FSIG is 54 cm and

34 cm for the 35 cm FSIG (14,26,31,133).

The depth of insertion must be related to the

percent of colorectal polyps and cancers within the

reach of the FSIG. OTA assumed that the 60 cm

FSIG can reach the splenic flexure over half the

times inserted and that the 35 cm FSIG can reach

between 50 and 75 percent of the sigmoid colon

(133,167). The distribution of polyps in the large

bowel has been investigated by two methods: autopsy

studies and colonoscopic studies of symptomatic

patients.

In autopsy studies, the distribution of polyps is

computed by noting the location of polyps in individuals who have died from unrelated causes. These

studies focus on the distribution of adenomatous

polyps. Hyperplastic polyps, which many experts

believe are more prevalent than adenomas and are

primarily concentrated in the rectal region (25,133),

are not included. As table C-2 shows, autopsy

studies report that approximately 30 to 50 percent of

all adenomatous polyps lie between the anus and the

splenic flexure. The range for adenomatous polyps

between the mid-upper portion (MUP) of the

sigmoid colon to the anus is from 13 percent to 25

percent. Chapman performed an autopsy analysis on

individuals over 60. He found that roughly 35

percent of adenomatous polyps were below the

splenic flexure and 13 percent were below the MUP

sigmoid colon (21). In an autopsy study of both

hyperplastic polyps and adenomas, 42 percent of all

polyps were below the splenic flexure and 32 percent

were in the lower fifth of the colon (25).

An alternative method for estimating the distribution of polyps is colonoscopy studies of symptomatic

patients. This method may fail to give an accurate

representation of polyp distribution in an asymptomatic population. It is probable that symptomatic

patients suffer from rectal bleeding, indicating that

larger adenomas are present. These studies are

therefore likely to overestimate the presence of

polyps in the lower half of the colon. Estimates of

the percent of polyps below the splenic flexure range

from 56 percent to 77 percent and estimates for

polyps below the MUP sigmoid colon range from 30
42- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

I

I

I

I

I

I

I

I

I

#.1

I

I

I

I

I

I

I

I

I

I

I

I

I I l l I I
Table C-2-Distribution of Polyps by Location From Autopsy Studies of U.S. and Foreign Populations

Right colon Transverse Left colon

Rectal/

Kind of Population Ascending Hepatic Transverse Splenic Descending Sigmoid sigmoid

Study polyp Year studied Country Cecum colon flexure colon flexure colon colon colon Rectum

Helwig, Adenomatous 1943

1943

Blatt, 1961 Adenomatous 1959-

1960

Arminski Adenomatous 1964

and

McLean,

1964

Chapman, Adenomatous not

1963 given

Stemmermann Adenomatous 1969-

and Yatani,

1973

Rickert et al.,

1979

Restrepo et

al., 1979

Correa et al.

1972

Adenomatous Not

given

Adenomatous 1971-

1973

Polyps 1970-

1975

1,460 consecutive

autopsies

446 consecutive

autopsies on adults

=30 years old

1,000 colons of adults

>20 years old undergoing autopsy at

Detroit, Ml hospital

443 consecutive

autopsies in New York

state hospital; polyps

found in adults ›30

202 necropsies in

Kuakini hospital on

Hawaii Japanese adults

518 colon-rectum

specimens recovered at

autopsy in adults ›20

years old, in New

Jersey hospital; excluding

CRC cancer cases

USA

USA

USA

USA

USA

USA

506 colon rectum spec- Colombia

imens recovered at

autopsy in adults ›10

years old in Medellin,

Colombia

463 autopsy cases from 4 USA

New Orleans hospitals

serving poor communities

11.8

18.0

10.0

All:

6.9

> 60:

7.1

10

13.0

16.9

15.4

19.0

19.0

35.1

35.6

34

26.0

23.7

21.0

25.0

11.0 16.0

10.0 11.2

10.3 11.7

22

27.0

20.3

27.0

8 . 1 28.0 16.0

11.0 20.0 7.0

10.0 6.0 : not

included

8.9 6.0 19.2 2.7

9.1 6.7 16.6 2.8

11 15 1 6

9.0 17.2 7.4

8.4

42%* 32 %

b

20.3 10.4

a Percent of polyps from splenic flexure to anus.

b perwnt of poiyps In last fifth of colon.

SOURCE: T. C. Arminski, and D.W. McLean, “lncidenoearrd DiatributionofAdenomatous PolypsoftheOolon and Rdum Sasedon 1,000 AutopeyExaminations, ”fXs. CclorrRecturrr7 :249-261, 1964; L.J. Blatt, “PolypeoftheColon

and Rectum: Incidence and Distribution,” D/s. Colcrrl?ec. 4:277-2S2, 1SS1; 1. Chapman, “Adenomatous Polypi of Large Intestine: Incidence and Distribution,” Anrr. Surg. 157(2):223-226, 1903; P. Corre% J.P. Strong, A

Reif et al., “The Epidemiology of Ccdorectal Polyps: Prevalence in Naw Orleans and International Comparisons,” Cancer 3s:225S-22S4, 1977; E.B. Helwig, “Senign Tumors of the Large Intestine-lnciderra and Distribution,” Surg. GyneooL OMwt. 76:419, 1943. 1S43; C. Reatrepo, P. Corre% E. Duque et al., “Polyps in a lmw-Risk Colonic Population in Columbia South America” /3/s. Colon Rectum, 24:2S-36, 19S1; R.R. Rickert, 0.

Auerbackk, L Garfinkeletal., “Adenomatous Leaionsofthe Large Sowel:An Autopay SuIVey,” Cancer 43:1 S47-1S57, 1979; G.N. Stemmerman and R. Yatani, “Diverticuloaisand Polypaofthe Large intestine: ANeocropsy

Study of Hawaii Japanese,” Oamer 31(5) :12s0-1270, 1973.
44- Costs and Electiveness of Colorectal Cancer Screening in the Elderly

percent to 53 percent (table C-3). In an age-specific

analysis, Grandquist found that approximately 56

percent of polyps in patients 65 years of age and

older were below the splenic flexure and 30 percent

were below the MUP sigmoid colon (59).

As the data presented indicate, there is no consensus on the distribution of polyps in the large

bowel. To be pessimistic toward screening, OTA

assumed that roughly 70 percent of polyps that will

not progress to cancer are within the reach of the 60

cm FSIG and that 30 percent are within the reach of

the 35 cm FSIG. For polyps that will progress, the

reach is assumed to be 35 percent for the 60 cm

FSIG and 20 percent for the 35 cm FSIG.6

Authorities agree that the specificity of the FSIG

is 100 percent (35,133). Since FSIG is based upon

visual examination, the trained examiner will not

mistakenly identify normal colonic mucosa for a

polyp or tumor. To be pessimistic, however, OTA

assumed an FSIG specificity of 95 percent.

Medical Risk of Screening

Detection of a polyp or carcinoma by screening

brings forth the use of medical procedures that have

small but non-negligible risks of complications and

6

In contrast, in a cost-effectiveness analysis of CRC screening for

colorectal cancer in a high risk population, Eddy assumed that 55

percent of the polyps could be detected by the 60 cm FSIG and

40 percent by the 35 cm FSIG (35).

Table C-3- Distribution of Polyps

death. These medical risks, particularly the risk of

death associated with colonoscopy in followup or surveillance and with resection of otherwise lifetime

latent cancer must be accounted for as an adjustment

to screening effects.

Colonoscopy carries with it a small chance of

bowel perforation and, rarely, death. Nevertheless,

when a large number of elderly people is expected to

undergo followup or surveillance colonoscopy, these

risks cannot be ignored. Reported rates of colon

perforation with colonoscopy are in the range of 0.1

percent to 0.2 percent and reported mortality is

between 0.02 percent and 0.05 percent (38,119,142).

OTA used the low end (0.02 percent) of this

mortality range to estimate the death rate from

colonoscopy, because the mortality rates are taken

from studies of symptomatic patients, whereas followup and surveillance would be performed on

asymptomatic people.

Because the standard of care for early cancer is

surgery to remove the cancer, an estimate of the

surgery-induced mortality was also necessary. Operative mortality rates associated with CRC surgery

increase with age (42,145), but improvements in

operative technique in the 1980s have reduced the

operative mortality for all ages (42). A study of

surgery for CRC in elderly patients in England

during the 1970s showed that in-hospital mortality

rates for those over 70 years of age was about 13

percent, but for those between 70 and 79 years of age

whose operations were elective, the in-hospital

in Studies of Symptomatic Patients

Estimated percent of patients’ polyps:

Below splenic Below MUPa

of

Study Kind of polyp Year Population studied flexurea

sigmoid colonb

Tedesco et al., Polyps 1980 Symptomatic 88%

1980

Gillespie et al., Adenomas 1979 Patients with previous 77% 53%

1978 colonic surgery or

colorectal symptoms

Webb et al., Adenomas 1985 Symptomatic 74% 38%

1985

Granqvist, Polyps 1981 Patients >65 years with 56%

1981 intestinal disorders

*MUP = mid-upper portion.

bne OTA dimat~ are calculated from data provided in cited studY.

SOURCE: P.E. Gillespie, T.J. Chambers, KW. Chan et al., “Oolonic Adenomaa-AColonoecopy Survey, - Gut20:24C+24S, 1978; S. Granqvist, “Distribution of Polyps in the Large

Sowed in Relation to Age,” Seend. J. Gesfmenr. 16:1 G2!5-1031, 1SS1; F.J. Tadeeco, J.D. Wayne, J.R. Avella et al. “Dlagnoatic Implieetions of the Spatial Distribution of

Colonic Maee Lesions (Poiypa and Oancere). AProspective Oolonoacopic Study,” Ges@mhtescEmbse. 26(3) :S!5-97, 1SS0; WA. Webb, L McDaniel, and L Jones, “ExpsP

rienca With 1,tXKI Colonoscopic Polypactomiea,” Arm. SUW. 201 :826-630, 19S5.
Appendix C--Basis for Cost-Effectiveness Analysis of Colorectal Cancer Screening- 45

mortality rate was about 8 percent (42). Another

British study found a 6 percent overall surgical

mortality in patients over 70 years of age and a 4

percent mortality after elective operations (75).

Because surgeries for lifetime latent cancers would

be entirely elective, OTA pessimistically assumed an

in-hospital mortality rate of 7 percent.

Years of Life Gained From Screening

The years of life gained from screening the population over time were estimated as the difference

between the years of life lost from CRC in the

absence of screening and the years of life lost under

a screening regimen from: 1) CRC; 2) operative

mortality associated with treatment of lifetime latent

cancers found in screening; and 3) deaths due to

complications of colonoscopy performed in both followup and surveillance. These values change with

age, for the older the person is, the more likely he or

she is to die of other causes, and the fewer the added

years of life that can be expected from screening.

Calculation of the years of life lost due to CRC

was based on assumptions about survival probabilities. Five-year survival probabilities for CRC are

based on observed 5-year survival rates by age and

stage for the elderly provided to OTA by NCI from

the SEER database (124).

Transforming these survival rates into expected

years of life requires additional assumptions about

the shape of the survival curve over time. One

method of approximating life expectancy from 5-year

survival rates (referred to as the “DEALE” method)

assumes that survival probability follows a simple

declining exponential function over time (9,10).

Using this assumption, the five-year survival rate

would be transformed into an annual “mortality

force” which is then used to adjust the life expectancy

of a particular age-group. For example, if the 5-year

survival rate for late CRC were 50 percent in people

65 years of age, the life expectancy of a 65-year-old

newly diagnosed with late stage cancer would decline

from 16.7 years to exactly 5 years. The magnitude of

this calculated decline in life-expectancy due to

cancer seems unduly large.

An alternative method, used by OTA, assumes

that virtually all CRC patients who survive for 5 years

can be considered cured.

7 Under this assumption,

patients who do survive 5 years can be expected to

live out the remainder of their expected years of life.

Those who do not survive are assumed to die in 3

years. Using these assumptions, the expected life of

a 65-year-old newly diagnosed late-stage cancer

patient with a 50 percent 5-year survival rate would

be 9.7 years. Then, for every late-stage cancer prevented, 7 years would be gained, compared with a

gain of 11.5 years under the assumptions of the

DEALE model.8 Because OTA’s method shows less

gain in years of life from the prevention or early

detection of CRC than does the DEALE method, it

is more pessimistic about the effectiveness of

screening than the other method would be.

Treatment of lifetime latent cancers detected

through screening was assumed to offer no benefit in

increased years of life, but surgery-related deaths

were assumed to cost the remaining years of life

expected for people of the age at which the surgery

takes place. Similarly, colonoscopy performed for

surveillance purposes was assumed to have no

benefit, but colonoscopy-related deaths were

assumed to cost the remaining expected years of life.

7Survival probabilities are correlated with patterns of recurrence

of CRC after treatment. In a recent review of the literature,

DeVesa and colleagues reported recurrence rates of CRC by

stage as follows (29): Dukes’ A: 0-13 percent; Dukes’ B: 11-61

percent; Dukes’ C: 32-88 percent. Moreover, 90 percent of all

recurrences become apparent within four years of the initial

operation (29). Of those with recurrent CRC, the median survival is about 8.5 months and over 95 percent of patients are dead

within three years (166). Taken together, these patterns of survival suggest that the vast majority of patients who are alive 5

years after diagnosis of CRC will not experience a recurrence of

the disease.

8

It would also be possible to calculate the number of “healthy

years of life’ gained from cancer screening by assuming that the

quality of life of a person destined to die of CRC within three

years is so low as to not be worth calculating. Using “healthy

years of life” as an effectiveness criterion would increase the calculated effectiveness of screening counteracting the deliberate

bias against finding screening effective.
46- Costs and Electiveness of Colorectal Cancer Screening in the Elderly

The years of life gained and lost from screening

in each year were totaled and discounted to their

present value at the same discount rate--5 percent --

used to calculate the net costs of screening.

9

MEASUREMENT OF COSTS

The unit costs of screening, followup and surveillance procedures were based on average Medicare

Part B allowed charges for such services performed

in the physician’s office in 1988. Table C-4 shows

how these allowed charges varied by specialty in

9The discounting of health effects as well as costs is necessary to

insure that programs whose benefits lie well in the future will not

be found more cost-effective if postponed indefinitely (77).

1986. Gastroenterologists were allowed higher

charges on average than were internists. These

allowed charges do not reflect the full expenditure

for such services, because physicians are not required

to accept Medicare’s allowed rate as full payment but

may bill the patient for the balance between the

physician’s fee and the allowed charge. Over 77

percent of all claims submitted to Medicare in 1988,

however, did involve acceptance of the allowed rate

(121) and almost 40 percent of all physicians agreed

to accept Medicare’s allowed charge as full payment

for all of their Medicare claims (121). Thus,

although some patients may pay more than the

allowed amounts for screening, followup and surveillance procedures, it is reasonable to assume that

such services are widely available in most communities at the allowed rates.

Table C4-Selected Screening, Followup, and Surveillance Chargesa for Colorectal Cancer

Charges

Average of

CPT code Procedure all MDs Gastroenterologist Internist

Screening:

82270 FOBT (office lab) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $ 3.60 - - c

FOBT (independent lab) . . . . . . . . . . . . . . . . . . . . . . . . . .

- -

4.08 —-

FOBT (all settings) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

- -

3.63

Sigmoidoscopy (flexible fiberoptic) . . . . . . . . . . . . . . . . . . 87.53 $ 94.43 $ 85.41

Proctosigmoidoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39.76 - - - -

Diagnostic followup:

45378

74280

88302-

Surveillance:

45378

Colonoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $375.72

Colonoscopy for biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 437.07

Colonosoopy for tumor ablation . . . . . . . . . . . . . . . . . . . . . 449.16

Colonoscopy for polyp removal . . . . . . . . . . . . . . . . . . . . . 626.48

Sigmoidoscopy (flexible fiberoptic)

for biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115.53

Sigmoidoscopy (flexible fiberoptic)

for tumor ablation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162.49

Sigmoidoscopy (flexible fiberoptic)

for polyp removal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143.59

Barium enema, air contrast . . . . . . . . . . . . . . . . . . . . . . . . 97.71

Surgical pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51,37d

Colonoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $375.72

$421.60

461.45

447.89

665.83

127.01

195.04

167.51

- -

$421.60

$350.19

421.38

438.91

586.20

107.94

118.12

143.19

- -

$350.19

ABBREVIATIONS: CPT = current procedural terminology FOBT = fecal occult blood teat.

a Charges used in this table are Medicare average allowed charges for1SS6(117).

b unl~ “ot~ othe~ige, the pla~ of service for all of these pr0@3dunSS is the ph~icien’s o~ce.

c The double degh indicateg that OTA did not request this infO~atiOn.

d lggg ~lo~ Chqe in all plac~ of ~wice ~r a ~ighted a~rqe of surgi~ @ho@y procedure in CPT ~ee -,SS304, 8S305, and 99307,_

SOURCE: Health Care Financing Administration, 198S
Appendix C--Basis for Cost-Effectiveness Analysis of Colorectal Cancer Screening- 47

Accurate estimates of the lifetime cost of treating

CRC in elderly people simply do not exist. Estimates

have to be pieced together from incomplete data

sources, most of which are based on cases occurring

in the 1970s.

Analysts at NCI have used the Medicare Continuous History Sample File, (a record of Medicare

charges incurred by a sample of 1.6 million beneficiaries over an 8-year period from 1974 to 1981) to

estimate the costs of cancer treatment (5). For beneficiaries with diagnoses of CRC, these researchers

estimated charges made to Medicare in three

periods: during the first 3 months following diagnosis; in the last 6 months of the beneficiary’s life;

and during the period between these two phases.

Table C-5 summarizes the average charges made for

the beneficiaries with CRC in the sample.

The Medicare Continuous History Sample (CHS)

file does not tell the stage at diagnosis, so these

estimates are based on a mix of cancer cases. Also,

though the estimates are updated to 1984 dollars,

they are based on a pattern of care that existed in the

1970s and that reflects neither the movement of

cancer care out of hospital settings in the 1980s nor

the development and diffusion of therapeutic

colonoscopy for treatment of very early cancers.

Finally, the estimates include all medical care costs

incurred once a patient has received a recorded diagnosis of CRC, not just those specifically related to

cancer care.

Three cost-effectiveness analyses of CRC

screening have estimated the stage-specific costs of

treating cancers. Allison and Feldman reported on

stage-specific 5-year costs of treating CRC for

Tablet C-5-Average Charges Made to Medicare for

Treatment During the Initial, Continuing, and

Terminal Phases of CRC (1984 dollars)

Initial phase (3 months) . . . . . . . . . . . . . . . . . . . . . . . . $14,190

Continuing (monthly charges) . . . . . . . . . . . . . . . . . . $572

Terminal phase (last 6 months) . . . . . . . . . . . . . . . . . $15,776

SOURCE: M.S. Belter, LG. Keesler, and R.C. Smucker, “SbSpecifk Tmet.ment

Cosis for Cencw An Arre@s of ttre~lcere Continuous tfistorySerm

@e Fih” unpublished, 19SS.

patients first diagnosed in 1974 at the Kaiser

Permanence Medical Plan, a Health Maintenance

Organization in California (l). The Kaiser data are

also based on patterns of care for CRC that were

current almost 15 years ago, and, in any case costs in

this setting of care might not adequately represent

costs in fee-for-service medicine.

Studies of the cost-effectiveness of CRC

screening have made “reasonable” assumptions about

the costs of treating cancer detected in various

stages. In a 1987 analysis, Barry and colleagues

assumed that early cancer treatment would cost

$10,000, while terminal care would cost $20,000. The

cost of treating a perforated colon (a rare complication of colonoscopy) was assumed to be $10,000

(8). In an analysis published in the same year, Eddy

assumed that initial therapy would cost $10,000 for

cancer detected in local stages (Dukes A or B),

$12,000 for cancer detected with regional spread

(Dukes’ C), and $14,000 for cancer detected with

distant metastasis (Dukes’ D) (35). A more recent

analysis by Eddy used higher costs (39).

Table C-6 compares the estimates of the costs of

treating cancers first detected in early and late stages

from four analyses, updated to 1988 prices. Two of

the studies (1,100) are explicitly based on empirical

cost data from very different sources, but the

similarity between the estimates in the four studies is

striking. Only the Barr and Mulley estimates

represent discounted costs1 0 and should therefore be

lower than the other two estimates. However, since

most treatment costs occur soon after detection, discounted costs should not be much lower than

undiscounted costs.

Based on the information presented above, OTA

assumed that the discounted cost of treating early

cancers is approximately $20,000 and of treating late

cancers is $30,000. The results of a sensitivity

analysis of the impact of changes in these two cost

estimates on the net health care costs per year of life

gained are presented in the main body of this paper.

losince ~h~ treatment COSE will occur over time they ‘hould be

discounted to their present value at the time of detection.
48- Costs and Effectiveness of Colorectal Cancer Screening in the Elderly

Table C-6-Estimates of the Cost of Treating Early and Late Cancers in 1988 Dollars

Early cancers Late cancers Difference in cost between

Study (Dukes’ A &B) (Dukes’ C & D) early and late cancers

Eddy, 1966* . . . . . . . . . . . . . . . . . . . $17,723-$21,069 $33,176 $12,067-$15,453

Allison and . . . . . . . . . . . . . . . . . . . . $22,696 $34,516

Feldman, 1974b

$11,817

Barry et al., . . . . . . . . . . . . . . . . . . . . $10,000 $20,000 $10,000

1967C

Mellow, N. D., 1966d . . . . . . . . . . . . . $19,767

-culated from Eddy 1966, using estimated costs of initial care by stage plus costs of terminal care multiplied by the assumed percent dying within 5 years by stage. Costs are

undiscounted.

b@Jcul&ed~mAl}\mnmd Feldm~ usingobge~$~~oft~~ing Cancers bystageintheirstudy population, Coats -updated to l= using medicaicara component of

CPI-U. Costs am undiscounted.

c~m ~ discounted COStS (6 percent rate of discount).

d phWicim ~d h~pit~ chqf~ for bhc@fa/ cam St a l~e Mi~em h~pit~

60URCE: J.E. Allison, and F. Feldman, “Coat Benefita of Hemoccutt 6cmeningfor Colorectal Carcinom%g /llg. Ok. &So/. 30(9):660-665, 1965; M,J. Bany, A.G. Mulley, and J.M.

Richter, “TheEftectof Wodwp6trategyon theCost-Effectiveneeaof Fecal OcdtBlood Screening forColorectal Cancer,” Ge@oentero@y93:301-310, 1967; D.M. Eddy,

“6creeningforColorect.alCancer,- ftxthcoming inAnne/sof/n8srna/A4scfiche; M.H. Mellow, “EndoacopicLsserTreatment of Colon Cancer,” 7kapwUo Gestrohf8stirnll

Endoscopy An /nfonrrefbrr Fbsoume Menua/ (Manchester, MA: Amercian 3ociety for Gastrointestinal Endoecopy, 1966).

The risk of nonfatal bowel perforations was same as the cost of treating early stage cancer

assumed to be 0.1 percent, and the medical cost of ($20,000). Fatal bowel perforations were assumed to

treating these complications was assumed to be the cost as much as treating a late stage cancer ($30,000).
1.

2.

3.

3a.

4.

5.

6.

7.

8.

9.

10.

Allison, J.E., and Feldman, F., “Cost Benefits

of Hemoccuh Screening for Colorectal Carcinoma,” Dig Dis Sci 30(9):860-865, 1985.

American Cancer Society, “ACS Report on the

Cancer-Related Health Checkup,” Cancer

30:194-240, 1980.

American Cancer Society, “Summary of

Current Guidelines for the Cancer-Related

Checkup: Recommendations,” (New York:

ACS Professional Education Publication,

1988).

American College of Physicians, Clinical

Efficacy Assessment Project, “Screening for

Colorectal Cancer,” Philadelphia, PA, April,

1990.

Arminski, T. C., and McLean, D.W., “Incidence

and Distribution of Adenomatous Polyps of the

Colon and Rectum Based on 1,000 Autopsy

Examinations,” Dis Colon Rectum, 7:249-261,

1964.

Baker, M.S., Kessler, L. G., and Smucker, R. C.,

“Site-Specific Treatment Costs for Cancer: An

Analysis of the Medicare Continuous History

Sample File,” unpublished article, 1988.

13ang, K. M., Tillett, S., Hoar, S. K., et al.,

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