# Presentation: 857507

## Colorectal Cancer Screening and Surveillance

**FDA Advisory Committee **
**March, 2002**

- David Lieberman MD
- Chief, Division of Gastroenterology
- Oregon Health Sciences University

## Preventing Cancer

**Normal Colon**

**Advanced **
**Adenoma**

- Cancer

## Raising the bar

## Colorectal Cancer ScreeningRecommendations

-  FOBT annual
-  Sigmoidoscopy every 5 yrs
-  FOBT + Sigmoidoscopy
-  Barium Enema every 5-10 yrs
-  Colonoscopy every 10 yrs

- U.S. Preventive
- Services,1995

- Am. Cancer
- Society,2001

- AHCPR
- Multi-discipline
- Panel, 1997

- Am College Gastro
- “Preferred option”,
- 2000

## Fecal Occult Blood Test

- RCT demonstrate mortality reduction (15-33%)
- Easy to perform
- Can be completed by primary providers

## Fecal Occult Blood Test

- Poor sensitivity for one-time test
- Requires repeat testing
- Compliance with repeat testing poor
- Costs are deceptive

## Sigmoidoscopy

**Evidence:**
- Case-Control Studies:
- 60% reduction in CRC
- mortality in the examined
- portion of the colon

## Sigmoidoscopy

**Advantages:**
- - Detects early
-    cancer or polyps
- - Can be performed
-    by primary care
-    providers

**Limitations:**
- - Examines 1/3
-    of colon
- - Proximal lesions
-    may not be
-    detected

## Detection of Advanced Neoplasia: VA Study Data

**Sigmoidoscopy alone:**
- Detection: 70%

- NEJM 2001; 345:555-60

**FOBT alone:**
- Detection: 24%

**FOBT + Sigmoidoscopy:**
- Detection: 76%

**A**

## Barium Enema

-  No Data in screening   populations
-  Miss rate for polyps   > 1cm exceeds 50%   (National Polyp Study)

## Virtual CT

## Virtual MR

## Virtual Colon Imaging

**Attractive name**
- Sensitivity for largepolyps
- Rapid exam

- Cost-effectiveness uncertain
- False positive rate increases cost
- Some patient discomfort
**Small polyp dilemma**

**Advantages**

**Limitations**

## Screening with Colonoscopy

**Advantages**
- Detection of early cancer and advanced adenomas
- Indirect evidence for effectiveness

**Limitations**
-  Risk
-  Costs
-  Resources

## Screening with Colonoscopy

- NEJM 2000;343;162-8 & 169-174

- 			Lieberman		Imperiale
- 			n = 3121		n = 1994
- Age			62.9 yrs		58.9 yrs
- % male		96.8%		58.9%
- % of exams
- complete		97.0%		97.0%
- % with
- Advanced
- Neoplasia		10.6%		7.0%

## Screening with Colonoscopy Evidence for Effectiveness

- National Polyp Study (1993):
- Selby et al (1992):
- Mandel et al (1993 and 2000):

- - Polypectomy reduced cancer incidence

- - Sigmoidoscopy reduced mortality......   in that portion of the colon examined

- - FOBT screened patients had reduced mortality   and incidence

## Summary

- prevalence of advanced neoplasia increases
- prevalence of proximal advanced neoplasia increases
- more patients with advanced neoplasia go undetected with FOBT and sigmoidoscopy
- colonoscopy may be more effective screening test in men after age 60 yrs.

**With increasing age:**

## Colon Screening

**Colon Screening**

- FOBT
- Sigmoidoscopy
- Colon Imaging
- Fecal markers
- Colonoscopy

**Surveillance**
**Colonoscopy**

## Screening Issues

- Surveillance
- Risk
- Cost
- Resources

## Colon Surveillance:Recommendations

- Surveillance accounts for 20-50%
- of cost of colon screening programs

## Neoplasia in Asymptomatic Men

**Neoplasia in Asymptomatic Men**

- Tubular adenoma <1cm		27.0
- Tubular adenoma _>_10mm		 5.0
- Mixed/Villous 			 3.0
**High-grade dysplasia ****	****	**** 1.6**
**Invasive Cancer****	****	****	**** 1.0**

**Among patients with neoplasia, **
**72% had only Tub. Adenomas < 1cm****	**

**%**

- N Engl J Med 2000; 343: 162

**ADVANCED**
**   ****10.6%**

## Surveillance

- Impact on cost of screening program
- Impact on available resources for screening
- Risk Management
- Risk may be low for patients with small adenomas
- Could be reduced with chemoprevention

## Risks of Screening Colonoscopy

- VA Cooperative Study:
- n = 3196 exams
- mean age = 63.0 yrs
- Gender (% male) = 96.8

- Gastrointest Endosc 2002; 55: 307-14

## Risk of Screening Colonoscopy

**Risk of Screening Colonoscopy**

- Gastrointest Endosc 2002; 55: 307-14: VA Coop Study

**Major Complications  (Definite)**
- GI bleed
-     + hosp. or transfusion	7 (6)	0.22%
- Perforation			0
- New Atrial Fib		1
- MI or CVA			4 (2)	0.12%
- Venous Thrombosis		1 (1)
- Other				4

**ALL Definite****	****	**** 9/3196****	****0.3%**
**For Diagnostic only****	**** 2/1435****	****0.1%**
**All complications****	**** 17****	****	****0.53%**

## Risk of Colonoscopy

**Risk of Colonoscopy**

- Significant Bleed
- Prior studies	0.2-1.0%
- VA Coop		0.22 (all therapeutic)
- Perforation
- Prior studies	0 - 0.2%
- VA Coop		0

- Controlling Risk:
-  -  Training
-  -  Quality improvement

## Colon Screening

**Can we afford it ?**

## Cost of not screening

**Cost of Cancer Care**
**Emotional Costs**
**Missed opportunity for prevention**

## Cost of Colon Cancer Screening

- Cost ($)
- per
- added
- year
- of life
- (x 1000)

- Colon	     Hypertension	 Mammography    Cholesterol
- Screening

## Resources: Supply and Demand

**New Demand**

**Capacity**

**Screening**

**Colon**

## Colonoscopy: Indications

**Polyp-Surv**

**+FOBT**

**BRBPR**

**Pain**

**Diarrhea**

**+FHx**

**Screen**

**Cancer**
**  ****Surv**

**Anemia**

**FS/BaE**

**IBD**

**Constip**.

- CORI: National Endoscopic Database  2000-2001

**Current Screening**

## Shifting Resources: Surveillance

**Shifting Resources: Surveillance**

- N Engl J Med 2000; 343:162-8: VA Coop

- 72% of asymp. men with
-   neoplasia had only
- small tubular adenomas

**Can we shift**
**resources from**
**surveillance to**
**screening ?**

- Low Risk of Cancer

## Supply and Demand

**Demand**

**Capacity**

**New Demand**

**Increased capacity:**
**- shift resources**
**- improve efficiency**

## Summary of Screening Guidelines

**	****	****	****	****Potential**
**Strategy****	****Evidence****	****Mortality****	****Limitations**
- FOBT		RCT		20-50%		- Need for repeat testing
- 						- Poor detection of
- 						  advanced adenomas
- Flexible		Case-		50-55%		- Miss-rate for
- Sigmoid (FS)	Control				  proximal neoplasia
- Barium/		none		?? 50-60%	- False (+) rates
- Imaging						- Poor sensitivity
- Colonoscopy	Indirect		70-80%		- Invasive, higher risk

## Intervention

**Intervention**

**Surveillance**

**Advanced Adenoma**

**Cancer**

- Recurrence

- Recurrence

- Possible role of
- chemo-prevention

## Summary of Screening Guidelines

- Effectiveness of any screening program depends on patient compliance
- In 1999, only 44% of adults aged 50 and older had at least one recommended test at appropriate interval  (MMWR, 2001)
- There are many obstacles to colon screening that reduce compliance

## Challenges for the Future

- Identify risk factors for colorectal cancer
- Stratify higher risk patients
- Develop risk-reduction strategies
- Develop new tools to find high-risk patients
- Genetic markers ( in blood or stool )
- Circulating proteins
- New imaging modalities
- Improve patient compliance