10/2/05njm

**Q. When should we start colon cancer screening in low risk adults?**

A. Start colon cancer screening at age 50 years old. See details.

#1

The single best resource for this question is the USPSTF

#### Summary of Recommendations

-   The USPSTF strongly recommends that clinicians screen men and women
    50 years of age or older for colorectal cancer.

> **Rating: [A recommendation]()**.
>
> *Rationale*: The USPSTF found fair to good evidence that several
> screening methods are effective in reducing mortality from colorectal
> cancer. The USPSTF concluded that the benefits from screening
> substantially outweigh potential harms, but the quality of evidence,
> magnitude of benefit, and potential harms vary with each method.
>
> The USPSTF found good evidence that periodic fecal occult blood
> testing (FOBT) reduces mortality from colorectal cancer and fair
> evidence that sigmoidoscopy alone or in combination with FOBT reduces
> mortality. The USPSTF did not find direct evidence that screening
> colonoscopy is effective in reducing colorectal cancer mortality;
> efficacy of colonoscopy is supported by its integral role in trials of
> FOBT, extrapolation from sigmoidoscopy studies, limited case-control
> evidence, and the ability of colonoscopy to inspect the proximal
> colon. Double-contrast barium enema offers an alternative means of
> whole-bowel examination, but it is less sensitive than colonoscopy,
> and there is no direct evidence that it is effective in reducing
> mortality rates. The USPSTF found insufficient evidence that newer
> screening technologies (for example, computed tomographic colography)
> are effective in improving health outcomes.
>
> There are insufficient data to determine which strategy is best in
> terms of the balance of benefits and potential harms or
> cost-effectiveness. Studies reviewed by the USPSTF indicate that
> colorectal cancer screening is likely to be cost-effective (less than
> \$30,000 per additional year of life gained) regardless of the
> strategy chosen.
>
> It is unclear whether the increased accuracy of colonoscopy compared
> with alternative screening methods (for example, the identification of
> lesions that FOBT and flexible sigmoidoscopy would not detect) offsets
> the procedure\'s additional complications, inconvenience, and costs.

[http://www.ahrq.gov/clinic/uspstf/uspscolo.htm](https://mail.southcentralfoundation.com/exchweb/bin/redir.asp?URL=http://www.ahrq.gov/clinic/uspstf/uspscolo.htm)

#2

**Background**

**Average risk**

Expert groups have recommended colorectal cancer screening programs that
resemble each other in most respects. They recommend four options and
their combinations: FOBT, sigmoidoscopy, FOBT + sigmoidoscopy, double
contrast barium enema, and colonoscopy.

In practice, FOBT is the most commonly used screening test followed by
sigmoidoscopy, although screening colonoscopy is gaining in popularity.
The American College of Gastroenterology recommends screening
colonoscopy over other options. Barium enema has not been a popular
screening option, and its use seems to be waning in recent years.

The first step in screening is to determine whether the patient is at
average or increased risk and, if the latter, the specific reason.

If the patient is found to be at average risk, the following
recommendations, prepared by a multi-disciplinary panel convened by the
AHCPR and sponsored by a consortium of gastroenterology societies will
be helpful.

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Offer screening beginning at age 50
years. This recommendation is based upon the rapid rise in colorectal
cancer incidence after age 50, and it is supported by studies that have
found that colonoscopic detection of colorectal cancer is uncommon in
asymptomatic people under the age of 50.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} The patient and doctor should decide
together which set of reasonable options for screening is best for him
or her, armed with information about the effectiveness, convenience,
safety, and cost of each test. The rationale for presenting multiple
options is that no single test is of unequivocal superiority and that
giving patients a choice allows them to apply personal preferences,
which may increase the likelihood that screening will occur.

The following options are supported by strong evidence of effectiveness:

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Offer fecal occult blood screening each
year using a guaiac-based test with dietary restriction or an
immunochemical test without dietary restriction. Two samples from each
of three consecutive stools should be examined without rehydration.
Patients with a positive test on any specimen should be followed up with
colonoscopy.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Offer screening sigmoidoscopy with
flexible sigmoidoscopy every five years. All polyps should be biopsied.
If adenomatous polyps or cancer are found, the patient should be offered
colonoscopy to remove polyps, treat limited cancers definitively, and
examine the entire colon and rectum for synchronous neoplasms. Patients
with tubular adenomas smaller than 0.5 cm should decide with their
physician whether to undergo colonoscopy.

The individual components of the following strategy are supported by
strong evidence of effectiveness, but the additional value of combining
the two, while theoretically present, is not well established by
research evidence:

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Offer screening that includes both FOBT
and sigmoidoscopy (as described above) together. FOBT should be done
first because a positive result is an indication for colonoscopy,
obviating the need for sigmoidoscopy.

The following options seem to be effective when all evidence is
considered, but they are not supported by direct evidence (from
randomized trials, nonrandomized trials, or case-control studies) that
they reduce mortality from colorectal cancer:

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Offer colonoscopy every 10 years.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Offer double-contrast barium enema
every 5 years.

Although all of these options are reasonable, they differ substantially
in ways that matter to patients (such as effectiveness, safety,
convenience, and cost) and none is best on all dimensions. Thus,
patients and their clinicians should decide which is best for them.

**People with a family history of colorectal cancer or adenomatous
polyps**

People with a first-degree relative (parent, sibling or child) with
colon cancer or adenomatous polyps diagnosed at age \<60 years or two
first degree relatives diagnosed with colorectal cancer at any age
should be advised to have screening colonoscopy starting at age 40 years
or 10 years younger than the earliest diagnosis in their family,
whichever comes first, and repeated every five years .

People with a first-degree relative with colon cancer or adenomatous
polyp diagnosed at age
![](media/image2.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}60 years or two second degree relatives
with colorectal cancer should be advised to be screened as average risk
persons, but beginning at age 40 years.

People with one second-degree relative (grandparent, aunt or uncle) or
third-degree relative (great-grandparent or cousin) with colorectal
cancer should be advised to be screened as average risk persons.

  **Rationale** --- Colon cancer screening recommendations based on
familial risk are derived from the known effectiveness of available
screening procedures and the observed colon cancer risk in relatives of
patients with large bowel malignancy and relatives of patients diagnosed
with adenomas at a young age
(![](media/image3.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}60). The risk of colorectal cancer in
close relatives of individuals with adenomatous polyps is still
evolving. Future evidence may better delineate this risk. The rationale
for beginning screening at age 40 in persons with an affected
first-degree relative is that the incidence of colon cancer in such
persons parallels the risk in persons with no family history but
precedes it by about 10 years. Mortality reduction studies directed at
the screening persons with a family history of colorectal cancer or
adenomatous polyps are not yet available. The screening recommendations
given for this group must therefore be considered provisional.

  **New evidence** --- A very large twin study estimated that 35 percent
of all colon cancer cases arose from heritable factors, 5 percent from
shared environmental factors, and 60 percent from non-shared
environmental factors. A meta-analysis examined all studies that
assessed familial risk of colon cancers and adenomatous polyps (27
studies in total) since 1966. The relative risk of colon cancer when a
first-degree relative was affected with large bowel malignancy was 2.42.
Increased risk was found when the relative was affected with either
colon or rectal cancers but was greater for colon. If more than one
relative was affected, the risk was 4.2. The risk was 3.8 for relatives
if colon cancer was diagnosed before age 45, 2.2 if it was diagnosed
between ages 45 and 59, and 1.8 if the cancer was diagnosed at an age
\>59 years. The relative risk for colon cancer if the first-degree
relative had an adenomatous polyp was 1.9, with age effects similar to
those observed for cancer. Another study found that second-degree
relatives (grandparent, aunt or uncle) with colon cancer increased a
person\'s relative risk by about 1.5.

In addition to the genes associated with the rare syndromes of colon
cancer, a number of genes have now been identified that appear to play a
role in this more common but less penetrant category of inherited colon
cancer. Among these are the I1307K APC mutation in Jewish persons of
Ashkenazi descent, the HRAS1- VNTR polymorphism in the general
population, the methylenetetrahydrofolate reductase val/val polymorphism
(protective), and the TGFbetaR-1(6A) polymorphism. These and other genes
may well soon become part of the clinical armamentarium of colon cancer
susceptibility testing but have not yet undergone sufficient evaluation
to be recommended for routine use.

#3

**Extra credit**

At the time of this writing there is are interesting data on a Fecal
Immunochemical Test (FIT). The immunochemical tests are based on human
globin so one doesn\'t need to have patients avoid red meat and
peroxidase containing vegetables. See Morikawa and the Editorial by
Allison below.\*

**Resources**

**Screening for colorectal cancer, UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=screenpm/4407&type=A&selectedTitle=4~89>

**Epidemiology and risk factors for colorectal cancer, UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=gicancer/2331>

**AGA guideline: Colorectal cancer screening and surveillance,
UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=gihepgui/2301>

**Family history of colorectal cancer: Risk, pathogenesis, and
screening, UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=screenpm/7461>

[Morikawa
T](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Morikawa+T"%5BAuthor%5D),
et al. A comparison of the immunochemical fecal occult blood test and
total colonoscopy in the asymptomatic population. Gastroenterology. 2005
Aug;129(2):422-8.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16083699&query_hl=4>

[Allison
JE](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Allison+JE"%5BAuthor%5D).
Colon Cancer Screening Guidelines 2005: the fecal occult blood test
option has become a better FIT. Gastroenterology. 2005 Aug;129(2):745-8.

Abstract\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16083728>

Full text

<http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext>

\*[Morikawa
T](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Morikawa+T"%5BAuthor%5D),
et al. A comparison of the immunochemical fecal occult blood test and
total colonoscopy in the asymptomatic population

BACKGROUND & AIMS: The fecal occult blood test (FOBT) is recommended as
a screening test for colorectal cancer, but there are few reliable
studies on the accuracy of immunochemical FOBT. The aim of this study
was to analyze the sensitivity of immunochemical FOBT and to compare the
results with the findings from complete colonoscopy. METHODS:
Asymptomatic adults underwent 1-time immunochemical FOBT and total
colonoscopy simultaneously. The prevalence and location of colorectal
neoplasia were determined by colonoscopy. The results of immunochemical
FOBT and the colonoscopic findings were compared. RESULTS: Of 21,805
patients, immunochemical FOBT was positive in 1231 cases (5.6%). The
sensitivity of 1-time immunochemical FOBT for detecting advanced
neoplasia and invasive cancer was 27.1% and 65.8%, respectively. In
addition, the sensitivity for invasive cancer according to Dukes\' stage
showed 50.0% for Dukes\' stage A, 70.0% for Dukes\' stage B, and 78.3%
for Dukes\' stages C or D. The sensitivity for detecting advanced
neoplasia at the proximal colon was significantly lower than that
detected in the distal colon (16.3% vs 30.7%, P = .00007). CONCLUSIONS:
Although the screening of asymptomatic patients with immunochemical FOBT
can identify patients with colorectal neoplasia to a certain extent, the
sensitivity is relatively low and different according to the tumor
location. Therefore, programmatic and repeated screening by
immunochemical FOBT may be necessary to increase sensitivity for
colorectal cancer detection.

[Allison
JE](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Allison+JE"%5BAuthor%5D).
Colon Cancer Screening Guidelines 2005: the fecal occult blood test
option has become a better FIT

In this issue of Gastroenterology Morikawa et
al[[1]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib1%23bib1)
present important data on the performance characteristics of a new fecal
immunochemical test (FIT), Magstream 1000/Hem SP (Fujirebio Inc, Tokyo,
Japan), in a large, average risk Japanese population. They used the
Magstream 1000/Hem SP automated system (Fujirebio) and determined
sensitivity, specificity, and positive predictive value by performing
colonoscopy on all patients regardless of FIT result. The overall
positivity rate was 5.6%. The sensitivity of the FIT for colon cancer
was 66% and 20% for polyps \> 1 cm. A 66% sensitivity for cancer is a
marked improvement over the colonoscopy confirmed 13%--39% sensitivity
reported for the most commonly used guaiac test (GT) Hemoccult II
(Beckman Coulter, Inc, Fullerton,
CA).[[2,3]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib2%23bib2)
It is remarkably similar to that reported for the FIT HemeSelect
(69%).[[4]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib4%23bib4)
The FIT, FlexSure OBT, has been shown to have a better sensitivity than
Magstream for left-sided cancers (82%) and left-sided polyps \> 1 cm
(25%) when patients with both positive and negative results were
sigmoidoscoped.[[5]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib5%23bib5)

The problems with the study design are dealt with well in the Discussion
section of the manuscript. They are all offset by the valuable
information this study offers on the performance characteristics
(verified by a "gold standard" endoscopic exam) of another FIT. Before
FIT development only GT were available. GT detect any peroxidase
activity in the feces. Heme either as intact hemoglobin or free heme has
peroxidase-like activity therefore, in the presence of heme and a
developer (hydrogen peroxide), guaiac acid is oxidized producing a blue
color. Heme is present in red meat, and peroxidase activity is present
in fresh fruits and vegetables such as radishes, turnips, and broccoli.
These foods, therefore, have the potential to produce false-positive
results. Although there are several available guaiac tests only 2,
Hemoccult II and Hemoccult Sensa, have been extensively evaluated in
large screening populations. Accurate interpretation of results for GT
requires training and supervision especially when interpreting
borderline
results.[[6--8]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib6%23bib6)
Results are affected by vitamin C, which inhibits the guaiac
reaction.[[9]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib9%23bib9)
The person screened is required to be on a red meat and
peroxidase-containing, food-free diet and to collect the stool sample in
the dry state sampling the feces with a wooden stick. All these
requirements limit patient acceptance and make interpretation of test
results questionable except in well-run laboratories. In a group of
motivated volunteers in an Australian population where red meat
consumption is relatively high, a restrictive diet reduced participation
by
13%.[[10]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib10%23bib10)

The fecal immunochemical tests (FIT) address many of the weaknesses of
the GT. They have superior sensitivity and
specificity.[[4,5]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib4%23bib4)
The application sensitivities for cancer are good (66%--82%) but for
polyps \> 1 cm they are more modest; however, the use of a program of
fecal occult blood test (FOBT) screening (in which screening is
performed yearly or every other year) may result in a cumulative
sensitivity of the program that is competitive with a program of a more
sensitive test performed less frequently. Specifically, a combined
program of FOBT plus sigmoidoscopy may be as effective as or more
effective than a program of colonoscopy screening every 10
years[[11]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib11%23bib11)
because improved FOBT tests such as FIT are more sensitive than the
widely used Hemoccult II. The suggestion of some experts that FOBT
screening should be seriously considered by physicians, patients, and
policy
makers[[12]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib12%23bib12)
should now make the case for FOBT even stronger. The FITs efficacy in
decreasing colon cancer mortality and incidence has not been studied in
randomized controlled trials but, Fletcher has pointed out that if new
screening tests are truly more accurate than GT (Hemoccult II), their
effectiveness need not be confirmed by randomized controlled trials
because Hemoccult II's ability to save lives from colorectal cancer has
already been
shown.[[13]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib13%23bib13)

FITs use antibodies specific for human globin and are, unlike the GT,
specific for colorectal bleeding and not affected by diet or
medications. Some can be developed by automated developers and readers.
This innovation allows for managing large numbers of tests in a
standardized manner with excellent quality assurance. There is evidence
that FIT use improves patient participation in screening for colorectal
cancer.[[14]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib14%23bib14)
Some new technology FITs are able to quantify fecal hemoglobin allowing
for adjustment of sensitivity, specificity, and positivity rates when
screening for colorectal
neoplasia.[[15]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib15%23bib15)
The developing instrument for some FITs has the ability to read a bar
code on the test. This ensures accurate identification of the person
screened and allows for a print out of the result, as well as a reminder
print- out for future compliance. When these innovations have been
perfected and tested in large asymptomatic populations, government
agencies or individual health plans will be able to decide what
positivity rate their budget and manpower resources can accommodate and
still have good sensitivity and specificity for advanced neoplasms in an
annual screening program. Australia has initiated a colon cancer
screening program using InSure and Magstream 1000/ Hem SP and the United
Kingdom and Canada are considering the use of FITs in their screening
programs. Japan has been using FITs successfully for years.

The new and improved FIT choices are now available and reimbursable by
CMS at \$22 per test (includes completed test card with 2 samples and
analysis). In 2004, CMS concluded that adequate evidence existed to
determine that the immunoassay fecal occult blood test (FIT) is an
appropriate and effective colorectal cancer screening test for detecting
fecal occult blood in Medicare beneficiaries aged ≥50 years. The CMS
reimbursement decision has lead to the appearance of several FITs
approved by the FDA for marketing in the United States which, in
addition to InSure (Enterix USA, Inc, NJ), include Instant-View (Alpha
Scientific Designs, San Diego, CA), immoCARE (Care Health Technologies,
Ltd, Waterbury, CT), MonoHaem (Chemicon International, Inc, Temecula,
CA), and Clearview Ultra-FOB (Inverness Medical, Newton, MA). FlexSure
OBT (Beckman Coulter, Palo Alto, CA) will soon reappear as Hemoccult-ICT
(Beckman Coulter Inc, Primary Care Diagnostics, Los Angeles, CA).
Magstream 1000/Hem SP (Fujirebio Inc, Tokyo, Japan) is marketed in
Australia and Europe (Bayer Diagnostics, Tarrytown, NY) as Bayer Detect
and is also likely to be marketed in the US. These tests differ in the
methods used for stool handling and sampling, how (automated or
laboratory technician) and where (office or laboratory) the tests are
developed. Only FlexSure OBT, HemeSelect, InSure, and now
MagStream1000/Hem SP have been evaluated in large numbers (thousands) of
average risk patients with results published in US peer-reviewed
journals.

Despite all the data cited above, clinicians, patients, and the lay
press may still dismiss choices other than colonoscopy for colon cancer
screening because of statements that other tests may miss 25%--65% of
advanced neoplasms. I would answer as follows:

1

All the most recent screening guidelines recommend a menu of screening
options that include
FOBT.[[16--18]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib16%23bib16)
Furthermore, and very importantly, the United States Preventive Services
Task Force (USPSTF) in 2002 concluded that the 2 most effective
screening strategies were annual fecal occult blood testing and
sigmoidoscopy every 5 years or colonoscopy every 10 years. In other
words, a strategy using the currently available less-sensitive version
of FOBT (HOC II) is already competitive, at the individual patient
level, compared with a program of colonoscopy screening, thus any
improvement in application sensitivity would correspondingly improve
such a
program.[[11]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib11%23bib11)
The Task Force found that 5 multiple-strategy analyses did not uniformly
find that colonoscopic screening was the most effective or cost
effective strategy. Similar conclusions were reached by members of the
Institute of Medicine and the National Research Council in a workshop
conference held on the Economic Models of Colorectal Cancer Screening in
Average-Risk
Adults.[[19]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib19%23bib19)

2

Colonoscopy is only one of several good tests available for colon cancer
screening, and we have been cautioned about assuming a screening
colonoscopy is as good as
gold.[[20]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib20%23bib20)

3

Advanced colonic neoplasms consist of a range of lesions (from large
tubular adenomas to early adenocarcinoma) that vary widely in terms of
the risk of progression to fatal cancer. Large polyps (\>1 cm) become
colorectal cancers at a rate of roughly 1% per
year.[[21]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib21%23bib21)
A large polyp, left in situ, has a cumulative risk of malignancy at 20
years of only
24%.[[22]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib22%23bib22)
The development of invasive cancer from a small (\<10 mm) adenoma is
extremely unlikely in less than 5
years.[[23]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib23%23bib23)
Since most polyps, even the "advanced" ones, do not directly lead to
death from colon cancer, the most important value of one test over
another is the incremental benefit of mortality reduction that test
confers to the patient being screened. If screening tests other than
colonoscopy are used as directed, that incremental benefit of
colonoscopy is small.

4

A screening colonoscopy doesn't immunize a patient from getting or dying
from colon cancer for 10 years. Colonoscopy has a significant miss rate
of its
own,[[24--27]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib24%23bib24)
and a program strategy of FIT might be able to uncover both the
colonoscopy misses and the fast-growing
lesions.[[28]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib28%23bib28)
Flat or depressed adenomas may progress more rapidly than polypoid
adenomas to cancer, and flat adenomas and cancers are easy to miss
during conventional endoscopy; their true incidence in the West has yet
to be
determined.[[29]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib29%23bib29)
As the Task Force points out, if cancers most likely to be fatal are
those which develop and grow rapidly, there is an advantage to a
screening program that allows multiple chances to detect an existing
lesion rather than once every 10 years as currently recommended for
colonoscopy
screening.[[11,12,19]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib11%23bib11)

5

Evidence suggests the manpower necessary to provide a skilled
colonoscopic examination for all eligible US citizens is
inadequate.[[30,31]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib30%23bib30)
Unqualified examiners could absorb the overflow and the increased
inaccuracy and complications could undo the small incremental benefit
that the test
offers.[[32]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib32%23bib32)
The millions who undergo screening for no apparent gain are subject to
harms that could cumulatively outweigh the benefits to the smaller group
(those found to have advanced neoplasms) especially if the added benefit
is not very great compared with other screening
options.[[32,33]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib32%23bib32)
The serious complication rate in the VA study where the endoscopists
were all very skilled was 10/3000 or 1 in 300 including a
cerebrovascular accident (CVA) and a myocardial infarction
(MI).[[34]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib34%23bib34)

6

The costs of population screening with colonoscopy are particularly
worrisome at a time when our federal deficit is projected to hit a
record \$477 billion, and there are other worthy causes (prescription
drug benefits, screening for breast cancer, childhood vaccinations,
etc.) competing for health dollars. In the United Kingdom, policy-makers
have written that population screening by colonoscopy is a nonstarter
for the foreseeable
future.[[35]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib35%23bib35)
The UK has neither the manpower nor the necessary facilities to
undertake such screening and their experts estimate the complication
rate arising from screening 171,000 people aged 60 years using
colonoscopy would be unacceptable (over 500 cases of severe hemorrhages,
over 150 perforations, and 50 deaths each year). If history is any
lesson, the current reimbursement for colonoscopy is unlikely to remain
stable or increase. For flexible sigmoidoscopy the rate became too low
to justify the required equipment, staff time, and dedicated
space.[[36,37]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib36%23bib36)

7

The early promise of a fecal DNA test for
screening[[38]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib38%23bib38)
has not been realized in large multicenter trials where this test was
compared with the GTs, Hemoccult II, and Hemoccult
Sensa.[[2,3,39]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib2%23bib2)

It is not realistic to believe any colorectal cancer screening test will
ever detect all advanced neoplasms. As Fletcher has pointed out,
clinicians should be prepared to miss some cancers because many other
factors such as complications, inconvenience, discomfort, cost
effectiveness, and the workforce needed to perform procedures are also
in the balance when deciding which screening policies make the most
sense.[[40]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib40%23bib40)
The best screening test is the one that gets
done.[[41]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib41%23bib41)
The choice of screening tests should be suited to the screening
situation. All the recommendations for a FOBT option in colon cancer
screening guidelines were made on the basis of findings from randomized
controlled trials using GT. If, as it appears, the FIT has better
performance characteristics than the GT, that is compelling evidence for
recommending its use as the FOBT of choice in colon cancer screening
programs.[[42]{.underline}](http://www.gastrojournal.org/article/PIIS0016508505011960/fulltext#bib42%23bib42)
Screening programs involving new FOBTs deserve serious consideration as
a part of our armamentarium of tests for CRC screening.