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 CANCER SCREENING Powered By Docstoc


The public fears cancer and cancer effects everyone if not directly, indirectly. Therefore
in this emotionally charged field it is important to first do no harm. In screening, doing
“everything we can” may not be in our patient’s best interest. Personally, I have been
approached by many a patient with requests such as: “my aunt died of ovarian cancer so
I’d like to have my CA125 checked”, or “I just quit smoking; I’d like a chest xray just to
make sure I’m OK”, or “My cousin was diagnosised with breast cancer; I’d like the
genetic test BRCA”. “I would rather be safe than sorry” is an actual quote from a patient.
In fact, inappropriate screening can actually be harmful.

The purpose of this talk is to advocate for the judicious and appropriate use of cancer
screening. I will discuss controversial aspects of the cancer screening process for the
purposes of better understanding as opposed to finding a resolution.


Demonstrate that screening tests can are not without potential harm.

Describe the challenges inherent to Ca screening: Interval tumors, false positives,
ambiguous results, and pseudodisease.

Show how the 5 year survival rate can be a misleading statistic.

Describe what makes a valid and appropriate screening test.

Show examples of good and bad screening tests.

Advocate for informed decision making and review the US task force recommendations.

Tests can be harmful

Logically, it makes sense. Early detection = Better outcome.
“Early detection saves live” is the message used by the media of both private and public
health care industries to promote various forms of testing for all kinds of diseases.
Implied, is the notion that if you are going to get cancer it is better to find out about it
earlier than later. This may be true in some cases it may not be true in all cases.

In my current practice as an Air Force Family Physician I devote a substantial amount of
time, resources, and energy into the (PHA) Preventative Health Assessment. The PHA
includes a battery of questionnaires, exams, and screening tests (including CA screening
such as PSA for men over 40, annual total body skin exams and testicular exams).
Is the time and are the resources devoted to CA screening in the PHA worthwhile?
Can it actually be harmful by creating angst and distracting us from issues of real
Is the Air Force following evidence based standard of care cancer screening guidelines?
These are some of the questions I would like address during this discussion.

Some of the difficulties in CA screening include:

Interval CA
False positives
Ambiguous results

Interval Cancers

Screening tests are good at detecting slow growing tumors. Unfortunately, often the most
aggressive and lethal cancers are fast-growing. These cancers will have a short preclinical
phase and are therefore difficult to pick up on screening exams. Cancers that appear
between screening tests are called interval cancers. Screening tests tend to miss the
deadliest cancers, the interval cancers.

False +

Generally speaking a screening test has a higher probability of being a false positive than
actually being cancer.
Investigators at UCSF report a false positive rate of 6-7 % for first-time mammography.
(14 p.39) False positive rate for PSA 7-11% (14 p.40)
FOBT false positive rate 8-16% (14 p.40)

Overtime with regular screening, the cumulative risk of a false positive will increase.
See chart (slide) of false positive rate (14 p.43)

Ambiguous results

Unfortunately screening tests are not always black and white. There is not a single
operational definition of cancer. There is a spectrum of cell abnormalities and
pathologists may have different interpretations.

Study published in the American Journal of Surgical Pathology asked 5 experienced
pathologists to evaluate 17 proliferative breast lesions (ten ductal, seven lobular). In no
single case did the pathologists arrive at he same diagnosis. In 33% of the cases the
diagnosis spanned the spectrum from hyperplasia without atypia to carcinoma in situ. (8)
In an Article published in American Journal of surgical pathology 7 pathologists
reviewed 25 cases. When asked to classify the cases into three categories there was
agreement in only 14 of the 25 cases. When asked to stratify the cases into 6 categories
there was total agreement in only one case. (3)

In an article titled “Discordance in the histopathologic diagnosis of melanoma and
melanocytic nevi between expert pathologists” 8 pathologist were asked to review 37
slides. There was complete agreement on only 13 of the specimens. (4)

Published in the Journal of the National Cancer Institute “Statewide Study of Diagnostic
Agreement in Breast Pathology” demonstrated disagreement in 8/30 cases. (12)

Ambiguous results and abnormal results require Confirmatory tests. In some cases this
can lead to a cycle of more and more testing. For example, an ASCUS pap may never
clear. I have had patient who have undergone serial paps and colposcopies and continue
to have ASCUS results.

In today’s culture of fear and malpractice, there is every incentive for radiologist and
pathologists to overcall a reading or diagnosis. When in doubt, it is safer to call it cancer
then to be “negligent”.


Prostate CA. is an example of a tumor that is often non-progressing. By this graph you
can see that virtually all males that live into old age will develop some degree of prostate
cancer. Although millions of men may have prostate CA, only 40,000 die annually for it.
Aggressively treating slow growing tumors on asymptomatic older men can provide little
or no benefit and may cause harm. (7)

Neuroblastoma is a childhood tumor that often will regress. In 1981 large scale screening
programs were launched in Japan, Quebec and Canada.
Urine testing (vma/hva) was used to detect asymptomatic neuroblastomas in infants.
Despite early detection and surgical intervention there was however no decrease in
mortality. As it turns out many varieties of this tumor will naturally regress.
Screening increased detection, more cancers were treated more, but there was no
improvement in the neuroblastoma mortality rate. There were more deaths from treating
screening-detected neuroblastoma than from the disease itself. (7)

Risk of unnecessary treatment

The cancer may spontaneously regression.
Some cellular abnormalities do not progress.

The more you look the more you will find
An Article from Annals of internal medicine which examined autopsy data to estimate
the reservoir of undiagnosed DCIS (ductal carcinoma in situ) suggests that there are a
substantial number of cases of DCIS undetected during life. Pathologists with higher
levels of scrutiny found more disease. (12)

Some experts view the over-diagnosis and treatment of ductal carcinoma in situ (DCIS)
as a potential adverse consequence of mammography.

Although the natural history of DCIS is variable, many women in the United
States are treated aggressively with mastectomy or lumpectomy and radiation. 2
Given the dramatic increase in the incidence of DCIS in the past two decades
(750 percent) and autopsy series suggesting that there is a significant pool of
DCIS among women who die of other causes,3 screening may be increasing the
number of women undergoing treatment for lesions that might not pose a threat
to their health. (U.S. Preventive Services Task Force)

5 year survival can be a misleading statistic

News and the media often quote improvements in 5 year survival to advocate for
screening or treatment. 5 year survival can be a valid measure to compare cancer
therapies in a randomized trial, however comparisons of 5-year survival across time and
place can be misleading.

A study published in JAMA titled “Are increasing 5-year survival rates evidence of
success against cancer?” used population-based statistics reported by the National Cancer
Institute Surveillance, Epidemiology, and End Results Program (SEER) to calculate the
change in 5 year survival from 1950 to 1995 for the 20 most common solid tumors. They
then correlated changes in 5 year survival with changes in mortality and incidence.
Results demonstrated an increase in 5-year survival for each of the 20 tumor types while
mortality rates declined for 12 types of cancer and increased for 8 types.

Increasing 5 year survival rates can reflect changes in diagnosis to include detecting a
cancer in patient who may never be affected by that cancer. The SEER study
demonstrates that there is little correlation between the change in 5 year survival and the
change in tumor related mortality. The 5 year survival rate was positively correlated with
the change in the tumor incidence rate demonstrating that it is a better marker for tumor
detection than tumor survival. (15)

Ideal screening test

A screening exam is a test on asymptomatic persons for the purpose of finding a disease
early in order to intervene and decrease mortality.

Screening is a preliminary test to determine who needs further screening

The accuracy of a screening test is based on four indices: sensitivity, specificity, positive
predictive value, and negative predictive value.
The most beneficial screening tests will target a cancer that has a high prevalence.

Dr. Kramer from the division of cancer prevention at the National Cancer Institute
recommends that the following 5 Criteria for screening test be met before a screening test
is considered for public use (5):

   1)   The test and subsequent follow-up must be acceptable to screening candidates.
   2)   There must be significant burden of disease in the population
   3)   The preclinical stage of disease must be recognizable and prevalent.
   4)   Curative potential must exist primarily at early stages of disease.
   5)   Treatment at early stages of disease must improve outcome as measured by cause-
        specific mortality. (Not simply survival from the time of diagnosis).

Example of Lung CA as a poor screening test

The USPSTF found fair evidence that screening with LDCT, CXR, or sputum cytology
can detect lung cancer at an earlier stage; however, the USPSTF found poor evidence that
any screening strategy for lung cancer decreases mortality. Because of the invasive nature
of diagnostic testing and the possibility of a high number of false-positive tests in certain
populations, there is potential for significant harms from screening. Therefore, the
USPSTF could not determine the balance between the benefits and harms of screening
for lung cancer. (US preventative services task force).

Example of Mammography as good screening test BSE is not.

HIP Health Insurance Plan of New York Study (27) demonstrated a reduction in breast ca
mortality and no change in mortality from other causes with the use of mammography as
a screening exam. The HIP study started in the 1960’s enrolled about 60,000 women aged
40-64 and randomized them into two equal groups. One received mammography and the
other did not. After 10 years 192 died of breast ca in the unscreened group and 147 in the
screened group. Therefore 45 women avoided breast cancer death because of screening.

   The U.S. Preventive Services Task Force (USPSTF) recommends screening
   mammography, with or without clinical breast examination (CBE), every 1-2 years for
   women aged 40 and older.

        Rating: B recommendation.

With the promotion of breast cancer awareness, (BSE) breast self exams are advertised
and encourage by many providers and educators in the health care industry. In my clinic
we hand out pamphlets on how to do self breast exams and there in a poster in the waiting
area reminding woman to do their own self breast exam monthly. It is worthwhile to note
that BSE have not been proven to reduce morbidity and mortality from breast cancer.
Clinicians who advise women to perform BSE or who perform routine CBE to
screen for breast cancer should understand that there is currently insufficient
evidence to determine whether these practices affect breast cancer mortality,
and that they are likely to increase the incidence of clinical assessments and
biopsies. (US preventative services task force).

The efficacy of the FOBT has been proven; however controversy exists on how to
screen for colon cancer.

In 1993 Minnesota Colon cancer control study randomly assigned 46,551 participants 50-
80 years old to three groups. Group one screened for colon ca once a year with FOBT.
Group two screened every two years, and a control group did not screen. There was a
reduced mortality in the annually screened group that was accompanied by improved
survival in those with colorectal cancer with a shift to detection at an earlier stage of
cancer. In this study, annual fecal occult-blood testing with rehydration of the samples
decreased the 13 year cumulative mortality from colorectal ca by 33%. 2% of patients
with a positive test had cancer; thus for every patient with cancer, 50 patients were
subjected to anxiety and further testing.

The USPSTF strongly recommends that clinicians screen men and women 50 years of age or
older for colorectal cancer. This is an A recommendation. I

       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.

The National Polyp Study Work Group followed 1418 patients in who complete
      colonoscopy led to the removal of one or more polyps in the colon or rectum.
      During a mean follow-up of 6 yrs, the incidence of colon cancer was 88-90 %
      lower than in patients who had apparently similar risk but in whom polyps were
      not removed and 76% lower than the general population.

This study estimated that 76 percent to 90 percent of cancers could be prevented by
colonoscopic surveillance exams. However, these results should be interpreted with
Caution because they are based on historical controls and trial participants had more
Complete polyp removal than may occur in the screening setting. There is no direct
evidence the colonscopy reduces ca mortality in people without symptoms or known

The American College of Gastroenterology now considers colonscopy the preferred
screening test, but other expert groups simply list it as an option.
Evidence for effective for effectiveness is strongest for FOBT and weakest for
colonscopy while the potential effectiveness is lowest for FOBT and highest for

The American Cancer Society recommends screening people at average risk for
colorectal cancer beginning at 50 years of age by:

   1.   FOBT annually.
   2.   Flexible sigmoidoscopy every 5 years.
   3.   Annual FOBT plus flexible sigmoidoscopy every 5 years.
   4.   Double-contrast barium enema every 5 years.
   5.   Colonoscopy every 10 years.27

The American Cancer Society does not recommend DRE as a stand-alone
screening test for colorectal cancer. Similar recommendations are issued by the
American College of Surgeons, the American College of Obstetricians and
Gynecologists, and the American Academy of Family Physicians.28-30 The
American Gastroenterological Association, as part of a consortium of related
professional organizations, also issues similar recommendations, which are
currently being updated.3 The American College of Physicians—American
Society of Internal Medicine does not have current guidelines on screening. 5 The
Canadian Task Force on Preventive Health Care concludes that there is good
evidence to recommend annual or biennial FOBT and fair evidence to
recommend sigmoidoscopy as part of the periodic health examination in
average-risk adults after age 50 years; evidence is insufficient to recommend for
or against colonosopy or combined FOBT and sigmoidscopy

Individual risk determination

Before deciding how to screen, clinicians should decide whether the individual patient is
at average or increased risk.

Informed decision-making

“Especially in the emotionally charged field of cancer screening, which can have
substantial public health implications for large numbers of healthy, asymptomatic people,
it is important to achieve strong levels of evidence before promulgating new screening
                  Barnett S. Kramer, M.D., MPH
                  Office of Disease prevention, NIH
US preventive task force recommendations
skin                    I; insufficient evidence for total body skin

prostate                 I; insufficient evidence for PSA or DRE

breast                   B; mammo w/ or w/o CBE q 1-2 yrs
                         I; CBE alone
cervical                 A; pap q1-3 yrs @ 21 or sexually active
                         D; pap not recommended @ > 65 yrs
lung                     I; poor evidence than any screen reduces
colon                    A; FOBT reduces mortality. Insufficient
                         evidence to determine which screen in best
pancreatic               D; against screening in asymptomatic

testicular               D; harms of screen exceed potential benefit