to the editor: In their editorial, Drs. Woolf and Ganiats1 state that there is “compelling evidence” and consensus among professional groups that all persons 50 years of age and older should be offered colorectal cancer screening. They also state that “a failure to offer such testing to our patients is to deny them a preventive measure of proven benefit.” I must respectfully disagree that the evidence is compelling. I also submit that the benefit is uncertain.
In each of the three randomized controlled trials of colorectal cancer screening,2–4 colorectal cancer mortality rates were reduced only modestly. The absolute reduction in risk of colorectal cancer death ranged from 0.10 per 1,000 person-years (95 percent confidence interval 0.18 to 0.01) in the Hardcastle study, to 0.22 per 1,000 person-years in the annually screened group in the Mandel study (95 percent confidence interval 0.34 to 0.09). The number needed to screen for eight to 13 years to prevent one colorectal cancer death would be near 700. The upper band of the 95 percent confidence interval would be several thousand. Thus, the chance that an individual who is screened for colorectal cancer will be spared death from colorectal cancer is small—quite possibly less than one in 1,000.
I also believe that the benefit from colorectal cancer screening is uncertain. In none of the randomized trials of colorectal cancer screening has all-cause mortality been reduced. Welch and Black5 have reviewed the importance of considering all-cause mortality when evaluating randomized trials of screening. “To consider whether a reduction in disease-specific mortality is somehow offset by an increase in mortality from other causes, all-cause mortality must be examined.”5 To that end, I have combined the total deaths from the three randomized trials (see table).
|Screening||Number of patients||Number of deaths||Deaths per 1,000 patients|
If the biennially-screened group from the Mandel study is excluded, the all-cause mortality rate in the screened subjects still does not differ significantly from that in the unscreened subjects (182.39 deaths per 1,000 subjects). The evidence indicates that colorectal cancer screening using fecal occult blood testing fails to reduce all-cause mortality. In fact, since colorectal cancer mortality is reduced, it would appear that colorectal cancer screening increases non-colorectal cancer mortality slightly—countering the small benefit of reduced colorectal cancer mortality. Hence, it has not been proven that colorectal cancer screening is truly beneficial. Indeed, Mulcahy and colleagues6 have concluded that there are insufficient data to advocate a colorectal cancer screening program.
I believe that our patients will best be served if we use caution in offering colorectal cancer screening. I suggest that physicians discuss the limited benefit of colorectal cancer screening with their patients, and let them decide if the minimal reduction of risk of colorectal cancer death—and no proven reduction in risk of death itself—is worth the effort, cost and risk of harm from false-positive tests. I recommend informed consent before proceeding with screening.
in reply: We agree with Dr. Budenholzer that the probability of benefiting from colorectal cancer screening is relatively small. We are puzzled, however, by his opposition to our statements that everyone 50 years of age and older should be offered colorectal cancer screening and that failure to offer such testing is to deny our patients a preventive measure of proven benefit. Not offering screening and the accompanying information denies patients the opportunity to decide whether the tradeoff is worthwhile.
We do not overstate the evidence (from three large clinical trials) to say that fecal occult blood testing, likely the least effective of the available screening tests,1 is of proven benefit in reducing colorectal cancer mortality. The absolute risk reduction from fecal occult blood testing is relatively small, but this is because the baseline probability of dying from the disease is low. The chance that a healthy person will eventually die of a specific type of cancer is relatively small. For this reason, although annual fecal occult blood testing lowers the relative risk of dying from colorectal cancer screening by 30 percent, the absolute risk reduction is much smaller.
The same is true for the prevention of most chronic diseases. Those who advocate mammography screening for women aged 40 to 49 do so despite evidence that the probability of preventing a death from breast cancer in 10 years is only about one in 1,500 to 2,500. Other common screening tests (e.g., cholesterol, phenylketonuria, Papanicolaou smears) provide a chance of benefit that is even smaller than that calculated by Dr. Budenholzer for colorectal screening (one in 700 to 1,000).
Dr. Budenholzer also worries that colorectal cancer screening has not been shown to lower all-cause mortality. The same concern has been raised about other preventive measures, such as lowering high blood cholesterol. Are we simply replacing one cause of death with another? We must remember, however, that the trials cited by Dr. Budenholzer were not designed to answer this question. It took over a decade and the participation of over 100,000 patients to amass current evidence that screening lowers colorectal cancer mortality. Detecting an effect on overall mortality would require a much larger sample size and a longer follow-up period. Whether devoting scarce research dollars to the investigation of this hypothesis and not others (e.g., whether prostate-specific antigen screening lowers prostate cancer mortality) represents good public policy is debatable. In the meantime, however, it violates the rules of scientific inference to assert from existing data that screening does not lower overall mortality, or, even worse, to suggest that screening causes non-colorectal cancer deaths.
Whether the modest benefit from mammography or colorectal cancer screening is worth the risk, discomfort and cost is a matter of personal preference. We continue to urge the patient's participation in this judgment.