When it comes to cancer screening, more isn't always better.
The U.S. Preventive Services Task Force has announced new mammography guidelines this week. While the task force previously encouraged screenings for women beginning at 40, it has now pushed the threshold to 50. Concerns over frequent false positives and patient anxiety influenced the group's recommendation. Though many believe that there can never be enough testing, a 2004 "Medical Examiner" by Amanda Schaffer explained that the risks of false positives, overdiagnosis, and overtreatment are real. The article is reprinted below.
Americans are enormously committed to cancer screening. In a national survey recently published by Dr. Lisa Schwartz and co-authors in the Journal of the American Medical Association, 87 percent of respondents agreed that "routine cancer screening is almost always a good idea," and 74 percent felt that early detection saves lives "most or all of the time." In fact, so enthusiastic were the survey participants that 73 percent of them said they would rather receive a free full-body CT scan than $1,000 in cash. What to make of these dramatic findings? Clearly, years of strong, scare-oriented public health messages, particularly with regard to breast cancer screening—"Don't be a victim" and similar slogans—have gotten through to the public. The dogma that more is always better when it comes to cancer screening has taken hold, undiluted by any sense of screening's drawbacks.
Yet there are drawbacks—ranging from the risk of false positives to the more complex issues of overdiagnosis and overtreatment. While early detection can certainly have benefits, it's not true that screening can only help—and can't hurt. Indeed, skeptics within the medical community, including the authors of the JAMA survey, have started to become more vocal in an effort to create a more balanced public view.
There are many types of screening, some of which are well-known: mammograms to test for breast cancer, Pap smears for cervical cancer, PSA tests for prostate cancer, fecal occult blood tests for colon cancer, and chest CT scans for lung cancer. What these tests have in common is that they look for early warning signs, including small cellular abnormalities, in healthy, asymptomatic people—sometimes as part of a checkup, sometimes as part of a public-outreach program. Most tests are suggested to patients based on age and gender—PSA tests for older men, mammography for older women. (More "comprehensive" testing is also available for the worried well through executive health programs and at medical boutiques in strip malls, where patients can undergo full-body CT scans, an aggressive form of testing generally disdained by doctors.) But just what are the risks associated with testing? Isn't more information, particularly about the vagaries of the body, always a good thing?
A Risk of False Positives
This is probably the most familiar problem associated with routine screening: Tests sometimes yield a positive result in a person who does not have cancer. Consider, for instance, PSA screening for prostate cancerin men over the age of 50: 15 percent will have elevated PSA levels while only 3 percent will in fact have cancer; that is, 12 percent will receive a false-positive result. Or consider lung cancer screening for former smokers: Between 25 percent and 60 percent will have abnormalities on a chest CT scan, though few of these irregularities will turn out to be cancer. The problem here is that patients are made to worry unnecessarily. "Cancer" is such a dreaded diagnosis in our culture—spoken of in whispers or referred to as "the C word"—that for most people, discovering that "it might be cancer" is no small thing, even if further testing is required.
Then there's the question of further testing, which, particularly for colon and lung cancer, can be fairly invasive. Lung biopsies, for example, may involve a needle passed through the chest wall or an actual open-chest surgery to remove sample tissue, depending on the location of the abnormality. Such procedures come with a host of possible complications, including infection, bleeding, partial lung collapse, pneumonia, and heart attacks, which necessarily give one pause. These problems may not occur very often—and accurate numbers are hard to come by—but former smokers, the people most likely to undergo testing, are also most likely to suffer complications since their hearts are generally weaker and their lungs don't heal as well or as quickly after biopsy.
A Risk of Overdiagnosis
Equally important, and perhaps more surprising, is the fact that some cancers will never progress to cause problems. That is to say, many more cancers are detected through screening than would ever turn out to be life-threatening or even uncomfortable for the patient (the buzzword here is "overdiagnosis"). This issue has been discussed largely for prostate cancer, in which tumors are generally slow-growing, and elderly patients sometimes die of other diseases (say, heart attacks) before their cancers cause significant symptoms. It's increasingly clear, however, that overdiagnosis occurs across the board, even in cancers long viewed as aggressive, such as lung cancer. As Dr. Barnett Kramer, associate director for disease prevention at the National Institutes of Health, said in a recent phone interview, the evidence that lung cancer, too, can be nonprogressive came as "an eye-opener"; "I would now say overdiagnosis is the rule, not the exception."
The evidence of this phenomenon is often indirect: If all of the newly discovered cases of prostate cancer, say, or of ductal carcinoma in situ, an early form of breast cancer, were destined to progress, our rates of prostate cancer mortality and of invasive breast cancer should be much higher than they are—even taking into account advances in treatment. The magnitude of overdiagnosis is difficult to pinpoint and varies from one type of cancer to another. But what's clear is that the more screening we do—and the more sensitive our technology—the more we will detect tiny cancers, many of which will be clinically insignificant.
The challenge here is to continually revise our understanding of what cancer is and how it evolves—or doesn't evolve—in the body. Not only do some abnormalities grow very slowly, some actually regress without treatment, as a result of complex interaction between precancerous cells and the body's immune system. This can be true, for example, of LSILs and HSILs, low-grade and high-grade squamous intraepithelial lesions, detected by Pap smears and linked to cervical cancer. As it turns out, through processes that are not well-understood, many—and some say most—LSILs and HSILs will simply improve on their own.
And yet another wrinkle arises from the ambiguity of some test samples: In more cases than you'd expect, pathologists disagree on whether a particular image shows cancer or not. In one especially telling study published in 1996 in Human Pathology, a panel of eight highly credentialed pathologists reviewed a series of 37 slides to determine which represented melanoma, or skin cancer, and which showed benign lesions. Surprisingly, for a significant minority of slides—38 percent of them—two or more pathologists disagreed with the majority opinion. This finding and others like it are important because they highlight the subjectivity associated with cancer diagnosis; subtle, cellular alterations may fall into a gray area between cancer and not-cancer, particularly for early stage cases—the very realm in which screening is routinely used.
A Risk of Overtreatment
Once an abnormality is labeled cancer, it is difficult for the patient and physician to "do nothing." In addition to subtle pressures on the doctor (the fear of malpractice, the prevailing standard of aggressive care), it is simply not possible to know whether a given, tiny lesion represents a case of overdiagnosis or a clinically significant finding. The inclination is usually to err on the side of caution and to proceed with treatment. But treatments can be harsh, ranging from surgery (in the case of women with DCIS) to radiation and chemotherapy, all of which have severe side effects and which no one would want to undertake unnecessarily.
The furor over mammography—triggered in part by a meta-analysis published in the Lancet in 2000—focused on the contention that screening did not reduce women's overall mortality; worse still, in one study, mortality for the screened women was actually slightly higher than for the control group, a finding attributed to overtreatment—in this case, increased heart attacks caused by radiation therapy. Radiation protocols have now been changed to minimize the heart region's exposure. But a fundamental question remains: Are there cases in which the cure is worse that the disease?
The answer is clearly yes—at least some of the time. In prostate cancer, abnormal cells are often slow-growing, and treatment can cause impotence and incontinence. Dr. Stephen Taplin, a senior scientist at the National Cancer Institute, helpfully compares some prostate cancers to gray hair, more a byproduct of aging than a life-threatening issue. "If I made men impotent and incontinent because they had gray hair, there wouldn't be any question I'd be hurting them," he said in a phone interview. But if these problems occurred as a result of aggressive cancer treatment, "most men would say, 'Doctor, you've saved me!'"
A final, terrible irony is that while screening leads to overdiagnosis and overtreatment, it also misses some cancers—and these tend to be the most aggressive, fastest-growing ones. This is because fast-growing abnormalities (for any type of cancer) are statistically more likely to develop during the window between tests, causing problems before, say, an annual screening can provide fair warning.
So how to explain the public's simple faith in testing—the significant gap between scientific evidence and popular perception? Many social and cultural pressures conspire here—and a complete catalog would no doubt include everything from physician report cards (which rate physicians according to the percentage of patients screened) to celebrity testimonials, from the financial interests of some doctors and health networks invested in imaging to the well-intentioned work of advocacy groups, particularly for women.
But one factor that has really muddied the debate deserves special mention: the "five-year survival rate," as it is called, often deployed to support screening. ("Five-year survival" represents the percentage of people diagnosed with a particular kind of cancer at a particular time who are still alive five years later.) As Dr. H. Gilbert Welch points out in his excellent book, Should I Be Tested for Cancer? this is a highly misleading statistic for the following reason: When cancers are detected early, the five-year survival rate (dated from the time of diagnosis) will necessarily improve—even if patients live no longer than they would have otherwise. Overdiagnosis further inflates the figure since more people are identified with nonprogressive cases who can be expected to live longer.
The public-health challenge, then, is to convey a more balanced, realistic message about cancer testing so that people will be receptive to negative as well as positive news about particular tests. There is good evidence to support regular Pap smears in women, no good evidence (at least not yet) to support routine lung-cancer screening for former smokers. Thus, it is particularly disheartening to see a large-scale screening program such as the New York Early Lung Cancer Action Program (full disclosure: NY-ELCAP is led by researchers at Cornell Medical School, where this writer studied medicine), which lacks a control group and so will not be able to clarify whether screening 10,000 former smokers actually saves lives. (A devastating critique of NY-ELCAP by Dr. Steven Woloshin, along with Schwartz and Welch, is available in the Lancet, but not for free.) That this massive project is heavily funded by New York's tobacco settlement fund provides a further, unfortunate twist.
Ultimately, the public needs to set aside automatic enthusiasm for screening and develop a new kind of savvy—one that balances hope with a certain dose of healthy skepticism and leads people to embark on testing only after considering a host of variables, both personal and scientific. As it turns out, in cancer screening, as in so much else, there really isn't a free lunch.
Amanda Schaffer is a science and medical columnist for Slate.
Illustration by Robert Neubecker.