In the mid19th century, a german pathologist named Rudolf Virchow discovered that leukemia was caused by the rapid multiplication of abnormal white blood cells. Just like that, with some autopsy samples and a light microscope, Virchow defined cancer a process in which healthy cells mutate and then reproduce. Before this revelation and for many decades after it, cancerous tumors were found and cut out only when they became visible or palpable. But Virchow's notion that cancer cells start out normal and then go rogue laid a foundation for modern medicine's approach to the disease: early detection.
These days, we no longer have to wait for tumors to make themselves evident. We don't even have to wait for symptoms. Now doctors look for abnormal cells in healthy people, hoping to catch and remove them before they cause sickness, a strategy that has had remarkable results. Along with treatment advances, mammography has reduced the U.S. breast-cancer mortality rate by some 30% since 1989. Pap smears have helped lower the cervical-cancer mortality rate by 60% since 1975. The rate of death from colorectal cancer is also steadily dropping, thanks largely to screening.
It seems that we should be better off finding all cancer early. But this logic may be flawed. Virchow never imagined that modern medicine would have the tools to find tiny cancers at such early stages. The field now includes highly sophisticated blood tests, ultrasound, computed tomography (CT), X-ray, magnetic resonance imaging (MRI) and fine-needle biopsy. Paradoxically, we've become so adept at finding abnormal cells early that there are more cancer patients than ever before. About 4% of the U.S. population are "cancer survivors." "If we had a 100% sensitive test that could pick up everything a pathologist would call cancer, it's conceivable that most of us, if not all of us, would be found to have cancer," says Dr. Barnett Kramer, a medical oncologist and former associate director for disease prevention for the National Institutes of Health (NIH).
"One of the problems is what our definition of cancer is," says Dr. Otis Brawley, chief medical officer of the American Cancer Society (ACS). "Through all the iterations in science, all the advancements in imaging, in understanding diagnostics, in understanding how to do biopsies, we still use Virchow's definition of cancer."
Happily, we don't also use his definition of how the disease progresses. Virchow believed all cancers would eventually spread and lead to death. Yet as scientists have learned how to detect and treat cancer earlier, they have also learned that some cancers never cause any sickness at all. In rare cases, certain cancers can even disappear without treatment. "Early diagnosis has changed the face of what it means to have cancer," says Dr. H. Gilbert Welch, a clinical epidemiologist, cancer-screening researcher and internist at the Veterans Administration Medical Center in White River Junction, Vt. The problem, he says, is that "there are really bad cancers and there are really innocuous ones that never go anywhere, and we're not good at sorting them out."
So we continue to look for more cancers early and treat nearly everything we find as though it would be fatal not to. Patients don't complain. Why would they? Even though the U.S. has so many effective treatment options available the best in the world, in fact cancer kills some 600,000 Americans every year. Countermeasures like screening that can be administered in a controlled manner seem like antidotes not only to cancer but also to the disease's inherent unpredictability.
But looking for signs of illness in seemingly healthy people is complicated. Cancer screening is truly effective only if the growths found would eventually cause sickness and if finding those growths earlier increases the efficacy of treatment. Absent these two conditions, finding cancer via screening is what's known as "overdiagnosis," which is guaranteed to happen when screening is performed population-wide. Overdiagnosis causes harm ranging from unnecessary worry to death in rare instances. Says Welch, a professor at Dartmouth Medical School and the lead author of a new book titled Overdiagnosed: "Theoretically, we could spend every day looking for early signs of disease. And we're getting closer and closer to that."
Do No Harm, Unless ...
even in cases in which cancer screening has clearly saved lives, its precise use is controversial. With breast cancer, a debate rages over when women with no risk factors should begin mammography. In 2009 the U.S. Preventive Services Task Force (USPSTF), an independent government body, advised that women get routine mammograms every other year beginning at age 50. Previously, the group had said that mammograms should be annual and begin at 40, which the ACS and other advocacy groups still say is best. The USPSTF changed its advice after determining that the collateral damage of annual screening beginning at 40 wasn't worth the payoff.