he best-known downside of cancer screening, such as PSA tests for prostate cancer and mammograms for breast cancer, is that they often flag cancers that pose no risk, leading to overdiagnosis and unnecessary, even harmful, treatment. But widespread screening for “scrutiny-dependent” cancers — those for which the harder you look the more you find, and the more of what you find is harmless — causes another problem, two leading cancer experts argue in a paper published on Monday: increasing the apparent incidence of some cancers. That in turn is misleading doctors and the public about what increases people’s risk of developing cancers — or at least the types of cancer that matter.
“Detecting cancers that would never become apparent is screwing up our understanding of risk factors,” said Dr. H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice, co-author of the analysis in Annals of Internal Medicine.
The problem is especially clear in prostate, breast, and thyroid cancers, all of which are scrutiny dependent.
Men whose relatives developed prostate cancer are more likely to get PSA and other screening tests, either because they request them or because their physicians, noting their family histories, order them. Men with no such family history are less likely to be screened. Some men who get screened for prostate cancer and who are found to have elevated PSA levels undergo a prostate biopsy; some of those biopsies find cancer. (More than half of such cancers are so slow-growing that they don’t affect health or longevity.) Men who don’t get screened are less likely to have biopsies and so are less likely to be diagnosed with prostate cancer — not because they develop the disease at a lower rate but because they get screened at a lower rate. What you don’t look for, you don’t find.
“If we biopsied men without a family history of prostate cancer at the same rate that we biopsy men with a family history, we’d find more prostate cancer in them as well,” Welch said. “Family history influences how hard we look for prostate cancer and therefore how much we find. The risk factor becomes a self-fulfilling prophecy.”
A 2016 study of increased prostate cancer screening in men with a family history of the disease concluded that the risk due to family history has been overestimated by nearly half. “The risk factor of family history is spuriously strengthened because men with a family history are exposed to greater scrutiny,” write Welch and Dr. Otis Brawley, chief medical officer of the American Cancer Society, in the Annals report.
“There is a flaw in this logic” of identifying risk factors “on the basis of how many cancers we find,” agreed Dr. Peter Albertsen of UConn Health, an expert in prostate cancer.
In breast cancer, women who live in neighborhoods with the highest 20 percent of education and income are twice as likely to be diagnosed with that disease, a 2017 study found. That seemed to confirm reports of breast-cancer hot spots in some of America’s wealthiest areas, leading the government and others to spend tens of millions of dollars to find out why. Those studies came up empty: they found no association between rates of breast cancer and proximity to a hazardous waste site or pesticide exposure, for instance.
Wealthier, better educated women are, however, more connected to the health care system and therefore get more mammograms, breast ultrasounds, and MRIs. The more scrutiny, the more likely that harmless cases of breast cancer are found. (The idea of “harmless” breast cancer sounds like an oxymoron, but an estimated one-half of breast cancers detected by screening would never cause problems even if undetected and untreated.)
Breast tumors found by imaging are much more likely to be harmless than those discovered by women or their physicians finding a breast lump. Income and education are therefore less likely to be a true risk factor for breast cancer and more likely to be a “risk factor” for undergoing screening. If poorer, less educated women were screened for breast cancer at the same rate as wealthier, better educated women, the socioeconomic risk factor would likely vanish.
Thyroid cancers are also scrutiny dependent, which is why when countries launch screening programs the incidence of the disease skyrockets (but death rates don’t, showing that what’s being found is a false epidemic). In the U.S., women are about three times more likely than men to be diagnosed with thyroid cancer.
But the two sexes die of the disease at almost identical rates. Just as with prostate and breast cancer, that suggests we’ve been misled about the true factors that cause thyroid cancer, Welch and Brawley argue: women, who see doctors more than men, are more likely to be checked for thyroid cancer, more likely to have nodules detected and evaluated, and more likely to be diagnosed with small, indolent thyroid cancer. If men were screened as effectively for thyroid cancer at the same rate as women, sex as a risk factor for this cancer would likely disappear.
“They make good points,” said epidemiologist Noel Weiss of the University of Washington and the Fred Hutchinson Cancer Research Center. “There are circumstances where the rate of screening makes a difference” in how many cancers are detected and therefore in what seems to be a risk factor, “especially in thyroid and prostate cancer, where there is a large burden of hidden [harmless] disease.”
Welch and Brawley call for less focus on risk factors for developing cancers, since those numbers both determine and reflect who gets screened, and more on risk factors for death from cancer. “Death from disease or incidence of metastatic disease is probably more accurate and appropriate,” agreed UConn’s Albertsen, since both are “hard outcomes” not subject to what people choose to do.