In this analysis of US incidence trends during the last 20 years, we estimated that more than a million additional men have been diagnosed and treated for prostate cancer because of introduction of PSA screening. The increase in diagnosis and treatment associated with screening has been most dramatic among men younger than 50 years.
It is important to acknowledge that there can be two sides to screening—it may result in both a cancer-specific mortality reduction and an overdiagnosis. But even using the most optimistic assumption about benefit, the vast majority of these additional 1 million men did not benefit from early detection.
There are a number of methodological concerns that could be raised about our study. First, some might question the choice of 1986 as the base year. It is true that the first “clinical trial” indexed in MEDLINE examining PSA as a screening test did not appear until 1991 (20
), but we did not choose 1990 as the base year for several reasons. The report of the 1991 trial is actually cited less often than the 1987 article (21
). More importantly, choosing 1990 would miss an 18% incidence increase between 1989 and 1990—an increase undoubtedly related to the initiation of Prostate Cancer Awareness Week, which recruited asymptomatic men to have prostate screening examinations that used PSA testing (22
Second, others might raise the concern that the underlying (or “true”) incidence of prostate cancer is increasing and that it is incorrect to attribute the entire increase since 1986 to PSA screening. In fact, prostate cancer incidence was slowly increasing (approximately 2% per year) during the decade before 1986. Virtually, all of this increase, however, was explained by the growth of incidentally detected prostate cancers associated with the increased use of transurethral resection of the prostate before 1986 (23
). Transurethral resection of the prostate-detected cancers actually represented half of all prostate cancers diagnosed in 1986, but then fell off dramatically as the use of the procedure declined (ie, a 50% drop in the rate of transurethral resection of the prostate-detected cancer from 1986 to 1993) (20
). In other words, in the absence of PSA screening, prostate cancer incidence would have declined after 1986. Because we used 1986 as our base year and because 1986 represents the maximal effect of transurethral resection of the prostate on prostate cancer incidence, our estimates of the effect of PSA screening represent underestimates.
Third, the estimate of the number of additional men treated was based on the assumption that the treatment patterns observed in the general population are the same as for those who were additionally diagnosed. This estimate would be an overestimate if the men who were additionally diagnosed were less likely to receive treatment than those in the general population; it would be an underestimate if they were more likely to receive treatment. The latter seems more probable, given that the additionally diagnosed men must have been screened and that men who are screened are more likely to be healthy and, thus, more likely to undergo surgery or radiation.
Finally, many might point out that our assumptions about the effect of screening on prostate cancer mortality are grossly exaggerated. And they would be correct—it is inappropriate to assume that the entire decline in mortality is the direct result of advancing the time of treatment (early detection) and that none of it is because of advances in treatment itself. Some of the mortality decline is the result of treatment improvements, such as the early initiation of antiandrogen therapies, improved radiation protocols, or chemotherapy. Furthermore, the recent randomized trials of PSA screening have reported mixed effects of screening on mortality—the European finding was favorable (14
) and the Prostate, Lung, Colon, Ovary finding was unfavorable (13
). These results make it highly unlikely that PSA screening could have the mortality effect that we assumed in this analysis.
Estimating the trade-off between a mortality benefit and an overdiagnosis is problematic when there is uncertainty about whether the benefit exists at all. Our approximation of about one death averted to 20 men overdiagnosed was simply intended to provide an upper-bound estimate. A more plausible estimate would assume the mortality benefit observed in the European trial (14
) and its earlier reported estimate that 48% of patients diagnosed in the screened group had been overdiagnosed (25
). When we applied this estimate to the overall prostate cancer incidence in the screened group (82 per 1000 men), we obtained an overdiagnosis incidence of 39 per 1000. Given the European trial report that 1410 men need to be screened to avoid one death (25
), this translates into a trade-off of approximately one death averted to 50 men overdiagnosed with prostate cancer (
1410 × 39/1000). Because the true mortality benefit approaches zero, the estimate for the trade-off approaches 1 to infinity.
Although no single formula can determine the correct course of action when facing this trade-off, it is important that we begin to explicitly communicate to men who are considering screening the relative magnitude of number of deaths averted to the number overdiagnosed. And regardless of the estimate used—whether it is one death to 20 men being overdiagnosed, one to 50, or one to infinity—it is equally important to make clear the harms of overdiagnosis. The primary harm of overdiagnosis is unneeded treatment. Overdiagnosed patients cannot benefit from treatment because their disease is not destined to progress to cause symptoms or death. Prostate cancer treatment has known risks, including impotence, incontinence, and even death for surgery; and impotence, urgency, painful defecation, and radiation enteritis (26
) for radiation. All overdiagnosed patients are needlessly exposed to the hassle factors of obtaining treatment, the financial implications of the diagnosis, and the anxieties associated with becoming a cancer patient—consequences that, by our estimate, have occurred among more than a million American men since the initiation of PSA screening.