Former President Joe Biden’s diagnosis of metastatic prostate cancer may cause a lot of frightened seniors (>70) to react inappropriately. Some may ask their doctors for a PSA (prostate specific antigen) test despite the US Preventive Services Task Force’s recommendation not to screen for prostate cancer in men older than 70.
The problem with PSA screening has never been adequately explained to the public. Prostate cancer comes in two forms, which may be two different diseases – limited and lethal. The former is typically without symptoms and is unlikely to cause mortality. The latter, as its name indicates, is the cause of virtually all deaths from prostate cancer. The problem is that the PSA doesn’t distinguish between the two – it’s elevated in both.
The High Prevalence of Undiagnosed Prostate Cancer at Autopsy: Implications for Epidemiology and Treatment of Prostate Cancer in the Prostate-Specific Antigen-Era is a study from Harvard Medical School that examines the prevalence of prostate cancer in men who had no manifestations of the disease and who died of other disorders. The study can be downloaded below.
The study found a very high prevalence of prostate cancer in men without any manifestation of the disease. The data are in the figure below. The prevalence is so high that if this indolent prostate cancer progressed to a lethal form, death from prostate cancer should be orders of magnitude higher than it is.
The authors state: “The high prevalence of asymptomatic and unsuspected prostate cancer, as demonstrated by these autopsy and biopsy studies, underlies the potential for widespread diagnosis of cases of prostate cancer that would have caused no clinical harm had they remained undetected. The overdetection of prostate cancer has obvious adverse clinical consequences, since many treated men experience no direct clinical benefit from treatment. It has been estimated that 42-66% of diagnosed prostate cancers would have caused no clinical harm had they remained undetected…
“Autopsy studies confirm a high prevalence of asymptomatic and undiagnosed prostate cancers in men as young as 30 years of age, and the prevalence increases with age such that about half of Caucasian men over 80 years likely have indolent prostate cancer.”
“[The data] suggest distinct etiologies between indolent and lethal prostate cancers. Until better surrogates are identified and validated, population and prevention research should focus on risk of potentially lethal prostate cancer as the primary outcome.”
The problem of not distinguishing between the indolent and lethal forms of prostate cancer is that many men will have prostate biopsies and treatment that carries significant morbidity for a disease that may never cause them any harm. Examine the figure below. Many, if not all, lethal prostate cancers may be so aggressive that they metastasize so rapidly that screening can’t keep up with them. They would be Tumor D in the illustration. Many of the indolent or non-lethal cancers correspond to Tumors A and B.
Another possibility that deserves consideration is the progression of non-lethal prostate cancer to an aggressive form. If they are two distinct diseases, then the “progression” may be the occurrence of a second disease rather than the evolution of a mild disorder to a fatal one. This hypothesis is speculative, but it must be disproved before it’s discarded.
The authors of the study described in this post are epidemiologists. A lifetime of observation of the interaction between oncologists and epidemiologists has convinced me that the former consider the latter to be harbingers of nihilism and consequently do all they can to ignore their nay saying. Regardless, routine PSA testing will remain a dilemma for both patients and primary care physicians until we devise better tests to separate the indolent from the lethal prostate cancers, such that mortality from the latter is decreased.
