None of the trials conducted to date have provided sound information as to the risk and benefits associated with PSA testing among younger men (aged, say, between 35 and 50 years of age) who have well-known risk factors for prostate cancer. Such risk factors, of course, include:
- A meaningful family history of prostate cancer
- African American race, or other forms of Black African ethnicity (e.g., Afro-Caribbean and, potentially, Afro-European)
- A history of exposure to certain types of environmental risk (e.g., Agent Orange)
In a new paper in the Journal of Urology, Vertosick et al. set out to see if they could offer insight into two questions:
- “Do race and family history increase risk sufficiently to justify differential screening?”
- “Might there be other risk factors that lead to superior risk stratification?” (compared to race and family history).
We should be clear that this is a complex paper involving a significant number of estimates and assumptions. It is not a prospective analysis of data from a large clinical trial; it is a theoretical and hypothesis-generating analysis based on extant data. It therefore has to be read with care and interpreted with caution. However, having said that, here is a summary of what Vertosick and her colleagues argue that they have been able to demonstrate from the data that are available:
- Screening based on family history as a risk criterion involves about 10 percent of men and accounts for about 10 percent of prostate cancer-specific deaths.
- Screening based on Black race as a risk criterion involves about 13 percent of men and accounts for about 28 percent of prostate cancer-specific deaths.
- 44 percent of prostate cancer-specific deaths occur in the 10 percent of men who have the highest PSA levels at age 45 years.
- Under no identifiable scenario that assessed risk for prostate cancer-specific mortality based on family history or Black race did the ratio of the risk group size to the number of prostate cancer-specific deaths in that risk group approach that of PSA level.
Given the fact that we have no evidence that either race or family history have any impact on the relationship between PSA level and risk for prostate cancer-specific mortality, Vertosick and her colleagues draw three core conclusions from their data:
- PSA levels at age 45 offered the best risk-related ratio between men screened and potential prostate cancer-specific deaths avoided.
- PSA-based risk stratification would probably include men of Black race and men with a family history of prostate cancer who are at significant risk for aggressive forms of prostate cancer themselves.
- Differential screening based on risk should be informed by a baseline PSA level.
The term “informed by” immediately above has been deliberately emphasized by us and not by the authors.
The key point that the authors are trying to make is that if early testing of high-risk subsets of patients is to be recommended by guideline-writing groups such as the American Urological Association or the National Comprehensive Cancer Network (and other guideline writing groups around the world), then baseline PSA testing should be a key factor in how those patients are being assessed. We would note that Vertosick and her colleagues neither recommend nor do they argue against the value of early testing of high-risk patients.
In an editorial comment on this paper, Hoffman implicitly commends Verstosick et al. for not recommending baseline PSA testing in all men before the age of 50 years. However, the authors responded to that editorial comment by observing that:
There are no good reasons to believe that screening a man at age 45 years would result in greater harms or fewer benefits than screening a man at age 50 years. Rather, it is likely that the opposite is true since the risk of over diagnosis is low in a man with an anticipated life expectancy of greater than 30 years.
In the opinion of The “New” Prostate Cancer InfoLink, the realities of the value of PSA testing are, to a very large extent, still being masked by the behaviors of doctors and patients (as opposed to the actual risks). If an elevated PSA level of > 0.7 ng/ml led only to careful monitoring of that patient over time until a biopsy was actually justifiable, and if active surveillance was the actual standard of care until treatment was actually necessary, then it would become a great deal easier to appreciate and act on the concept of a baseline PSA level for most men at age 45 or thereabouts. The problem, of course, is that any elevated PSA level still tends to lead to a biopsy and any amount of cancer being found in the prostate still tends to lead to early, if not immediate, treatment. Until we can resolve that problem, we need to continue to be cautious about the over-use of baseline PSA testing in men who are under (say) 50 years of age.
As Hoffman writes in his editorial comment,
… clinicians should inform younger men at high risk about the uncertain value of early screening.
His statement is accurate. Young men at high risk who want to get a baseline PSA test need to appreciate that such a test is not definitive of anything. Although 44 percent of prostate cancer-specific deaths occur in the 10 percent of men who have the highest PSA levels at age 45 years, this also means that 56 percent of men who go on to die of prostate cancer do not have a PSA level in the top decile at age 45.
There are no easy answers … which is why Verstosick et al. are so careful to say only that “Differential screening based on risk should be informed by” (as opposed to defined by) a baseline PSA level.