What was the rationale for trying finasteride as a way to prevent prostate cancer?
Finasteride blocks the activity of an enzyme called 5-alpha reductase. This enzyme converts the hormone testosterone to dihydrotestosterone, which is the most potent androgen in the prostate.
What is interesting is that men born with a deficiency of the 5-alpha reductase enzyme, a rare genetic condition, have undetectable levels of prostate specific antigen (PSA) and do not develop prostate cancer. So it made sense that finasteride, already approved for the treatment of male pattern baldness and benign prostatic hyperplasia, could also reduce the risk of prostate cancer.
There was a 25% relative reduction in prostate cancer risk in PCPT. Did this large reduction surprise you?
The finding that finasteride reduced the 7-year prevalence of prostate cancer by 25% was actually in line with what we expected.
A more surprising finding was the unexpectedly high overall prevalence of prostate cancer, which was about 25% in men in the placebo group and around 18% in men receiving finasteride. This was due to two factors:
First, all the men in the study underwent annual PSA screening. And second, about a third of the study participants agreed to have a research biopsy at the end of the 7-year study despite having PSA results always below 4 ng / dl on their annual screening exams, limit above which prostate biopsies are usually recommended.
In fact, these end-of-study biopsies reflected nearly half of all prostate cancers diagnosed at PCPT. This observation, in particular, provides important information on the problem of overdiagnosis , which refers to the diagnosis of prostate cancer that is not destined to become clinically evident throughout a man’s life.
What about the finding of increased risk of high-grade cancer? Does the January 2019 Prostate Cancer-Specific Survival Study End Debate Over That Finding?
You are referring to the fact that despite nearly 20 years of follow-up, we did not see an increase in prostate cancer mortality among men who took finasteride.
Given the relatively small number of men who died of prostate cancer in both study groups, these findings probably won’t end the debate. But I think they help us a lot to clarify concerns about the possibility that this drug increases the risk of life-threatening prostate cancer.
So how do you explain the increased risk of high-grade cancer that was reported in 2003?
There are two mechanisms by which we think that finasteride improves the detection of high-grade cancer in prostate biopsies.
First, finasteride is known to decrease the size of the prostate gland by approximately 25%. When a smaller gland is biopsied, the sample is more likely to include an area of cancer (or high-grade cancer) with the biopsy needle, compared to the same biopsy performed on a larger gland.
Second, as we showed in another analysis of the PCPT, finasteride improves the sensitivity of the PSA test for the detection of general and high-grade prostate cancer. Because the decision to perform prostate biopsies during the study was based on PSA concentrations, it may have contributed to increased detection of prostate cancer in general, and high-grade prostate cancer in particular, among patients. men who received finasteride.
If we consider the effects of this drug on gland size and PSA performance, it seems quite likely that PCPT not only overestimated finasteride damage in terms of the observed increase in high-grade cancer, but also underestimated the benefit of finasteride in terms of relevance in reducing the risk of prostate cancer.
In the future, is there a place for finasteride in the context of prostate cancer prevention?
Although finasteride is not approved by the FDA for the prevention of prostate cancer, it is approved for the treatment of urinary symptoms caused by benign prostatic hyperplasia. And while benign prostatic hyperplasia does not appear to be a risk factor for prostate cancer, finasteride is a reasonable option for its treatment because it may lower a man’s risk of developing prostate cancer while improving prostate cancer. urinary symptoms from benign prostatic hyperplasia.
Importantly, finasteride can have side effects, including sexual side effects. In PCPT we noticed a small but statistically significant increase in these side effects. There were also reports of an increased incidence of depression associated with finasteride. Therefore, both the possible risks and benefits of finasteride should be informed in the discussion about its use.