The study addresses concerns that prophylaxis (preventive use) with finasteride would raise men’s probability of having a more aggressive cancer and reduce their chances of survival.
“Finasteride is safe, inexpensive, and effective as a preventive strategy for prostate cancer,” Ian Thompson, Jr, MD, principal investigator of the PCPT for SWOG, said in a press release.
PCPT, a large clinical trial testing the drug’s effectiveness as preventive in prostate cancer, indicated the treatment delayed or prevented the appearance of the cancer by 23%; however, it increased men’s chances of having a more aggressive cancer.
In this recent analysis, team members who led the study explained their conclusions in a letter to the editor, “Long-Term Effects of Finasteride on Prostate Cancer Mortality,” published in the journal New England Journal of Medicine.
A previous analysis of the Prostate Cancer Prevention Trial (PCPT) results — a seven-year study looking at the effect of finasteride in preventing prostate cancer — concluded the drug could prevent or delay prostate cancer.
Finasteride (sold under the brand names Proscar and Propecia) is a generic agent used to treat hair loss in males and benign enlargement of the prostate, namely to prevent urinary tract symptoms and complications.
Chemically speaking, finasteride is an inhibitor of 5α-reductase, which blocks the conversion of testosterone to dihydrotestosterone, a primary male sex hormone that can stimulate prostate cancer cells to grow.
The PCPT study was a placebo-controlled, randomized trial that enrolled a large sample of male participants (18,882), recruited from sites in the U.S. and Canada. Its goal was to determine whether prophylaxis with finasteride could reduce the prevalence of prostate cancer among initially healthy men age 55 and older during a seven-year period.
Indeed, a 24.8% reduction in the relative risk of prostate cancer was observed with finasteride. However, the study stopped 15 months earlier, as men treated with the drug developed aggressive tumors more frequently, specifically high-grade prostate cancer, scored 7 to 10 in Gleason score.
This finding led to recommendations against the use of finasteride for preventing prostate cancer.
Consistent with this former observation, a more recent study also suggests that men who take finasteride before being diagnosed with prostate cancer, tend to develop more advanced disease and later have higher mortality rates related to cancer.
However, subsequent studies suggested that the reason finasteride increases the likelihood of a high-grade prostate cancer diagnosis is because it improves the sensitivity of screening and diagnostic tests, including the PSA blood test, digital rectal exam, and prostate biopsy.
Despite those findings, the question remains whether the higher number of high-grade cancer associated with finasteride, increases — or not — the mortality due to prostate cancer.
To answer this question, the same team that led the PCPT, working at Fred Hutchinson Cancer Research Center and CHRISTUS Santa Rosa Hospital Medical Center, reviewed the death records of the trial’s participants, registered up to 2014. The frequency of deaths from prostate cancer over time was calculated, using as a comparator the risk of death due to other cases.
With a median follow-up of 18.4 years, 3,048 of the 9,423 men randomly assigned to take finasteride had died, including 42 due to prostate cancer. By comparison, from the 9,457 men randomized to placebo, there were 2,979 deaths, 56 caused by prostate cancer.
The results represent a 25% lower risk of death from prostate cancer under finasteride. However, this difference was not statistically significant due to the low number of casualties available for analysis, researchers said.
It is likely that the number of PSA-positive prostate cancer cases will increase given the recent recommendations to begin screening earlier, in men age 55 to 65. A timely diagnosis may reduce the risk of death, but also will increase the detection of cancers that could remain asymptomatic during a man’s lifetime.
The risk is that indolent cancers are unnecessarily managed with watchful waiting, implying frequent exams or biopsies, or treated with surgery or radiation, which may raise complications like impotence and incontinence and create anxiety.
“There are significant negative consequences to patients’ health and quality of life that can result from prostate cancer treatment, as well as to their finances and their peace of mind,” Thompson said. “If we can save people from surgeries, and scores of examinations and tests, and spare them from living for years with fear, we should. The best-case scenario for patients is prevention, and this trial has found an inexpensive medication that gets us there.”
Finasteride is a generic agent that “prevents prostate cancer,” researchers wrote. “The early concerns regarding an association between finasteride and an increased risk of high-grade prostate cancer have not been borne out,” they concluded.