Men on active surveillance for low-risk prostate cancer (PCa) who take 5α-reductase inhibitors (5-ARIs) have a more favorable prognosis than men not taking the drugs, according to a new study.
In this study, PCa patients on active surveillance treated with 5-ARIs were approximately half as likely to experience pathologic progression or switch to active treatment compared with men not taking the medications, investigators reported online in European Urology. “This is particularly relevant in the current era in which we are cognizant of overdetection and overtreatment of low-risk prostate cancer,” the authors concluded.
The findings are based on a retrospective investigation by Antonio Finelli, MD, of Princess Margaret Hospital in Toronto, and colleagues. The study included 288 men on active surveillance for low-risk PCa, defined as a PSA level below 10 ng/mL, clinical stage T1c-T2a, Gleason score less than 6, and three or fewer cores positive, with no more than 50% of a core involved at initial diagnostic biopsy. Of the 288 subjects, 70 received 5-ARIs and 218 did not. The researchers excluded from the study men who were treated with 5-ARIs prior to being diagnosed with PCa. All subjects had a minimum of one repeat biopsy following their diagnosis.
After a median follow-up of 38.5 months, 93 patients (32%) experienced pathologic progression and 96 men (33%) abandoned active surveillance. The rate of pathologic progression was significantly lower in patients receiving 5-ARIs than in those not treated with the medications (18.6% vs. 36.7%). They also were more likely to discontinue active surveillance (20% vs. 37.6%).
Dr. Finelli and his colleagues defined pathologic progression as increased grade, increased number of cores to more than three or any core involvement greater than 50%.
After adjusting for multiple variables, the absence of 5-ARI treatment was associated with a nearly threefold increased likelihood of pathologic progression. This likelihood increased by 4% with each one-year increment in age.
The researchers acknowledged study limitations, which included the retrospective design and variable duration of 5-ARI therapy among study subjects. The study also was nonrandomized.
Previous studies have shown that men without PCa who receive 5-ARIs (i.e., finasteride or dutasteride) have an approximately 25% lower risk of PCa development.
A randomized, controlled study—the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial—is evaluating whether dutasteride decreases time to PCa progression. The trial will include 300 candidates for expectant management of biopsy-proven, low-risk localized PCa. Subjects will receive dutasteride 0.5 mg/day or placebo for three years.
“Upcoming level I evidence from the REDEEM study will establish whether there is a clinically-impactful role for 5-ARIs in active surveillance”, commented Lionel L. Bañez, MD, Assistant Professor of Urologic Surgery at Duke University Medical Center in Durham, N.C. “Until then”, he added, ”the fact that the current article [by Dr. Finelli and colleagues] suggests that some benefit may be derived from these pharmacologic agents among active surveillance patients, even when they were prescribed for non-prostate cancer indications, is quite encouraging.”
“Indeed,” continued Dr. Bañez, who is Database Director for the Duke Prostate Center, “if validated in a prospective manner, these findings would bring to light that 5-ARIs not only prevent prostate cancer, but could also prevent low-risk prostate cancer progression.”