Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS.
Materials/subjects and methods
The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995–2016). Pathologic, grade, and volume progression were the primary end points. Kaplan–Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time.
The cohort included 288 men with median follow-up of 82 months (interquartile range: 37–120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65–4.24), grade progression (HR: 2.75; CI: 1.49–5.06), and volume progression (HR: 3.15; CI: 1.78–5.56). The frequency of progression to high-grade (Grade Group 4–5) tumors was not significantly different between the groups.
Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4–5 disease.
With active surveillance, a doctor closely monitors a patient’s condition without giving any treatment unless the symptoms get worse. It is used for, among others, prostate cancer patients in whom the tumour is very small and contained within the prostate. Active surveillance may be stopped for these patients for instance when they start experiencing urinary problems. Urinary problems may occur when the enlarged prostate squeezes the urethra. Drugs out of the specific drug class called “5-alpha reductase inhibitor” may reduce these urinary problems by decreasing the size of the prostate. However, previous studies indicated that there may be a connection between this drug class and the development of advanced prostate cancer.
In this Canadian study, 288 men with prostate cancer were followed for almost seven years. The study reports that progression of prostate cancer was seen less often in men who used drugs out of the drug class “5-alpha reductase inhibitor.” No connection with advanced prostate cancer was found. As a result, drugs out of this drug class may be used during active surveillance, but it should be kept in mind that these drugs can have sexual side effects.