"While there was no further reduction of prostate cancer risk after finasteride was discontinued, there was also no evidence that stopping finasteride resulted in more cases of prostate cancer," writes Badar M. Mian, MD.
“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature. Dr. Mian is associate professor of surgery in the division of urology at Albany Medical College, Albany, NY.
The Prostate Cancer Prevention Trial (PCPT) was a placebo-controlled, double-blind randomized controlled trial showing that using the 5-alpha-reductase inhibitor finasteride (Proscar), 5 mg daily for 7 years, could reduce the risk of prostate cancer by 25%. The trial duration was limited to 7 years of treatment and follow-up due to the substantial cost and burden of randomized controlled trials. However, some questions had emerged, such as whether the trial duration was sufficient to demonstrate the maximum benefit of finasteride. Another concern was whether the reduced risk of prostate cancer would be maintained after discontinuation of finasteride at the end of the trial.
A recent report by Unger et al, using the innovative approach of linking the PCPT clinical data with Medicare claims, confirms that the beneficial effect of finasteride in reducing the risk of prostate cancer is maintained for up to 16 years (J Natl Cancer Inst 2018; 110:djy035).
Also by Dr. Mian: Large study challenges long-held views on Gleason 10 PCa
In order to determine the risk of prostate cancer beyond the 7-year study period, the authors linked the PCPT clinical records to the participants’ Medicare claims data using Social Security number and date of birth. This linkage allowed the diagnosed prostate cancer to be identified by both the clinical records and the Medicare claims.
Of the 18,880 PCPT participants (finasteride: 9,423; placebo: 9,457), 14,176 (75.1%) had a linkage to Medicare claims (finasteride: 7,069; placebo: 7,107). The time interval from randomization in the PCPT to the end of Medicare coverage for the men linked to the Medicare database was a median 16 years for both groups. The authors analyzed the prostate cancer risk over three follow-up periods: 0-6.5 years, 6.5-7.5 years (to account for the end-of-study biopsy-detected prostate cancer), and after 7.5 years (to assess the prostate cancer risk after the completion of the trial).
Over the entire follow-up period, the cumulative incidence of prostate cancer was 22.3% in the placebo arm and 18.1% in the finasteride arm. In the first 7.5 years, the finasteride arm had a 29.1% lower hazard ratio for prostate cancer diagnosis. However, after 7.5 years, the risk was stable and there was no statistical increase or decrease in the prostate cancer risk.
Next: 21.1% decrease in HR observed21.1% decrease in HR observed
During the entire follow-up, finasteride arm participants had a 21.1% decrease in the hazard ratio of prostate cancer. The hazard ratio for prostate cancer development remained in favor of finasteride during all the follow-up windows (0-6.5; 6.5-7.5; 7.5-16 years); ie, there was no decrease in the beneficial effect of finasteride over time, even after the trial had ended.
This interesting and novel use of secondary data sources can enhance our ability to detect long-term outcomes of clinical trials. The PCPT is especially suited for this linkage approach because the age for PCPT participation was 55 years and Medicare enrollees are 65 years of age or older. The use of Medicare claims data linked to clinical trials data to provide long-term follow-up of trial participants can help answer some of the questions mentioned above in a relatively low-risk manner, with minimal cost.
Finasteride use lowered the risk of prostate cancer both prior to and including the 7-year biopsy period (25.2% and 29.1%, respectively). While there was no further reduction of prostate cancer risk after finasteride was discontinued, there was also no evidence that stopping finasteride resulted in more cases of prostate cancer. This would confirm that finasteride prevented the development of prostate cancer and not simply delayed the diagnosis of prostate cancer.
A significant gap in knowledge and a limitation of this report is the lack of Gleason grade to distinguish high-grade cancers over time. While the initial results reported a higher incidence of high-grade prostate cancer in the finasteride group, this concern should have been alleviated by a number of subsequent reports showing no change in adverse outcomes or mortality. Further, Medicare claims for the use of oral medications such as finasteride were not available previously, so it’s possible that some men may have restarted finasteride.
It appears that the prostate cancer risk reduction by finasteride use for a limited number of years may continue over the long term (21.1% decreased risk for a median of 16 years). Hopefully, this and previous research confirming the long-term reduction in prostate cancer diagnosis will give urologists a strong reason to take a second look at the use of finasteride for prostate cancer prevention.