A retrospective study has just been published that shows that the risk of experiencing a biochemical recurrence (PSA recurrence) after radical prostatectomy to treat prostate cancer increased significantly in men who received alpha blockers for lower urinary tract symptoms (LUTS) after surgery.
When compared to men who did not receive alpha blockers, those who did had a 72% increase in the hazard for a PSA relapse. Additionally, it also found that men treated with 5 alpha-reductase inhibitors (5-ARI) had a tendency toward an increased risk, however the difference did not achieve statistical significance.
But the real important fact is that the use of either drug after prostatectomy did not affect mortality according to researcher Teemu J. Murtola, MD, PhD. Dr. Murtola shared these findings at the recent American Association for Cancer Research’s (AACR) Frontiers in Cancer Prevention Research meeting.
Facts to remember when reading these results:
• The study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• The use of finasteride or dutasteride (5-ARI) was not associated with a statistically significant increased risk of biochemical relapse or prostate cancer mortality after radical prostatectomy.
Murtola said that “There is no clear biological reason why alpha blockers would increase the risk of biochemical recurrence. I think it is more likely that men who have urinary symptoms after radical prostatectomy represent a group at increased risk for biochemical recurrence. They just happened to be treated with alpha blockers.”
Clinical trials have shown that chemo-prevention with a 5-ARI reduces the risk of prostate cancer, although the FDA has not accepted this as fact. Data from the Prostate Cancer Prevention Trial showed an increased incidence of high-grade prostate cancer in men treated with finasteride, however many clinicians believe that this finding is an artifact of having the gland shrunk by the drug.
Since the impact of 5-ARI or alpha-blocker therapy on clinical outcomes after radical prostatectomy has not been previously examined, Murtola and colleagues performed a retrospective analysis of data for men who received one of the drugs following prostatectomy.
Their study included a sample of 1,315 men who had undergone radical prostatectomy for localized prostate cancer during 1995 to 2009. The men were followed at six-month intervals for the first year after surgery and then yearly thereafter.
Serum PSA was measured at each visit, and investigators defined biochemical failure as a rise in PSA from an undetectable to a detectable level after surgery.
Cause of death was determined by information from a national cancer registry, and medication use was ascertained by means of a national prescription database.
The cohort included 117 men who received a 5-ARI before surgery — finasteride (Proscar) or dutasteride (Avodart) — and 372 men treated with an alpha blocker before and/or after surgery.
Pathologic T stage and Gleason score did not differ among the 5-ARI, alpha-blocker, and control groups. However, men treated with a 5-ARI or alpha blocker had higher rates of lymph-node involvement and positive surgical margins.
Age, PSA level at diagnosis, Gleason grade, T stage, and margin status were independent predictors of biochemical relapse. Age and T stage were the only predictors of mortality.
Murtola reported that 424 men had biochemical relapse during a median follow-up of 3.17 years, and 124 died during a median follow-up 5.08 years, including 22 men who died of prostate cancer.
As compared with men who used neither drug, 5-ARI treatment was associated with a nonsignificant 1.38 hazard ratio for biochemical recurrence (95% CI 0.86-2.19).
Alpha blocker use was associated with a significantly higher risk of biochemical relapse compared with the control group (HR 1.71, 95% CI 1.31-2.25).
Among men treated with an alpha blocker, the timing of therapy influenced the risk of biochemical recurrence. Only those men who received a drug after surgery had a significantly increased risk compared with the control group.
Treatment with a 5-ARI or an alpha blocker did not influence overall mortality.
American Association for Cancer Research – Frontiers in Cancer Prevention Research; Murtola, TJ et al “Risk of biochemical recurrence after radical prostatectomy among men using 5-alpha reductase inhibitors and alpha-blockers” AACR-FCPR 2011; Abstract A97.
Joel T Nowak, M.A., M.S.W.