5-ARI efficacious regardless of BPH symptom severity

December 1, 2010

In men treated with dutasteride (Avodart) for prostate cancer, the frequency of acute urinary retention, prostate surgery, and BPH symptoms decreases irrespective of prostate volume or symptom severity.

Treatment with the 5-alpha-reductase inhibitor was associated with as much as an 81% reduction in the incidence of AUR/BPH-related surgery compared with placebo.

Analysis of response by symptom severity and prostate volume showed that dutasteride treatment significantly reduced BPH symptom scores across the entire spectrum of baseline symptoms and volumes, except for a nonsignificant reduction in men who had both small prostates and mild symptoms, as reported at the AUA annual meeting in San Francisco.

The findings came from an analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. The principal objective of the trial was to evaluate chemopreventive potential of dutasteride in high-risk men. The primary results showed a 23% reduction in the relative risk of prostate cancer among men treated for 4 years with dutasteride compared with placebo.

Dr. Roehrborn reported the findings of a secondary analysis that compared the effects of dutasteride and placebo on BPH-related outcomes across a range of symptom scores and prostate volumes. The analysis involved 7,824 men ages 50 to 75 years, who had PSA values between 2.0 and 10.0 ng/mL, prostate volume <80 cc, and an International Prostate Symptom Score (IPSS) <25.

The primary outcomes of the BPH analysis were change in IPSS and time to AUR or BPH-related surgery. The outcomes were assessed in four patient subgroups: IPSS <8 and prostate volume <30 cc; IPSS <8, volume ≥30 cc; IPSS ≥8, volume <30 cc; and IPSS ≥8, volume ≥30 cc.

Separation of the patients into the subgroups showed that 48.2% of the REDUCE population had moderate to severe BPH symptoms (IPSS ≥8) and a large prostate volume (≥30 cc), and 33.4% of the study participants had mild BPH symptoms (IPSS <8) and large prostate volumes. The remaining patients had smaller prostates and either moderate to severe BPH symptoms (8.8%) or mild symptoms (9.6%).

At the end of the study, the reduction in IPSS was significantly lower (p<.001) with dutasteride in every subgroup except men who had mild symptoms and small prostates, and that subgroup exhibited a trend in favor of dutasteride. The magnitude of the difference ranged from 0.54 to 2.46 points on the IPSS.

The same pattern emerged from the analysis of AUR/BPH surgery. Dutasteride was associated with significant reductions (p<.001) in all groups except men who had small prostates and mild BPH symptoms. The reduction in relative risk ranged from 48% to 81%. All three statistically significant differences exceeded 70%.

Dr. Roehrborn and his co-authors have a financial and/or other relationship with GlaxoSmithKline, which sponsored the REDUCE trial.