Dutasteride may decrease the incidence of lower grade prostate cancer, the REDUCE study has shown.

This double-blind, placebo controlled study enrolled men with elevated PSA levels. Entry criteria were baseline PSA 2.5-10 for men younger than 60, or 3.0-10 for older men, with a negative prostate biopsy in the six months prior to enrollment. A total of 8,231 men aged 50 to 75 were randomised to either dutasteride or placebo and followed up for four years. Participants received prostate biopsies as part of the protocol or because of a rise in PSA levels.

The primary end point for the study was biopsy-detectable cases of prostate cancer. Overall during the four years of the study, 858 out of 3,424 patients (25.1%) developed prostate cancer in the placebo arm versus 659 out of 3,305 patients (19.9%) in the dutasteride group, representing a 5.1% absolute risk reduction. This gives a number needed to treat of approximately 20 over four years and a 23% relative risk reduction.

However, the results of this study need to be interpreted with caution, as this headline reduction in cases of prostate cancer does not tell the whole story.

First, the decrease in prostate cancer was limited to low-grade (Gleason 5 and 6) tumours, with no statistical difference seen in higher grade (more aggressive) tumours.

The latter are more likely to be clinically significant or lethal to the patient. However, this finding cannot be completely dismissed given the number of men receiving radical treatment for low-grade prostate cancer at the present time.

Second, it must be remembered that the vast majority of tumours diagnosed during this study were picked up by protocol-driven biopsies and not by clinical need as would be the case in normal practice. Of the biopsies performed in the study because of clinical indication, the incidence of prostate cancer was 16.6% in the dutasteride group versus 16.7% in the placebo arm.

While the role of 5 alpha-reductase inhibitors in controlling male lower urinary tract symptoms is increasingly clearly defined, there has for many years been a theory that these drugs may also have an effect in preventing cases of prostate cancer. This was first studied using finasteride in the Prostate Cancer Prevention Trial (PCPT) which although it showed an overall reduction in prostate cancer events also found a concerning small increase in more high-grade aggressive tumours (possibly due to an artefact caused by the study design).

REDUCE is an important study, but it must be interpreted with caution. While it shows interesting results in terms of overall reduction of prostate cancer cases, the story is complex and there is clearly more work to be done in establishing the exact role of 5 alpha-reductase inhibitors in reducing the risk of prostate cancer.

Dr Jonathan Rees