Neil Fleshner, lead researcher of the investigation from Princess Margaret Hospital, Toronto, Canada, said:
"Our trial is the first study to show the benefits of use of a 5α-reductase inhibitor to reduce the need for aggressive treatment in men undergoing active surveillance for low-risk prostate cancer...delaying their time to pathological progression and initiation of primary therapy."
In the United States about 20% of males will be diagnosed with the disease, although the majority will have low-risk (low-grade, low-volume) prostate cancer. For them, it can be appropriate to stay under conservatively managed active surveillance, meaning they do not have to undergo immediate therapy in favor of regular assessment and biopsies to monitor the disease.
Dutasteride is a 5α-reductase inhibitor that works by preventing testosterone from converting to dihydrotestosterone (the male sex hormone involved in the development of prostate cancer). The drug has been approved for treating benign prostatic hyperplasia, a non-cancerous enlargement of the prostate, and has shown to decrease the volume of some prostate cancers.
302 men aged between 48 to 82 years old undergoing active surveillance for low-risk localized prostate cancer were enrolled to participate in the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM). The researchers randomly assigned the participants to two groups; one group received 0.5 mg dutasteride once daily for 3 years, while the other group received placebo for the same duration.
In order to measure time to disease progression, participants received biopsies at 18 months and 3 years. In addition, the researchers gave participants a questionnaire in order to examine anxiety associated to the disease.
The researchers found that dutasteride considerably delayed disease progression in comparison with placebo - 48% of men given placebo experienced disease progression compared with 38% of participants receiving dutasteride.
Furthermore, cancer was less likely to be detected at final biopsy for participants in the dutasteride group (36% [50 men]) compared with 23% (31) men in the placebo group. Throughout the duration of the study, those who received dutasteride also reported considerably lower cancer-related anxiety compared with men in the placebo group.
Similar side effects were observed between both groups. Drug-related adverse effects, consisting mainly of adverse sexual events or breast enlargement or tenderness, were experienced by more participants in the dutasteride group (24%) than those given placebo (15%). There were no cases of disease spread or deaths related to prostate cancer during the duration of the study.
In an associated comment, Chris Parker from the Royal Marsden National Health Service Foundation Trust, Sutton, UK warns:
"These data are consistent with the hypothesis that dutasteride reduces the volume of low-grade prostate cancers but has no effect, or even an adverse effect, on the progression of high-grade disease. Thus, although reducing overall prostate cancer detection, dutasteride could plausibly have no effect (or possibly a deleterious one) on prostate cancer mortality."
The researchers conclude:
"The benefit of dutasteride is to reduce the amount of low-grade cancer, not to reduce the risk of being diagnosed with higher-grade cancer. This reduction leads to fewer men with biopsy-detectable prostate cancer, and therefore fewer treatment interventions. Dutasteride...provides a treatment option for men with low-risk, localized disease."
Written by Grace Rattue