Dutasteride reduced the risk of prostate cancer in men at high risk for the malignancy who participated in an international randomized clinical trial.
During the 4-year study involving more than 6,700 men, about 20% of those taking dutasteride were found to have prostate cancer on random biopsies, compared with 25% of those taking placebo. This reduction was seen chiefly in tumors with Gleason scores of 5–6; the number of higher-grade tumors did not differ significantly between the two groups, said Dr. Gerald L. Andriole of Washington University, St. Louis, and his associates.
In an editorial, Dr. Patrick C. Walsh of the James Buchanan Brady Urological Institute, Baltimore, argued that real-world patients have biopsies only when indicated by the findings on prostate-specific antigen testing or digital rectal exams. In the trial, dutasteride failed to reduce the risk of prostate cancer in this subgroup (N. Engl. J. Med. 2010;362:1237–8). The drug reduced the risk only of low-grade tumors, not the risk of lethal tumors, Dr. Walsh noted.
The study included men at high risk because of their age (50–75 years), an elevated PSA level, and a prostate biopsy within the preceding 6 months due to suspicion of prostate cancer, Dr. Andriole and his colleagues said (N. Engl. J. Med. 2010;362:1192–202). After randomization, 3,305 men were assigned to oral dutasteride and 3,424 to placebo. They were followed every 6 months using digital exams, PSA testing, and the International Prostate Symptom Score (IPSS). They underwent ultrasound assessment at baseline, 2 years, and 4 years, as well as transrectal, ultrasound-guided biopsy at 2 and 4 years, or at any time the procedure was clinically indicated. The primary end point was prostate cancer detected on these biopsies.
In all, 659 men in the dutasteride group (19.9%) and 858 in the placebo group (25.1%) were found to have prostate cancer on biopsy. The risk of the malignancy was lower than the risk in the placebo group regardless of patient age, family history of prostate cancer, baseline PSA level, baseline prostate volume, body mass index, or baseline IPSS, the investigators said. Mortality was not significantly different between men taking dutasteride (1.7%) and those taking placebo (1.9%), and there were no deaths from prostate cancer. The number of high-grade tumors also was not significantly different between the two groups.
Dutasteride reduced the risk of acute urinary retention, urinary tract infection, and the need for surgery to address benign prostatic hyperplasia. However, this benefit may have been offset by increases in loss of libido and erectile dysfunction. The drug was associated with an unexpected rise in the composite end point of “cardiac failure,” which included heart failure, ventricular failure, cardiopulmonary failure, and congestive cardiomyopathy. However, it did not raise the rate of cardiovascular events or cardiovascular mortality, compared with placebo. Fewer than 5% of the men taking dutasteride discontinued the medication, they added.
In his editorial, Dr. Walsh noted that “as the authors point out,” the reduction in prostate cancer “most likely represents shrinkage or inhibition of the growth of existing tumors rather than prevention of cancer.” Like the related drug finasteride, dutasteride “merely temporarily shrink[s] tumors that have a low potential for being lethal,” he said. Moreover, using either drug “may be somewhat risky” because both suppress PSA levels, which may give patients a false sense of security. “And if prostate cancer develops, the diagnosis may be delayed until they have high-grade disease that may be difficult to cure,” Dr. Walsh added.
Disclosures: The study was designed and funded by GlaxoSmithKline. Dr. Andriole reported receiving fees from GlaxoSmithKline and several other pharmaceutical companies, as well as owning stock or stock options in Cambridge Endo, Envisioneering Medical Technologies, and Viking Medical. Dr. Walsh's financial disclosures are available at NEJM.org