Adjunct to active surveillance?

Adjunct to active surveillance?

Low-risk prostate cancers are nonpalpable, low-grade tumors associated with prostate-specific antigen (PSA) levels less than 10 ng/mL. For these patients, active surveillance is an option, allowing a period of observation to help decide who should be treated or not treated. Generally, this involves repeated biopsy sampling with the option to treat more aggressively if higher grade tumors are found. Active surveillance is more frequently utilized in Europe and Canada than in the United States, where more aggressive treatment is the norm. A new study from the U.S. and Canada investigates the safety and efficacy of the 5α-reductase inhibitor dutasteride on prostate cancer progression in men with low-risk disease. A total of 302 men ages 48-82 with low-volume Gleason score 5-6 prostate cancer were randomized to dutasteride 0.5 mg per day or placebo. Patients were followed for 3 years with prostate biopsies done at 18 months and 3 years with the primary endpoint being time to prostate cancer progression. After 3 years, 38% of men in the dutasteride group and 48% of men in the control group had prostate cancer progression (hazard ratio 0.62; 95% confidence interval [CI], 0.43-0.9; P = 0.009). Dutasteride was not associated with an increase in adverse events. There were no prostate cancer-related deaths and no incidence of metastatic disease in either group. The authors conclude that "dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer" (Lancet published online January 23, 2012). An accompanying editorial points out the appeal of a safe oral drug that can prevent prostate cancer progression, but the author cannot recommend the drug based on this study due to several limitations — short duration, no evidence of mortality difference, and, most importantly, the risk that 5α-reductase inhibitors may decrease the volume of low-grade, but not high-grade, cancers (Lancet published online January 23, 2012). This study comes at a time when physicians are actively debating the pros and cons of screening for prostate cancer. The recently published PLCO trial showed that PSA screening does not lower the risk for death from prostate cancer while there is evidence of harm (J Natl Cancer Inst 2012;104:125-132). Some would argue that rather than treating low-grade prostate cancers, it may be better not to diagnose it at all. This issue is sure to be a topic of discussion at the FDA if GlaxoSmithKline requests approval for dutasteride (Avodart) for the management of low-risk prostate cancer.