Non‐steroidal antiandrogen monotherapy compared with luteinizing hormone‐releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review

To assess the effects of non‐steroidal antiandrogen monotherapy compared with luteinizing hormone‐releasing hormone agonists or surgical castration monotherapy for treating advanced hormone‐sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non‐steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone‐sensitive stages of prostate cancer. Two review authors independently examined full‐text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed‐effect model as primary analysis (when heterogeneity was low with I2 < 50%); we used a random‐effects model when confronted with substantial or considerable heterogeneity (when I2 ≥50%). A total of 11 studies involving 3060 randomly assigned participants were included in the present review. Use of non‐steroidal antiandrogens resulted in lower overall survival times (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.05–1.48, six studies, 2712 participants) and greater clinical progression (1 year: risk ratio [RR] 1.25, 95% CI 1.08–1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08–1.45, six studies, 2373 participants; 2 years: RR 1.14, 95% CI 1.04–1.25, three studies, 1336 participants), as well as treatment failure (1 year: RR 1.19, 95% CI 1.02–1.38, four studies, 1539 participants; 70 weeks: RR 1.27, 95% CI 1.05–1.52, five studies, 1845 participants; 2 years: RR 1.14, 95% CI 1.05–1.24, two studies, 808 participants), compared with medical or surgical castration. The quality of evidence for overall survival, clinical progression and treatment failure was rated as moderate according to GRADE. Use of non‐steroidal antiandrogens increased the risk for treatment discontinuation as a result of adverse events (RR 1.82, 95% CI 1.13–2.94, eight studies, 1559 participants), including events such as breast pain (RR 22.97, 95% CI 14.79– 35.67, eight studies, 2670 participants) and gynaecomastia (RR 8.43, 95% CI 3.19–22.28, nine studies, 2774 participants) The risk of other adverse events, such as hot flushes (RR 0.23, 95% CI 0.19–0.27, nine studies, 2774 participants) was decreased when non‐steroidal antiandrogens were used. The quality of evidence for breast pain, gynaecomastia and hot flushes was rated as moderate according to GRADE. The effects of non‐steroidal antiandrogens on cancer‐specific survival and biochemical progression remained unclear. Non‐steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation resulting from adverse events. Evidence quality was rated as moderate according to GRADE; therefore, further research is likely to have an important impact on results for patients with advanced but non‐metastatic prostate cancer treated with non‐steroidal antiandrogen monotherapy.