Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials

Introduction: To compare the efficacy of abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 in the treatment of castration-resistant, docetaxel-resistant metastatic prostate cancer. Methods: An indirect comparison of Overall Survival (OS) and time to PSA progression among abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 was performed with a network metaanalysis. OS in the entire population of patients was the primary endpoint. OS in ECOG 0-1/2, BPISF≤ 4/>4, pretreated with 1 or 2 courses of chemotherapy, age≤65/>65 patients, patients with only bone metastases or bone and visceral metastases, and time to PSA progression were the secondary endpoints. An indirect comparison of the Hazard Ratio and the 95% Confidence Interval was performed, assuming an alpha error of 5% as an index of statistical significance. The among-the-trial heterogeneity was assessed using a qualitative methodological and clinical analysis. Results: Four trials were selected. In three trials, the comparator was placebo, in one trial it was mitoxantrone, the effect of which in improving survival was considered negligible. No significant difference in OS among abiraterone acetate, enzalutamide, cabazitaxel and radium 223 was observed in neither the entire population nor all the subgroups of patients. Enzalutamide resulted significantly better than abiraterone acetate, cabazitaxel or radium-223 in time to PSA progression. Conclusion: Since no significant difference in efficacy seems to exist between the four therapeutic options in the treatment of castration-resistant, docetaxel-resistant, metastatic prostate cancer, the safety of the treatment, patient's compliance and costs should represent the criteria to guide clinicians' choice in clinical practice.