The optimal upfront therapy in metastatic hormone-sensitive prostate cancer: A network meta-analysis

Background: Prostate cancer (PC) is one of the most common cancer types in men. In addition to androgen-deprivation therapy (ADT), new generation agents have provided survival advantages to patients with metastatic hormone-sensitive PC (mHSPC). In this analysis, we aimed to determine the most effective approach for treating and suppressing mHSPC using network meta-analysis (NMA). Materials and Methods: A total of 10 trials investigating different treatment modalities were conducted using NMA. The analysis was performed for all mHSPC cases as well as for low- and high-volume and docetaxel-naive subgroups. Results: In combination with ADT, abiraterone acetate (AA) in the general-population and high-volume-disease subgroups, and enzalutamide in docetaxel-naive and low-volume-disease subgroups have the highest probability of being the best treatment modalities in terms of overall survival. In addition, in the low-volume and docetaxel-naive settings, enzalutamide was superior to ADT (hazard ratio [HR] = 0.429, 95% CrI: 0.258-0.714 and HR = 0.533, 95% CrI: 0.375-0.756, respectively). In addition, in the high-volume and general-population settings (all trials and cases), AA was superior to ADT (HR = 1.568, 95% CrI: 1.378-1.773 and HR = 1.164, 95%CrI: 1.348-1.924, respectively). Conclusion: The volume status based on the CHAARTED trial should be taken into account to determine an appropriate treatment strategy for mHSPC. AA plus prednisone in high-risk and high-volume-mHSPC patients and enzalutamide in low-volume-mHSPC patients could be favorable options in combination with ADT. Depending on the patient's tolerance, in high-volume mHSPC, docetaxel, or apalutamide in combination with ADT could be alternatives for AA, whereas in the low-volume mHSPC, local radiotherapy plus ADT or ADT alone could be utilized in place of enzalutamide.