Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer

Although immunotherapy has transformed the treatment of several genitourinary malignancies, its role in prostate cancer remains limited. Combining immunotherapy with targeted therapies has emerged as a promising approach to enhance immune responses in prostate cancer. We aimed to systematically evaluate the efficacy and safety of immunotherapy combined with targeted therapy in the treatment of prostate cancer. We conducted a detailed literature search across Embase, Scopus, PubMed, Web of Science, and the Cochrane Library to include clinical trials enrolling adults with histologically confirmed prostate cancer treated with a combination of targeted therapy and immunotherapy. A systematic review and meta-analysis were performed according to a registered protocol. A total of 21 studies from 19 clinical trials, encompassing 5702 participants, were included. The studies evaluated 12 unique therapeutic combinations involving six targeted agents and four immunotherapies. Seven trials compared combination therapy with monotherapy. Pooled analyses showed that combination therapy significantly improved disease control rate (RR = 1.42), complete response (RR = 2.56), and partial response (RR = 2.13), albeit with a higher incidence of adverse events. In single-arm studies, the pooled median progression-free survival was 5.14 months, and median overall survival was 16.79 months. The androgen receptor signaling inhibitor subgroup exhibited longer survival than the PARP inhibitor subgroup. Combination immunotherapy and targeted therapy demonstrate superior efficacy over monotherapy in prostate cancer but increase the risk of toxicity. These promising results warrant further validation in large-scale, well-designed randomized trials.