Optimization of therapies for men with advanced prostate cancer: a review of recent developments with a look toward the future.

Abstract

Summarizes the rapid progress being made in treatment of advanced prostate cancer. Debate remains regarding the optimal sequencing of therapies in metastatic castration-sensitive prostate cancer with attention focused on the use of abiraterone versus docetaxel. Randomized trials now show a potential advantage to next-generation antiandrogens in the setting of nonmetastatic castration-resistant prostate cancer. Patient-specific genomic anomalies, in particular DNA repair defects, provide targets for therapy with poly(ADP-ribose) polymerase inhibitors alone and in combination with other interventions. Adjustments in the dose and administration schedule of the accompanying steroid may improve the efficacy of abiraterone. Novel radiopharmaceuticals and immunotherapies suggest progress is on the horizon for men with castration-resistant prostate cancer. In this review, we will highlight the avenues of research leading to optimization of therapies for men with advanced prostate cancer. Known therapeutics, such as docetaxel and abiraterone, are being used earlier in the disease course in the setting of metastatic castration-sensitive prostate cancer, and next-generation antiandrogens in the setting of nonmetastatic castration-resistant disease. Existing interventions are being optimized, including a maneuver to salvage abiraterone response with steroid switch. Finally, individualized therapies directed at specific genomic aberrations, a radiopharmaceutical targeting prostate-specific membrane antigen, and immune therapy combinations are providing potentially additional treatment options for patients with refractory disease.