RENAL AND UROLOGICAL PROBLEMS: Edited by Fred Saad and Andrea KokorovicMetastatic castrate-resistant prostate cancer: a new horizon beyond the androgen receptorsRoy, Soumyajita; Saad, Fredb Author Information aDepartment of Radiation Oncology, Rush University Medical Center, Chicago, Illinois, USA bDepartment of Surgery, Université de Montréal, Montreal, Quebec, Canada Correspondence to Fred Saad, MD, FRCSC, Dr, Division of Urology, University of Montreal Hospital Center, CHUM, Pavillon R, 900, Rue St-Denis, Porte R04-446, Montréal, QC, Canada H2X 0A9. Tel: +1 514 890 8000; fax: +1 514 412 7620; e-mail: [email protected] Current Opinion in Supportive and Palliative Care: December 2022 - Volume 16 - Issue 4 - p 223-229 doi: 10.1097/SPC.0000000000000620 Buy Metrics Abstract Purpose of review Systemic chemotherapy and second-generation androgen receptor-axis targeted therapies have been in the forefront of management for metastatic castrate-resistant prostate cancer (mCRPC) patients with low or high symptom burden. However, in the recent past, due to improvement in molecular characterization, management of mCRPC has witnessed long strides of advancement. We aim to review the novel nonhormonal and nonchemotherapeutic treatment options. Recent findings Poly (ADP-ribose) polymerase inhibitors (PARPis) such as olaparib and rucaparib have been recently approved by the US FDA for use in mCRPC with germline or somatic mutations in homologous recombination repair. The combination of PARPi with androgen receptor axis-targeted agents (ARAT) or dual ARAT-based therapy has shown superior radiographic progression-free survival as a first-line treatment. A combination of AKT inhibitor ipatasertib and abiraterone has shown improvement in radiographic progression-free survival as a first-line treatment. Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical like 177Lu-PSMA-617, a beta particle emitter has demonstrated improvement in overall survival in mCRPC patients pretreated with ARAT or taxanes. Although immune checkpoint inhibitors are being tested in mCRPC, there is no robust evidence to support this premise. Summary These new agents have widened the treatment options for mCRPC patients. Overall treatment should be focused on improving survival while limiting the deterrent effect on the quality of life. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.