To provide evidence-based recommendations for patients with metastatic castration-resistant prostate cancer (mCRPC).
An Expert Panel including patient representation completed a systematic review of the evidence and made recommendations.
Depending upon prior treatment received, androgen receptor pathway inhibitors (ARPIs: enzalutamide, abiraterone with prednisone), poly(ADP-ribose) polymerase inhibitors (PARPi), chemotherapeutic agents (docetaxel, cabazitaxel), radiopharmaceuticals (radium 223, 177Lu-prostate-specific membrane antigen [PSMA]-617), and sipuleucel-T have demonstrated an overall survival (OS) benefit for patients with mCRPC. For patients with BRCA1/2 alterations who did not receive prior ARPI, the combination of PARPi and ARPI (talazoparib + enzalutamide, olaparib and/or niraparib + abiraterone) has shown clinical benefit. For patients with BRCA1/2 alterations who received prior ARPI or ARPI followed by docetaxel, olaparib showed OS benefit. In select patients with microsatellite instability-high/mismatch repair-deficient, pembrolizumab showed clinical efficacy.
Prior systemic therapy for castration-sensitive prostate cancer will determine subsequent therapy used for mCRPC. Continue androgen-deprivation therapy for patients with mCRPC indefinitely. Early adoption of somatic genetic testing and palliative care is recommended. Patients with mCRPC and bony metastases should receive a bone-protective agent. The panel recommends the combination of ARPI with PARPi in patients with BRCA1/2 alterations who did not receive prior ARPI. For patients who received prior ARPI, the panel recommends docetaxel chemotherapy. The panel recommends 177Lu-PSMA-617 or cabazitaxel chemotherapy for patients who receive prior ARPI and docetaxel chemotherapy. For patients with BRCA1/2 alterations who received prior ARPI, the panel recommends PARPi monotherapy. Radium 223 is recommended for patients with symptomatic bone-only disease. Evidence for optimal sequencing for mCRPC regimens is lacking.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2025 May 02 [Epub ahead of print]
Rohan Garje, Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, R Bryan Rumble, Mary-Ellen Taplin, Terry M Kungel, Daniel Herchenhorn, Tian Zhang, Kathryn E Beckermann, Neha Vapiwala, Michael A Carducci, Paul Celano, Sebastien J Hotte, Arnab Basu, Hala Borno, Alan H Bryce, Peng Wang, Elizabeth Wulff-Burchfield, Lisa Bodei, Andrew Loblaw, Robert J Hamilton, Hamid Emamekhoo, Thomas A Hope, Huan He, M Hassan Murad, Hongfang Liu, James Elbert Williams, Rahul A Parikh
Miami Cancer Institute, Baptist Health South Florida, Miami, FL., Mayo Clinic, Phoenix, AZ., American Society of Clinical Oncology, Alexandria, VA., Dana-Farber Cancer Institute, Boston, MA., Patient representative, Woolwich, ME., Instituto D'Or/Oncologia D'Or, Latin America Cooperative Group (LACOG)- Genito-Urinary, Rio de Janeiro, Brazil., Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX., Vanderbilt University School of Medicine, Nashville, TN., University of Pennsylvania Abramson Cancer Center, Philadelphia, PA., Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD., Greater Baltimore Medical Center (GBMC), Towson, MD., McMaster University, Hamilton, Ontario, Canada., University of Alabama at Birmingham, Birmingham, AL., University of California, San Francisco, San Francisco, CA., City of Hope Cancer Center, Goodyear, AZ., Ohio State University Wexner Medical Center, Columbus, OH., University of Kansas Medical Center, Westwood, KS., Weill Cornell Medical College of Cornell University, Memorial Sloan Kettering Cancer Center, New York, NY., Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada., University of Wisconsin, Madison, WI., Yale University, New Haven, CT., Mayo Clinic, Rochester, MN., SPHR Pennsylvania Prostate Cancer Coalition, Camp Hill, PA.