BACKGROUND

Optimal treatment selection for metastatic castration resistant prostate cancer (mCRPC) remains challenging due to evolving standards of care in castration sensitive setting.

PURPOSE

To synthesize and appraise evidence on systemic therapy for mCRPC patients stratified by prior therapy and alterations informing a clinical practice guideline.

DATA SOURCES

MEDLINE and EMBASE (inception to 5 March 2025) using living search.

STUDY SELECTION

Randomized clinical trials assessing systemic therapy in mCRPC.

DATA EXTRACTION

Primary outcomes assessed were progression free survival (PFS) and overall survival (OS).

DATA SYNTHESIS

This report of the living systematic review (LSR) includes 143 trials with 17,523 patients (59 phase III/IV trials, 8,941 patients; 84 phase II, 8,582 patients). In the setting of prior androgen deprivation therapy (ADT) alone or ADT+docetaxel, treatment benefit was observed with poly (ADP-ribose) polymerase inhibitors (PARPi) in combination with androgen receptor pathway inhibitors (ARPI) for + subgroup. In the setting of prior ADT+ARPI or ADT+ARPI+docetaxel, treatment benefit was observed with PARPi monotherapy for + subgroup. Treatment benefit with PARPi may be observed for select non- homologous recombination repair () alterations (, ). Treatment benefit was observed with abiraterone, enzalutamide, cabazitaxel, docetaxel (if no prior docetaxel), and Lu (if PSMA+) for patients without alterations.

LIMITATIONS

Study-level data and indirectness in evidence.

CONCLUSION

Findings from the current LSR suggest that optimal treatment for mCRPC should be individualized based on prior therapy and alterations. Current evidence favors PARPi alone (ARPI exposed) or in combination with ARPI (ARPI naïve) for patients with alterations, while ARPI alone, chemotherapy, and Lu remain potential options for patients without alterations.