Systemic Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update.

Area of Science:

• Oncology
• Genitourinary Cancers
• Prostate Cancer Therapeutics

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) presents complex treatment challenges.
• Prior treatment history significantly influences the efficacy of subsequent therapies.
• Evolving therapeutic options require updated evidence-based recommendations.

Purpose of the Study:

• To establish evidence-based treatment recommendations for patients with mCRPC.
• To guide clinical decision-making for oncologists and patient care teams.
• To incorporate recent advancements in mCRPC therapy.

Main Methods:

• Systematic review of existing evidence.
• Expert Panel review, including patient representation.
• Formulation of clinical recommendations based on synthesized data.

Main Results:

• Androgen receptor pathway inhibitors (ARPIs), PARP inhibitors (PARPi), chemotherapy (docetaxel, cabazitaxel), and radiopharmaceuticals (radium 223, 177Lu-PSMA-617) demonstrate overall survival (OS) benefits in mCRPC.
• Combinations of ARPIs and PARPi show benefit in BRCA-altered mCRPC.
• Specific agents like olaparib, pembrolizumab, and radium 223 are recommended for distinct patient subgroups based on genetic alterations and prior treatments.

Conclusions:

• Treatment sequencing for mCRPC depends on prior systemic therapy for castration-sensitive disease.
• Androgen-deprivation therapy should be continued indefinitely; early genetic testing and palliative care are advised.
• Specific recommendations include ARPI + PARPi for ARPI-naive BRCA-altered mCRPC, docetaxel after prior ARPI, and 177Lu-PSMA-617 or cabazitaxel after prior ARPI and docetaxel.