Treatment of Metastatic Castration-Resistant Prostate Cancer

Introduction to Treatment Options

The National Comprehensive Cancer Network recommends abiraterone plus prednisone or enzalutamide as first-line therapy for patients in good health with increasing metastatic castration-resistant prostate cancer, with continuation of androgen deprivation therapy indefinitely 1, 2

Androgen deprivation therapy (ADT) must be continued indefinitely regardless of any additional therapies added, as recommended by the Journal of Clinical Oncology 2, 3
The American College of Clinical Oncology verifies that serum testosterone remains <50 ng/dL before diagnosing castration resistance and throughout treatment, as stated in the Journal of the National Comprehensive Cancer Network 1, 3

For asymptomatic or minimally symptomatic patients, the American Urological Association recommends abiraterone acetate 1000 mg daily plus prednisone 5 mg twice daily, which demonstrates improved overall survival (OS), quality of life, and favorable benefit-harm balance 2, 4
The American Society of Clinical Oncology recommends enzalutamide 160 mg daily, which demonstrates improved OS, quality of life, and favorable benefit-harm balance, with strong evidence (evidence strength: strong; recommendation strength: strong) 2

For patients with high-volume disease who are fit for chemotherapy, the National Comprehensive Cancer Network recommends triplet therapy with ADT plus docetaxel plus either abiraterone or darolutamide, which improves OS over ADT with docetaxel alone (Category 1, preferred) 1

The American College of Radiology recommends that all patients with mCRPC and bony metastases should receive a bone-protective agent (zoledronic acid or denosumab), with zoledronic acid 4 mg every 3-4 weeks being the only bisphosphonate with proven clinical benefit in reducing skeletal complications in hormone-refractory prostate cancer 9

Asymptomatic, chemotherapy-naïve patients with good performance status can expect median survival of 30-35+ months with modern ARPI therapy, as reported by the Journal of the National Comprehensive Cancer Network 5
Patients receiving sequential multiple lines of therapy can often achieve 5+ years of survival, according to the Journal of Clinical Oncology 5

The American Society of Clinical Oncology advises to never discontinue ADT even when adding novel therapies—maintaining castrate testosterone levels is essential for optimal outcomes 3
The National Comprehensive Cancer Network recommends avoiding estramustine due to increased risk of clinically important toxicities without evidence of improved survival 6
The Journal of Clinical Oncology advises not to offer sipuleucel-T to symptomatic patients as it is only indicated for asymptomatic or minimally symptomatic disease 4