Castration-Resistant Prostate Cancer (CRPC): When Hormone Therapy Stops Working
- What is castration-resistant prostate cancer (CRPC)?
- How is CRPC diagnosed?
- Non-metastatic CRPC (nmCRPC) – high-risk features
- Metastatic CRPC (mCRPC) – treatment landscape
- Treatment options for mCRPC
- Prognosis – survival by risk factors
- Clinical trials – importance of research
- Interactive FAQ – 9 questions about CRPC
What is castration-resistant prostate cancer (CRPC)?
Castration-resistant prostate cancer (CRPC) is prostate cancer that continues to progress despite having castrate levels of testosterone (<50 ng/dL). It is also called hormone-refractory prostate cancer.
CRPC can be:
- Non-metastatic CRPC (nmCRPC): Rising PSA but no visible metastases on imaging
- Metastatic CRPC (mCRPC): Visible metastases (bone, lymph nodes, viscera)
CRPC is NOT the same as castration-sensitive prostate cancer (which still responds to ADT). It represents a more aggressive phase of the disease.
How is CRPC diagnosed?
CRPC is diagnosed when ALL of the following are present:
- Castrate testosterone level: <50 ng/dL (confirmed)
- Progression: One or more of:
- PSA progression: 2 consecutive rises (≥25% above nadir, absolute increase ≥2 ng/mL)
- Radiographic progression: New metastases on CT, bone scan, or PSMA PET
- Clinical progression: New cancer-related symptoms (bone pain, urinary obstruction)
Staging for CRPC:
- PSMA PET/CT: Most sensitive for detecting metastases
- CT chest/abdomen/pelvis: For lymph nodes and visceral metastases
- Bone scan: For bone metastases
Non-metastatic CRPC (nmCRPC) – high-risk features
nmCRPC is defined by PSA rise without visible metastases. Treatment is recommended for patients at high risk of developing metastases.
High-risk features (PSA doubling time <10 months):
- PSA doubling time <10 months is associated with high risk of metastasis and death
- All patients with nmCRPC should have PSA checked every 3 months
Treatment options for nmCRPC:
- Apalutamide (Erleada): Oral anti-androgen – improves metastasis-free survival (SPARTAN trial)
- Enzalutamide (Xtandi): Oral anti-androgen – improves metastasis-free survival (PROSPER trial)
- Darolutamide (Nubeqa): Oral anti-androgen – improves metastasis-free survival (ARAMIS trial)
No active surveillance:
- nmCRPC with PSA doubling time <10 months should be treated (not watched)
- Treatment reduces risk of metastasis by 70-80%
Metastatic CRPC (mCRPC) – treatment landscape
mCRPC is prostate cancer that has spread despite castrate testosterone. It is incurable but treatable with multiple lines of therapy.
Prognostic factors in mCRPC:
- Good prognosis: Asymptomatic, no visceral metastases, long response to ADT
- Poor prognosis: Symptomatic, visceral metastases (liver, lung), short response to ADT
Treatment options for mCRPC
Multiple effective treatments are available for mCRPC. Sequencing is key.
First-line mCRPC options (choose based on prior treatments):
- Abiraterone (Zytiga) + prednisone: Oral androgen biosynthesis inhibitor – if not used in mHSPC
- Enzalutamide (Xtandi): Oral anti-androgen – if not used in mHSPC
- Docetaxel (chemotherapy): Especially for symptomatic disease or visceral metastases
Second-line mCRPC options (after docetaxel):
- Cabazitaxel (Jevtana): Chemotherapy for post-docetaxel progression
- Abiraterone or enzalutamide: If not used previously
- Radium-223 (Xofigo): For bone-only metastases (no visceral disease)
Third-line and beyond mCRPC options:
- PARP inhibitors (olaparib, rucaparib): For HRR mutations (BRCA, ATM, PALB2) – requires genetic testing
- Lu-177-PSMA (Pluvicto): Radioligand therapy for PSMA-positive disease
- Pembrolizumab (Keytruda): Only for MSI-H/dMMR tumors (rare)
Bone health management (all mCRPC patients):
- Denosumab (Prolia, Xgeva) 120 mg SC every 4 weeks – reduces skeletal-related events
- Zoledronic acid (Zometa) 4 mg IV every 4 weeks – alternative
- Calcium + vitamin D supplementation
Prognosis – survival by risk factors
Survival for mCRPC varies significantly by patient characteristics:
- Good risk (asymptomatic, no visceral metastases): Median survival 3-5 years
- Poor risk (symptomatic, visceral metastases): Median survival 1-2 years
- BRCA2 mutations: More aggressive but respond to PARP inhibitors
Response to treatment:
- PSA response (≥50% decline) correlates with improved survival
- Duration of response varies (6-12 months per line of therapy)
Clinical trials – importance of research
Patients with mCRPC should consider clinical trials, especially after approved options are exhausted.
Active areas of research:
- Novel anti-androgens (next-generation)
- Combination therapies (PARP inhibitor + anti-androgen)
- Immunotherapy combinations
- Targeted radioligand therapies (new isotopes)
How to find clinical trials:
- ClinicalTrials.gov
- Major cancer centres (MD Anderson, Memorial Sloan Kettering, Mayo Clinic)
- Ask your oncologist about available trials
Interactive FAQ – Castration-resistant prostate cancer
Prostate cancer that progresses despite castrate testosterone levels (<50 ng/dL). It can be non-metastatic (nmCRPC) or metastatic (mCRPC).
Castrate testosterone + PSA progression OR radiographic progression OR new symptoms.
nmCRPC: rising PSA without visible metastases. mCRPC: visible metastases on imaging (bone, lymph nodes, viscera).
Apalutamide, enzalutamide, or darolutamide – all delay metastasis in high-risk patients (PSA doubling time <10 months).
Abiraterone, enzalutamide, or docetaxel – choice depends on prior treatments and symptoms.
Yes – for patients with HRR mutations (BRCA, ATM, PALB2). Genetic testing is required.
Good risk: 3-5 years. Poor risk (symptomatic, visceral metastases): 1-2 years.
Yes – ADT is continued indefinitely to maintain castrate testosterone levels.
Treated – especially if PSA doubling time <10 months. Treatment delays metastasis and improves survival.
Disclaimer: This information is for educational purposes. CRPC is a complex disease state requiring multidisciplinary care. Consult a medical oncologist at Vivekananda Hospital.