Metastatic Castration-Resistant Prostate Cancer (mCRPC)
mCRPC develops when prostate cancer progresses despite castrate levels of testosterone (<50 ng/dL). Treatment goals include prolonging survival, controlling symptoms, and maintaining quality of life through sequential androgen receptor (AR) pathway inhibitors, chemotherapy, targeted agents, and radioligand therapy.
Workup
- Confirm castrate testosterone (<50 ng/dL) while on LHRH therapy or after orchiectomy
- Serial PSA, alkaline phosphatase, LDH
- Imaging (CT, bone scan, PSMA-PET) to assess disease burden
- Germline and somatic genomic testing (BRCA1/2, ATM, CDK12, MSI-H, TMB) to guide targeted therapy
- Evaluate symptoms (pain, spinal cord compression risk)
Treatment Options
Continue Androgen Deprivation Therapy (ADT)
- Maintain LHRH agonist/antagonist or orchiectomy throughout treatment
AR Pathway Inhibitors
- Abiraterone + prednisone or enzalutamide as first-line options
- Apalutamide/ darolutamide less common in mCRPC but used earlier
- Sequence AR inhibitors after discussion of prior exposure/resistance
Chemotherapy
- Docetaxel (if not given in metastatic hormone-sensitive setting) followed by cabazitaxel
- Cabazitaxel preferred over additional AR inhibitors after AR-target failure (CARD trial)
Targeted & Immunotherapy
- PARP inhibitors (olaparib, rucaparib, talazoparib + enzalutamide) for BRCA1/2 or other HRR-mutated tumors
- Pembrolizumab for MSI-H/TMB-high disease
- Sipuleucel-T for asymptomatic/minimally symptomatic mCRPC
- 177Lu-PSMA-617 radioligand therapy after AR inhibitor and taxane therapy for PSMA-positive disease
Bone Health & Symptom Management
- Denosumab or zoledronic acid to prevent skeletal-related events
- External beam radiation for painful lesions, spinal cord compression prophylaxis
- Manage fatigue, anemia, neuropathy, hot flashes, mood changes
- Palliative care integration early
Living with mCRPC
- Track PSA trend, imaging, testosterone, CBC, LFTs, bone scans, medications, side effects, pain scores, functional status (ECOG)
- Maintain activity and nutrition; address sexual health, urinary symptoms
- Support mental health and caregiving needs
- Discuss clinical trial availability at each progression point
Complications
- Bone metastasis pain, fractures, spinal cord compression
- Cytopenias from therapy, infections
- Cardiovascular/metabolic effects from ADT
- Fatigue, cognitive changes
Research & Future Directions
PSMA bispecifics, CAR-T cells, AKT/PI3K inhibitors, and combination PARP/AR strategies are under study. Liquid biopsies and PSMA-PET monitoring refine treatment timing.
Experimental & Emerging Treatments
- PSMAxCD3 Bispecific Antibodies: Redirect T cells to PSMA-expressing cells.
- CAR-T & CAR-NK therapies targeting PSMA or STEAP1.
- AKT Inhibitors (ipatasertib, capivasertib) with AR inhibitors for PTEN-loss tumors.
- Digital Biomarkers: Wearables + PROs predicting symptomatic progression before imaging.
Track mCRPC with Diagnoza.care
Sequence Therapies with Confidence – Log PSA, testosterone, genomic findings, systemic therapies, bone-modifying agents, imaging dates, pain scores, supportive meds, and trial options; capture side effects; and let the AI companion remind you of labs, scans, and symptom surveys.
Medical Disclaimer: Informational only. Work with your medical oncologist for therapy sequencing, genomic testing, symptom management, and trial enrollment.
Sources: NCCN Prostate Cancer Guidelines, ASCO, ESMO