# Metastatic castration-resistant prostate cancer

Source: https://onco.cc/cancers/prostate-mcrpc/  
OnCo record `prostate-mcrpc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Metastatic castration-resistant prostate cancer is disease that grows despite castrate testosterone. Sequenced treatments now include androgen receptor inhibitors, docetaxel and cabazitaxel, PARP inhibitors for men with BRCA-type mutations, the radioligand 177Lu-PSMA-617 and radium-223 for bone-predominant disease.

## Summary

Metastatic castration-resistant prostate cancer is defined by progression on scans or PSA, or new metastases, with castrate testosterone. Nearly every man reaches it from hormone-sensitive disease, and the treatment chosen depends on what he has already had. Men who have not had an androgen receptor pathway inhibitor receive abiraterone or enzalutamide; PROpel, TALAPRO-2 and MAGNITUDE showed that adding olaparib, talazoparib or niraparib helps men with BRCA and other homologous recombination repair mutations, and PROfound showed olaparib alone beats a second hormonal agent in these men. Docetaxel and then cabazitaxel remain the chemotherapies. VISION established 177Lu-PSMA-617 after chemotherapy and PSMAfore moved it before, for PSMA PET-positive disease; 177Lu-PSMA-I&T (SPLASH, ECLIPSE) follows the same path. Radium-223 lengthens life in symptomatic bone-predominant disease without visceral metastases (ALSYMPCA), sipuleucel-T is still approved for minimally symptomatic disease, and pembrolizumab is used for the rare mismatch repair-deficient tumour. Tumour and germline testing for HRR genes and mismatch repair is standard. Actinium-225 PSMA agents, the STEAP1 T-cell engager xaluritamig and the EZH2 inhibitor mevrometostat are in phase 3.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: mCRPC; Metastatic CRPC; Castration-resistant metastatic prostate cancer; Hormone-refractory prostate cancer (older term)
- Tags: subtype-page
- Group: genitourinary
- Burden: The state in which nearly all prostate cancer deaths occur, about 400,000 a year worldwide; median survival from first treatment is now around three years, longer for men who have not had an androgen receptor inhibitor.
- Subtypes: mCRPC, androgen receptor pathway inhibitor-naive; mCRPC after an androgen receptor pathway inhibitor, chemotherapy-naive; mCRPC after taxane chemotherapy; HRR-mutant mCRPC (BRCA1, BRCA2, ATM and others; PARP inhibitors); PSMA PET-positive mCRPC (radioligand therapy); Bone-predominant mCRPC without visceral metastases (radium-223); Mismatch repair-deficient mCRPC (pembrolizumab)
- Biomarkers: Tumour and germline HRR genes (BRCA2 above all); PSMA PET uptake and FDG discordance; Mismatch repair deficiency and tumour mutational burden; PSA and alkaline phosphatase; Circulating tumour DNA (AR amplification, BRCA2 reversion); AR-V7 in circulating tumour cells (research)

## Standard of care

- First line, androgen receptor pathway inhibitor-naive: Abiraterone or enzalutamide; add olaparib, talazoparib or niraparib for HRR-mutant, above all BRCA-mutant, disease (PROpel, TALAPRO-2, MAGNITUDE). ([Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Olaparib](https://onco.cc/drugs/olaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/), [Niraparib](https://onco.cc/drugs/niraparib/), [PROpel](https://onco.cc/trials/propel/), [TALAPRO-2](https://onco.cc/trials/talapro-2/), [MAGNITUDE](https://onco.cc/trials/magnitude/))
- After an androgen receptor pathway inhibitor: Docetaxel; olaparib or rucaparib for BRCA-mutant disease (PROfound); 177Lu-PSMA-617 for PSMA-positive disease before chemotherapy (PSMAfore); pembrolizumab for mismatch repair-deficient tumours. ([Docetaxel](https://onco.cc/drugs/docetaxel/), [Olaparib](https://onco.cc/drugs/olaparib/), [Rucaparib](https://onco.cc/drugs/rucaparib/), [PROfound](https://onco.cc/trials/profound/), [Lutetium-177 vipivotide tetraxetan](https://onco.cc/drugs/pluvicto/), [PSMAfore](https://onco.cc/trials/psmafore/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/))
- After docetaxel: 177Lu-PSMA-617 (VISION), cabazitaxel, radium-223 for symptomatic bone-only disease (ALSYMPCA), or a PARP inhibitor if not yet used. ([Lutetium-177 vipivotide tetraxetan](https://onco.cc/drugs/pluvicto/), [VISION](https://onco.cc/trials/vision/), [Cabazitaxel](https://onco.cc/drugs/cabazitaxel/), [Radium-223 dichloride](https://onco.cc/drugs/radium-223/), [ALSYMPCA](https://onco.cc/trials/alsympca/), [TheraP (ANZUP 1603)](https://onco.cc/trials/therap/))
- Bone health: Denosumab or zoledronic acid to prevent skeletal events, with calcium and vitamin D; palliative radiotherapy to painful metastases. ([Denosumab](https://onco.cc/drugs/denosumab/), [Zoledronic acid](https://onco.cc/drugs/zoledronic-acid/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/))
- Phase 3 options: Actinium-225 PSMA radioligands, the STEAP1 T-cell engager xaluritamig, the EZH2 inhibitor mevrometostat and 177Lu-PSMA-I&T within trials. ([Actinium-225 PSMA agents](https://onco.cc/drugs/ac225-psma/), [Xaluritamig](https://onco.cc/drugs/xaluritamig/), [Mevrometostat](https://onco.cc/drugs/mevrometostat/), [177Lu-PSMA-I&T](https://onco.cc/drugs/lu177-psma-it/), [AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)](https://onco.cc/trials/alphabreak/), [XALute](https://onco.cc/trials/xalute/), [MEVPRO-1](https://onco.cc/trials/mevpro-1/), [SPLASH](https://onco.cc/trials/splash/), [ECLIPSE](https://onco.cc/trials/eclipse-psma/))

## State of the art

- PSMA PET and 177Lu-PSMA-617 make prostate cancer the model for theranostics.
- PARP inhibitors gave prostate cancer its first genotype-directed treatment.
- Survival in this once six-month setting is now measured in years, built from sequenced drugs rather than one breakthrough.

## Open problems

- The best sequence of radioligand, PARP inhibitor and chemotherapy is untested.
- Actinium-225 supply and the lack of alpha-emitter dosimetry.
- Lineage plasticity to neuroendocrine disease under androgen receptor blockade.
- Resistance to 177Lu-PSMA-617 in PSMA-low or FDG-discordant disease.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer
- NCCN Guidelines: Prostate Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459

## Connected records

- drugs: [177Lu-PSMA-I&T](https://onco.cc/drugs/lu177-psma-it/), [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Actinium-225 PSMA agents](https://onco.cc/drugs/ac225-psma/), [BMS-986365](https://onco.cc/drugs/bms-986365/), [Cabazitaxel](https://onco.cc/drugs/cabazitaxel/), [Denosumab](https://onco.cc/drugs/denosumab/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [FPI-2265](https://onco.cc/drugs/fpi-2265/), [HS-20093](https://onco.cc/drugs/hs-20093/), [Ifinatamab deruxtecan](https://onco.cc/drugs/ifinatamab-deruxtecan/), [Lutetium-177 vipivotide tetraxetan](https://onco.cc/drugs/pluvicto/), [Mevrometostat](https://onco.cc/drugs/mevrometostat/), [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Opevesostat](https://onco.cc/drugs/opevesostat/), [Pasritamig](https://onco.cc/drugs/pasritamig/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Radium-223 dichloride](https://onco.cc/drugs/radium-223/), [Rucaparib](https://onco.cc/drugs/rucaparib/), [Saruparib](https://onco.cc/drugs/saruparib/), [Sipuleucel-T](https://onco.cc/drugs/sipuleucel-t/), [Talazoparib](https://onco.cc/drugs/talazoparib/), [Xaluritamig](https://onco.cc/drugs/xaluritamig/), [Zoledronic acid](https://onco.cc/drugs/zoledronic-acid/)
- trials: [AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)](https://onco.cc/trials/alphabreak/), [ALSYMPCA](https://onco.cc/trials/alsympca/), [ECLIPSE](https://onco.cc/trials/eclipse-psma/), [MAGNITUDE](https://onco.cc/trials/magnitude/), [MEVPRO-1](https://onco.cc/trials/mevpro-1/), [PROfound](https://onco.cc/trials/profound/), [PROpel](https://onco.cc/trials/propel/), [PSMAfore](https://onco.cc/trials/psmafore/), [SPLASH](https://onco.cc/trials/splash/), [TALAPRO-2](https://onco.cc/trials/talapro-2/), [TheraP (ANZUP 1603)](https://onco.cc/trials/therap/), [VISION](https://onco.cc/trials/vision/), [XALute](https://onco.cc/trials/xalute/)
- technologies: [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/)
- cancers: [Prostate cancer](https://onco.cc/cancers/prostate/)

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JSON: https://onco.cc/api/v1/entities/prostate-mcrpc.json