{"entity":{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","aka":["mCRPC","Metastatic CRPC","Castration-resistant metastatic prostate cancer","Hormone-refractory prostate cancer (older term)"],"tldr":"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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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)"],"standardOfCare":[{"setting":"First line, androgen receptor pathway inhibitor-naive","approach":"Abiraterone or enzalutamide; add olaparib, talazoparib or niraparib for HRR-mutant, above all BRCA-mutant, disease (PROpel, TALAPRO-2, MAGNITUDE).","refs":["abiraterone","enzalutamide","olaparib","talazoparib","niraparib","propel","talapro-2","magnitude"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After an androgen receptor pathway inhibitor","approach":"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.","refs":["docetaxel","olaparib","rucaparib","profound","pluvicto","psmafore","pembrolizumab"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After docetaxel","approach":"177Lu-PSMA-617 (VISION), cabazitaxel, radium-223 for symptomatic bone-only disease (ALSYMPCA), or a PARP inhibitor if not yet used.","refs":["pluvicto","vision","cabazitaxel","radium-223","alsympca","therap"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Bone health","approach":"Denosumab or zoledronic acid to prevent skeletal events, with calcium and vitamin D; palliative radiotherapy to painful metastases.","refs":["denosumab","zoledronic-acid","sbrt"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Phase 3 options","approach":"Actinium-225 PSMA radioligands, the STEAP1 T-cell engager xaluritamig, the EZH2 inhibitor mevrometostat and 177Lu-PSMA-I&T within trials.","refs":["ac225-psma","xaluritamig","mevrometostat","lu177-psma-it","alphabreak","xalute","mevpro-1","splash","eclipse-psma"]}],"stateOfArt":["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."],"history":[{"year":2004,"title":"TAX 327: docetaxel is the first drug to lengthen life in castration-resistant disease","refs":["docetaxel"]},{"year":2010,"title":"Cabazitaxel and sipuleucel-T approved","refs":["cabazitaxel","sipuleucel-t"]},{"year":2011,"title":"Abiraterone approved after docetaxel","refs":["abiraterone"]},{"year":2012,"title":"Enzalutamide approved","refs":["enzalutamide"]},{"year":2013,"title":"ALSYMPCA: radium-223, the first alpha emitter","refs":["alsympca","radium-223"]},{"year":2020,"title":"PROfound: olaparib for HRR-mutant disease","refs":["profound","olaparib"]},{"year":2021,"title":"VISION: 177Lu-PSMA-617 lengthens life","refs":["vision","pluvicto"]},{"year":2022,"title":"PROpel and MAGNITUDE: PARP inhibitor plus abiraterone","refs":["propel","magnitude"]},{"year":2023,"title":"PSMAfore and TALAPRO-2","refs":["psmafore","talapro-2"]},{"year":2025,"title":"ECLIPSE: 177Lu-PSMA-I&T meets its endpoint","refs":["eclipse-psma"]}],"pipeline":["ac225-psma","xaluritamig","mevrometostat","lu177-psma-it","pasritamig","opevesostat","saruparib","bms-986365","fpi-2265","ifinatamab-deruxtecan","hs-20093"],"openProblems":["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."],"parent":"prostate"},"route":"/cancers/prostate-mcrpc/","neighbours":{"drug":[{"id":"lu177-psma-it","kind":"drug","name":"177Lu-PSMA-I&T","route":"/drugs/lu177-psma-it/"},{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","route":"/drugs/ac225-psma/"},{"id":"bms-986365","kind":"drug","name":"BMS-986365","route":"/drugs/bms-986365/"},{"id":"cabazitaxel","kind":"drug","name":"Cabazitaxel","route":"/drugs/cabazitaxel/"},{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"fpi-2265","kind":"drug","name":"FPI-2265","route":"/drugs/fpi-2265/"},{"id":"hs-20093","kind":"drug","name":"HS-20093","route":"/drugs/hs-20093/"},{"id":"ifinatamab-deruxtecan","kind":"drug","name":"Ifinatamab deruxtecan","route":"/drugs/ifinatamab-deruxtecan/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"},{"id":"mevrometostat","kind":"drug","name":"Mevrometostat","route":"/drugs/mevrometostat/"},{"id":"niraparib","kind":"drug","name":"Niraparib","route":"/drugs/niraparib/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"opevesostat","kind":"drug","name":"Opevesostat","route":"/drugs/opevesostat/"},{"id":"pasritamig","kind":"drug","name":"Pasritamig","route":"/drugs/pasritamig/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"},{"id":"rucaparib","kind":"drug","name":"Rucaparib","route":"/drugs/rucaparib/"},{"id":"saruparib","kind":"drug","name":"Saruparib","route":"/drugs/saruparib/"},{"id":"sipuleucel-t","kind":"drug","name":"Sipuleucel-T","route":"/drugs/sipuleucel-t/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"},{"id":"xaluritamig","kind":"drug","name":"Xaluritamig","route":"/drugs/xaluritamig/"},{"id":"zoledronic-acid","kind":"drug","name":"Zoledronic acid","route":"/drugs/zoledronic-acid/"}],"trial":[{"id":"alphabreak","kind":"trial","name":"AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","route":"/trials/alphabreak/"},{"id":"alsympca","kind":"trial","name":"ALSYMPCA","route":"/trials/alsympca/"},{"id":"eclipse-psma","kind":"trial","name":"ECLIPSE","route":"/trials/eclipse-psma/"},{"id":"magnitude","kind":"trial","name":"MAGNITUDE","route":"/trials/magnitude/"},{"id":"mevpro-1","kind":"trial","name":"MEVPRO-1","route":"/trials/mevpro-1/"},{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"},{"id":"propel","kind":"trial","name":"PROpel","route":"/trials/propel/"},{"id":"psmafore","kind":"trial","name":"PSMAfore","route":"/trials/psmafore/"},{"id":"splash","kind":"trial","name":"SPLASH","route":"/trials/splash/"},{"id":"talapro-2","kind":"trial","name":"TALAPRO-2","route":"/trials/talapro-2/"},{"id":"therap","kind":"trial","name":"TheraP (ANZUP 1603)","route":"/trials/therap/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"},{"id":"xalute","kind":"trial","name":"XALute","route":"/trials/xalute/"}],"technology":[{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}],"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}]}}