{"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)","Hormone-relapsed metastatic prostate cancer","Hormone-refractory prostate cancer"],"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":"2026-09-25","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"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":["subtype-page"],"related":["prostate-mhspc","prostate-nmcrpc","prostate-nepc","prostate-bcr"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["brca-reversion-mutations","tnm-prostate-cancer","castration-resistance","radiographic-progression-free-survival","bipolar-androgen-therapy","genome-wide-loss-of-heterozygosity","neuroendocrine-differentiation","chromoplexy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-nejm-2021","paper-profound-nejm-2020","paper-cou-aa-301-abiraterone-de-bono-nejm-2011","paper-alsympca-radium-223-nejm-2013"],"journals":[],"dependsOn":[],"notes":["NICE calls this hormone-relapsed metastatic prostate cancer, which is the heading its own recommendations use; castration-resistant is the term of the trials, the labels and the American guidelines. A British patient will meet both words for the same disease."],"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":{"cancer":[{"id":"prostate-bcr","kind":"cancer","name":"Biochemical recurrence of prostate cancer","route":"/cancers/prostate-bcr/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate-nepc","kind":"cancer","name":"Neuroendocrine and small-cell prostate cancer","route":"/cancers/prostate-nepc/"},{"id":"prostate-nmcrpc","kind":"cancer","name":"Non-metastatic castration-resistant prostate cancer","route":"/cancers/prostate-nmcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"term":[{"id":"ar-v7","kind":"term","name":"AR-V7 splice variant","route":"/terms/ar-v7/"},{"id":"bipolar-androgen-therapy","kind":"term","name":"Bipolar androgen therapy (BAT)","route":"/terms/bipolar-androgen-therapy/"},{"id":"brca-reversion-mutations","kind":"term","name":"BRCA reversion mutations","route":"/terms/brca-reversion-mutations/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"chromoplexy","kind":"term","name":"Chromoplexy","route":"/terms/chromoplexy/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"genome-wide-loss-of-heterozygosity","kind":"term","name":"Genome-wide loss of heterozygosity (gLOH)","route":"/terms/genome-wide-loss-of-heterozygosity/"},{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"neuroendocrine-differentiation","kind":"term","name":"Neuroendocrine differentiation in prostate cancer","route":"/terms/neuroendocrine-differentiation/"},{"id":"prostate-uk-drug-approvals","kind":"term","name":"Prostate cancer drugs in England: what NICE recommends, and what it refuses","route":"/terms/prostate-uk-drug-approvals/"},{"id":"prostate-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","route":"/terms/prostate-failed-programmes/"},{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","route":"/terms/psa-kinetics/"},{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"},{"id":"radiographic-progression-free-survival","kind":"term","name":"Radiographic progression-free survival 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