{"entity":{"id":"prostate-nmcrpc","kind":"cancer","name":"Non-metastatic castration-resistant prostate cancer","aka":["nmCRPC","M0 CRPC","Non-metastatic CRPC","Rising PSA on hormone therapy without metastases","Non-metastatic hormone-relapsed prostate cancer"],"tldr":"Non-metastatic castration-resistant prostate cancer is a PSA that keeps rising on hormone therapy while scans still show nothing. Three androgen receptor blockers, apalutamide, enzalutamide and darolutamide, each delay metastasis by about two years and lengthen life, and darolutamide is the gentlest.","summary":"Non-metastatic castration-resistant prostate cancer is defined by a rising PSA with castrate testosterone (below 50 ng/dL) and no metastases on CT and bone scan. It is found in men on long-term androgen deprivation, and the risk is judged by PSA doubling time: under ten months marks high risk. Three trials in men with a doubling time of ten months or less changed care in 2018 and 2019: SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide) each roughly doubled metastasis-free survival, from about 16 to 18 months to 36 to 40 months, and each later showed longer overall survival, so all three are approved. Darolutamide crosses into the brain least and causes the fewest falls, fractures and cognitive effects. Men with a slow doubling time can be observed on hormone therapy. PSMA PET now finds metastases in most of these men, which moves them into metastatic castration-resistant disease on paper without changing their biology, so guidelines still treat by the conventional imaging that the trials used.","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-bcr","prostate-mhspc","prostate-mcrpc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa-kinetics","disease-volume-chaarted","pten-loss","tnm-prostate-cancer","castration-resistance","metastasis-free-survival","other-cause-mortality","psa-doubling-time"],"trials":["aramis","nct01946204","prosper"],"people":[],"bottlenecks":[],"keyPapers":["paper-spartan-nejm-2018","paper-prosper-nejm-2018","paper-aramis-nejm-2019"],"journals":[],"dependsOn":[],"notes":["NICE calls this hormone-relapsed rather than castration-resistant. NG131's section is headed 'hormone-relapsed metastatic prostate cancer' and the phrase castration-resistant does not appear in its recommendations, while the trials, the drug labels and the American guidelines use castration-resistant throughout. They describe the same state."],"group":"genitourinary","burden":"A shrinking group, because PSMA PET reveals metastases in most men once called non-metastatic; about a third with a PSA doubling time under ten months developed visible metastases within two years on hormone therapy alone.","subtypes":["High-risk nmCRPC (PSA doubling time 10 months or less)","Low-risk nmCRPC (slow PSA doubling time, observation)","PSMA PET-positive, conventional imaging-negative castration-resistant disease"],"biomarkers":["Castrate testosterone (below 50 ng/dL)","PSA doubling time","Conventional imaging negative","PSMA PET (often positive)","AR alterations and AR-V7 (research)"],"standardOfCare":[{"setting":"High-risk nmCRPC (doubling time 10 months or less)","approach":"Continue androgen deprivation and add apalutamide (SPARTAN), enzalutamide (PROSPER) or darolutamide (ARAMIS); darolutamide preferred when falls or cognition are concerns.","refs":["apalutamide","enzalutamide","darolutamide","androgen-deprivation","castration-resistance"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Low-risk nmCRPC","approach":"Observation on androgen deprivation with PSA monitoring and imaging; first-generation antiandrogen or its withdrawal as older options.","refs":["androgen-deprivation","bicalutamide","psa"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Staging","approach":"PSMA PET locates disease in most men; conventional imaging still defines the setting the trials studied.","refs":["psma-pet","mcrpc-mhspc"]}],"stateOfArt":["Three androgen receptor inhibitors, each proven in its own trial, give men a choice weighted by side effects.","Metastasis-free survival was accepted by regulators as a surrogate endpoint on the strength of these trials.","PSMA PET is dissolving the category from the inside."],"history":[{"year":2012,"title":"Metastasis-free survival validated as a surrogate for survival in prostate cancer","refs":["castration-resistance"]},{"year":2018,"title":"SPARTAN and PROSPER: apalutamide and enzalutamide approved for nmCRPC","refs":["apalutamide","enzalutamide"]},{"year":2019,"title":"ARAMIS: darolutamide approved for nmCRPC","refs":["darolutamide"]},{"year":2020,"title":"All three trials report longer overall survival","refs":["apalutamide","enzalutamide","darolutamide"]}],"pipeline":["darolutamide","psma-pet","ar-v7"],"openProblems":["Whether PSMA PET-detected metastases should be treated locally or the man treated as metastatic.","Cost and side effects of years of androgen receptor inhibition in men without symptoms.","No trial compares the three drugs head to head."],"parent":"prostate"},"route":"/cancers/prostate-nmcrpc/","neighbours":{"cancer":[{"id":"prostate-bcr","kind":"cancer","name":"Biochemical recurrence of prostate cancer","route":"/cancers/prostate-bcr/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"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","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"term":[{"id":"ar-v7","kind":"term","name":"AR-V7 splice variant","route":"/terms/ar-v7/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"disease-volume-chaarted","kind":"term","name":"Disease volume (CHAARTED high-volume versus low-volume) and LATITUDE risk","route":"/terms/disease-volume-chaarted/"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"},{"id":"metastasis-free-survival","kind":"term","name":"Metastasis-free survival (MFS)","route":"/terms/metastasis-free-survival/"},{"id":"other-cause-mortality","kind":"term","name":"Other-cause mortality","route":"/terms/other-cause-mortality/"},{"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":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"},{"id":"psa-doubling-time","kind":"term","name":"PSA doubling time","route":"/terms/psa-doubling-time/"},{"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":"tnm-prostate-cancer","kind":"term","name":"TNM staging for prostate cancer, and what changed in the 9th edition","route":"/terms/tnm-prostate-cancer/"},{"id":"prostate-adt-burden","kind":"term","name":"What androgen deprivation costs: the side of hormone therapy the survival curves do not show","route":"/terms/prostate-adt-burden/"}],"trial":[{"id":"nct01946204","kind":"trial","name":"A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer","route":"/trials/nct01946204/"},{"id":"aramis","kind":"trial","name":"ARAMIS","route":"/trials/aramis/"},{"id":"prosper","kind":"trial","name":"PROSPER","route":"/trials/prosper/"}],"paper":[{"id":"paper-aramis-nejm-2019","kind":"paper","name":"ARAMIS: darolutamide in non-metastatic castration-resistant prostate cancer","route":"/key-papers/paper-aramis-nejm-2019/"},{"id":"paper-prosper-nejm-2018","kind":"paper","name":"PROSPER: enzalutamide in men with non-metastatic castration-resistant prostate cancer","route":"/key-papers/paper-prosper-nejm-2018/"},{"id":"paper-spartan-nejm-2018","kind":"paper","name":"SPARTAN: apalutamide for non-metastatic castration-resistant prostate cancer","route":"/key-papers/paper-spartan-nejm-2018/"}],"drug":[{"id":"apalutamide","kind":"drug","name":"Apalutamide","route":"/drugs/apalutamide/"},{"id":"bicalutamide","kind":"drug","name":"Bicalutamide","route":"/drugs/bicalutamide/"},{"id":"darolutamide","kind":"drug","name":"Darolutamide","route":"/drugs/darolutamide/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"}],"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"idea":[{"id":"idea-prostate-other-cause-mortality-as-a-reported-service-outcome","kind":"idea","name":"Report death from other causes as an outcome of the prostate cancer service, split by deprivation and ethnicity","route":"/ideas/idea-prostate-other-cause-mortality-as-a-reported-service-outcome/"},{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","route":"/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/"}]}}