# Castration-resistant prostate cancer (CRPC)

Source: https://onco.cc/terms/castration-resistance/  
OnCo record `castration-resistance` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Prostate cancer that keeps growing even though testosterone has been reduced to castrate levels.

## Summary

Defined by PSA or radiographic progression with testosterone <50 ng/dL. Mechanisms: AR amplification and mutations, AR-V7 splice variants, intratumoural androgen synthesis, glucocorticoid receptor bypass, lineage plasticity to neuroendocrine phenotype. Since 2026 the FDA label language 'androgen pathway modulation-naive or -sensitive' replaces 'hormone-sensitive'.

## Fields

- Kind: Term
- Last checked: 2026-09-06
- Also known as: hormone-relapsed prostate cancer; hormone-relapsed; hormone relapsed; hormone-refractory prostate cancer

## Notes

- The NHS calls it something else. NICE NG131 does not use the phrase castration-resistant anywhere in its recommendations; its section is headed 'hormone-relapsed metastatic prostate cancer' and its advice on docetaxel, on genomic biomarker-based treatment and on zoledronic acid is written in those words. Castration-resistant, castration-sensitive, mCRPC and mHSPC are the words of the trials, the drug labels and the American guidelines. They mean the same thing, and a British patient may meet both in the same week from different people.
- Read molecularly, castration resistance is androgen receptor reactivation by one of five routes: amplification of the gene (about half of castration-resistant cohorts against 1% of primaries), amplification of an enhancer 624 kb upstream (81% of 101 deeply sequenced metastases), ligand-binding-domain mutation (13.7 to 18.0%), splicing out the ligand-binding domain (AR-V7), and simply raising receptor expression with no genomic change. The exits from receptor dependence, neuroendocrine transformation and the androgen receptor-null, neuroendocrine-null state, are the minority.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer
- NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15): https://www.nice.org.uk/guidance/ng131/chapter/Recommendations

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Neuroendocrine and small-cell prostate cancer](https://onco.cc/cancers/prostate-nepc/), [Non-metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-nmcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/)
- terms: [Androgen deprivation therapy (ADT)](https://onco.cc/terms/adt/), [Androgen receptor pathway inhibitor (ARPI)](https://onco.cc/terms/arpi/), [AR-V7 splice variant](https://onco.cc/terms/ar-v7/), [Bipolar androgen therapy (BAT)](https://onco.cc/terms/bipolar-androgen-therapy/), [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://onco.cc/terms/mcrpc-mhspc/), [Metastasis-free survival (MFS)](https://onco.cc/terms/metastasis-free-survival/), [Neuroendocrine differentiation in prostate cancer](https://onco.cc/terms/neuroendocrine-differentiation/), [Orchiectomy](https://onco.cc/terms/orchiectomy/), [Prostate cancer drugs in England: what NICE recommends, and what it refuses](https://onco.cc/terms/prostate-uk-drug-approvals/), [Prostate cancer programmes that failed, and what each failure taught](https://onco.cc/terms/prostate-failed-programmes/), [PSA kinetics: PSA doubling time and PSA density](https://onco.cc/terms/psa-kinetics/), [Radiographic progression-free survival (rPFS)](https://onco.cc/terms/radiographic-progression-free-survival/), [Time to progression (TTP) and time to next treatment (TTNT)](https://onco.cc/terms/ttp/), [TNM staging for prostate cancer, and what changed in the 9th edition](https://onco.cc/terms/tnm-prostate-cancer/), [What follows what in castration-resistant prostate cancer](https://onco.cc/terms/prostate-crpc-sequencing/), [Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters](https://onco.cc/terms/prostate-hrr-eligibility/)
- key papers: [Abiraterone in metastatic prostate cancer without previous chemotherapy](https://onco.cc/key-papers/paper-abiraterone-acetate-prostate-n-engl-j-med-2013/), [AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy](https://onco.cc/key-papers/paper-scher-affirm-enzalutamide-nejm-2012/), [Androgen receptor pathway-independent prostate cancer is sustained through FGF signalling](https://onco.cc/key-papers/paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017/), [AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer](https://onco.cc/key-papers/paper-antonarakis-ar-v7-resistance-nejm-2014/), [Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer](https://onco.cc/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/), [Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers](https://onco.cc/key-papers/paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016/), [Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer](https://onco.cc/key-papers/paper-beltran-nepc-divergent-evolution-nat-med-2016/), [Genomic correlates of clinical outcome in advanced prostate cancer](https://onco.cc/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/), [Genomic hallmarks and structural variation in metastatic prostate cancer](https://onco.cc/key-papers/paper-quigley-structural-variation-mcrpc-cell-2018/), [Genomics of lethal prostate cancer at diagnosis and castration resistance](https://onco.cc/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/), [Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate](https://onco.cc/key-papers/paper-huggins-hodges-castration-serum-phosphatases-prostate-1941/), [In vivo amplification of the androgen receptor gene and progression of human prostate cancer](https://onco.cc/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/), [IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/), [Molecular determinants of resistance to antiandrogen therapy](https://onco.cc/key-papers/paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004/), [Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-labrecque-mcrpc-phenotypes-jci-2019/), [Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer](https://onco.cc/key-papers/paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995/), [Nuclear-localised androgen receptor splice variant 7 in circulating tumour cells as a predictive biomarker in castration-resistant prostate cancer](https://onco.cc/key-papers/paper-scher-nuclear-arv7-taxane-vs-arsi-jama-oncol-2018/), [Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer](https://onco.cc/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/), [Phase 1 trial of abiraterone acetate confirms that castration-resistant prostate cancer commonly remains hormone driven](https://onco.cc/key-papers/paper-attard-abiraterone-phase-1-cyp17-jco-2008/), [PREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy](https://onco.cc/key-papers/paper-beer-prevail-enzalutamide-nejm-2014/), [PROPHECY: prospective multicentre validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer](https://onco.cc/key-papers/paper-prophecy-arv7-validation-jco-2019/), [Proposed morphologic classification of prostate cancer with neuroendocrine differentiation](https://onco.cc/key-papers/paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014/), [PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate](https://onco.cc/key-papers/paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015/), [Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance](https://onco.cc/key-papers/paper-ku-rb1-trp53-lineage-plasticity-science-2017/), [Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer](https://onco.cc/key-papers/paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011/), [RESTORE: bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018/), [SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer](https://onco.cc/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer](https://onco.cc/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/), [SWOG 9916: docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer](https://onco.cc/key-papers/paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004/), [TAX 327: docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer](https://onco.cc/key-papers/paper-tannock-tax-327-docetaxel-prednisone-nejm-2004/), [The mutational landscape of lethal castration-resistant prostate cancer](https://onco.cc/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/), [TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/), [TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel](https://onco.cc/key-papers/paper-de-bono-tropic-cabazitaxel-lancet-2010/)
- trials: [10TASQ10](https://onco.cc/trials/tasquinimod-10tasq10/), [AFFINITY](https://onco.cc/trials/affinity-custirsen/), [AFFIRM](https://onco.cc/trials/affirm/), [ARMOR3-SV](https://onco.cc/trials/armor3-sv/), [CA184-043](https://onco.cc/trials/ca184-043-ipilimumab/), [CALGB 90401](https://onco.cc/trials/calgb-90401/), [CARD](https://onco.cc/trials/card/), [COMET-1](https://onco.cc/trials/comet-1/), [COU-AA-301](https://onco.cc/trials/cou-aa-301/), [COU-AA-302](https://onco.cc/trials/cou-aa-302/), [ELM-PC 4](https://onco.cc/trials/elm-pc-4-orteronel/), [ENTHUSE M1](https://onco.cc/trials/enthuse-m1-zibotentan/), [ERA 223](https://onco.cc/trials/era-223/), [FIRSTANA](https://onco.cc/trials/firstana/), [HERO](https://onco.cc/trials/hero/), [IMbassador250](https://onco.cc/trials/imbassador250/), [IMPACT (sipuleucel-T)](https://onco.cc/trials/impact-sipuleucel-t/), [KEYNOTE-641](https://onco.cc/trials/keynote-641/), [KEYNOTE-921](https://onco.cc/trials/keynote-921/), [PEACE-3 (EORTC 1333)](https://onco.cc/trials/peace-3/), [PREVAIL](https://onco.cc/trials/prevail/), [PROSELICA](https://onco.cc/trials/proselica/), [PROSPECT](https://onco.cc/trials/prospect-prostvac/), [PSMAddition](https://onco.cc/trials/psmaddition/), [READY](https://onco.cc/trials/ready-dasatinib/), [SWOG 9916](https://onco.cc/trials/swog-9916/), [SWOG S0421](https://onco.cc/trials/swog-s0421-atrasentan/), [SYNERGY](https://onco.cc/trials/synergy-custirsen/), [TAX 327](https://onco.cc/trials/tax-327/), [TRITON3](https://onco.cc/trials/triton3/), [TROPIC](https://onco.cc/trials/tropic/)
- ideas: [Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint](https://onco.cc/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/), [Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it](https://onco.cc/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/)
- drugs: [Atrasentan](https://onco.cc/drugs/atrasentan/), [Custirsen](https://onco.cc/drugs/custirsen/), [Galeterone](https://onco.cc/drugs/galeterone/), [Leuprolide (leuprorelin) and GnRH agonists](https://onco.cc/drugs/leuprolide/), [Orteronel](https://onco.cc/drugs/orteronel/), [PROSTVAC](https://onco.cc/drugs/prostvac/), [Tasquinimod](https://onco.cc/drugs/tasquinimod/), [Zibotentan](https://onco.cc/drugs/zibotentan/)
- biomarkers: [AR amplification (gene and upstream enhancer)](https://onco.cc/biomarkers/ar-amplification/), [AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)](https://onco.cc/biomarkers/ar-ligand-binding-domain-mutation/), [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/), [SPOP mutation](https://onco.cc/biomarkers/spop-mutation/), [Treatment-emergent neuroendocrine transformation (recognising it)](https://onco.cc/biomarkers/nepc-transformation/)
- targets: [CYP17A1 (17-alpha-hydroxylase/17,20-lyase)](https://onco.cc/targets/cyp17a1/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/)
- collections: [Prostate Cancer Foundation (PCF)](https://onco.cc/collections/prostate-cancer-foundation/)

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JSON: https://onco.cc/api/v1/entities/castration-resistance.json