# Non-metastatic castration-resistant prostate cancer

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

## TL;DR

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-25
- Also known as: nmCRPC; M0 CRPC; Non-metastatic CRPC; Rising PSA on hormone therapy without metastases; Non-metastatic hormone-relapsed prostate cancer
- Tags: subtype-page
- 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/prostate-nmcrpc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/prostate-nmcrpc/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/prostate-nmcrpc/#what-it-is [3 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/prostate-nmcrpc/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/prostate-nmcrpc/#treating-it [3 settings, 2 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/prostate-nmcrpc/#evidence [3 trials, 3 key papers, 4 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/prostate-nmcrpc/#science [1 target]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/prostate-nmcrpc/where-you-are/ [26 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/prostate-nmcrpc/#living-with-it [14 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/prostate-nmcrpc/coming/ [4 medicines, 3 trials, 2 ideas, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/prostate-nmcrpc/data/ [35 connected records, 1 note]

## Standard of care

- High-risk nmCRPC (doubling time 10 months or less): Continue androgen deprivation and add apalutamide (SPARTAN), enzalutamide (PROSPER) or darolutamide (ARAMIS); darolutamide preferred when falls or cognition are concerns. ([Apalutamide](https://onco.cc/drugs/apalutamide/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Darolutamide](https://onco.cc/drugs/darolutamide/), [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/))
- Low-risk nmCRPC: Observation on androgen deprivation with PSA monitoring and imaging; first-generation antiandrogen or its withdrawal as older options. ([Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Bicalutamide](https://onco.cc/drugs/bicalutamide/), [PSA (prostate-specific antigen)](https://onco.cc/terms/psa/))
- Staging: PSMA PET locates disease in most men; conventional imaging still defines the setting the trials studied. ([PSMA PET](https://onco.cc/technologies/psma-pet/), [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://onco.cc/terms/mcrpc-mhspc/))

## State of the art

- 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.

## Open problems

- 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.

## 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.

## 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
- 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: [Biochemical recurrence of prostate cancer](https://onco.cc/cancers/prostate-bcr/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Neuroendocrine and small-cell prostate cancer](https://onco.cc/cancers/prostate-nepc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- terms: [AR-V7 splice variant](https://onco.cc/terms/ar-v7/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Disease volume (CHAARTED high-volume versus low-volume) and LATITUDE risk](https://onco.cc/terms/disease-volume-chaarted/), [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/), [Other-cause mortality](https://onco.cc/terms/other-cause-mortality/), [Prostate cancer drugs in England: what NICE recommends, and what it refuses](https://onco.cc/terms/prostate-uk-drug-approvals/), [PSA (prostate-specific antigen)](https://onco.cc/terms/psa/), [PSA doubling time](https://onco.cc/terms/psa-doubling-time/), [PSA kinetics: PSA doubling time and PSA density](https://onco.cc/terms/psa-kinetics/), [PTEN loss](https://onco.cc/terms/pten-loss/), [TNM staging for prostate cancer, and what changed in the 9th edition](https://onco.cc/terms/tnm-prostate-cancer/), [What androgen deprivation costs: the side of hormone therapy the survival curves do not show](https://onco.cc/terms/prostate-adt-burden/)
- trials: [A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer](https://onco.cc/trials/nct01946204/), [ARAMIS](https://onco.cc/trials/aramis/), [PROSPER](https://onco.cc/trials/prosper/)
- key papers: [ARAMIS: darolutamide in non-metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-aramis-nejm-2019/), [PROSPER: enzalutamide in men with non-metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-prosper-nejm-2018/), [SPARTAN: apalutamide for non-metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-spartan-nejm-2018/)
- drugs: [Apalutamide](https://onco.cc/drugs/apalutamide/), [Bicalutamide](https://onco.cc/drugs/bicalutamide/), [Darolutamide](https://onco.cc/drugs/darolutamide/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/)
- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [PSMA PET](https://onco.cc/technologies/psma-pet/)
- roadmaps: [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](https://onco.cc/roadmaps/prostate-roadmap/)
- ideas: [Report death from other causes as an outcome of the prostate cancer service, split by deprivation and ethnicity](https://onco.cc/ideas/idea-prostate-other-cause-mortality-as-a-reported-service-outcome/), [Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later](https://onco.cc/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/)

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