Non-metastatic castration-resistant prostate cancer
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.
Overview
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.
State of the art
- Three androgen receptor inhibitors, each proven in its own trial, give men a choice weighted by side effects.
- PSMA PET is dissolving the category from the inside.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Metastasis-free survival was accepted by regulators as a surrogate endpoint on the strength of these trials.
Anatomy and lymph node drainage
- Peripheral zone (most indications)
- Transition zone (BPH)
- Ducts (ductal, intraductal, neuroendocrine)
- Seminal vesicle (T3b)
- Nodes: obturator
- Nodes: internal iliac
- Nodes: external iliac
- Nodes: presacral
About three quarters of indications arise in the peripheral zone at the back of the gland, the part a finger or a biopsy needle reaches; drainage is to the obturator and iliac nodes.
- Peripheral zone (most indications)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
- Transition zone (BPH)
- Ducts (ductal, intraductal, neuroendocrine)
- Seminal vesicle (T3b)
- obturator
- internal iliac
- external iliac
- presacral
Same organ: Prostate cancer, Localised prostate cancer, high and very high risk, Biochemical recurrence of prostate cancer, Metastatic hormone-sensitive prostate cancer, Metastatic castration-resistant prostate cancer, Neuroendocrine and small-cell prostate cancer
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.
Continue androgen deprivation and add apalutamide (SPARTAN), enzalutamide (PROSPER) or darolutamide (ARAMIS); darolutamide preferred when falls or cognition are concerns.
Observation on androgen deprivation with PSA monitoring and imaging; first-generation antiandrogen or its withdrawal as older options.
PSMA PET locates disease in most men; conventional imaging still defines the setting the trials studied.
Subtypes & biomarkers
top- 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
- Castrate testosterone (below 50 ng/dL)
- PSA doubling time
- Conventional imaging negative
- PSMA PET (often positive)
- AR alterations and AR-V7 (research)
How often this target appears
- 2012Metastasis-free survival validated as a surrogate for survival in prostate cancer
- 2018SPARTAN and PROSPER: apalutamide and enzalutamide approved for nmCRPC
- 2019ARAMIS: darolutamide approved for nmCRPC
- 2020All three trials report longer overall survival
Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 7 changes by month →- 2026-09-17This recordNon-metastatic castration-resistant prostate cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2020MilestoneEnzalutamideAll three trials report longer overall survival
A milestone in how this cancer is treated.
- 2019MilestoneNon-metastatic castration-resistant prostate cancerARAMIS: darolutamide approved for nmCRPC
A milestone in how this cancer is treated.
- 2018ApprovalEnzalutamideEnzalutamide approved in US
Non-metastatic CRPC
- 2018Trial resultPROSPERPROSPER reported
Enzalutamide lengthened metastasis-free survival and, with longer follow-up, overall survival compared with placebo; approved in July 2018.
- 2018MilestoneEnzalutamideSPARTAN and PROSPER: apalutamide and enzalutamide approved for nmCRPC
A milestone in how this cancer is treated.
What is in development for Non-metastatic castration-resistant prostate cancer, drawn from the whole corpus: 1 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials reported · 1
- PROSPER · phase 3 · 2018 · positive
Open problems and what is being done
Whether PSMA PET-detected metastases should be treated locally or the man treated as metastatic.
What is being done about thisAdvanced and metastatic diseaseAvailable now- PSMA PETStandard of care
In trials- PROSPERPositive
Ideas and roadmapsNothing recorded yet.
Also on Nuclide: Indications.
Cost and side effects of years of androgen receptor inhibition in men without symptoms.
No trial compares the three drugs head to head.
Trials
topTrials recruiting now
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Landmark trials
Direct links plus the targets, companies, and technologies of this cancer's products.
Latest papers
topQuery for this indication: (TITLE:"Non-metastatic castration-resistant prostate cancer" OR ABSTRACT:"Non-metastatic castration-resistant prostate cancer" OR TITLE:"nmCRPC" OR ABSTRACT:"nmCRPC" OR TITLE:"M0 CRPC" OR ABSTRACT:"M0 CRPC" OR TITLE:"Non-metastatic CRPC" OR ABSTRACT:"Non-metastatic CRPC" OR TITLE:"Rising PSA on hormone therapy without metastases" OR ABSTRACT:"Rising PSA on hormone therapy without metastases") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Non-metastatic castration-resistant prostate cancer, not a curated reading list.
Similar pages
not linked directly; found by shared links- IndicationLocalised prostate cancer, high and very high risk
Shares Metastatic hormone-sensitive prostate cancer, Biochemical recurrence of prostate cancer, PSMA PET, Prostate cancer and the tag subtype-page.
- TermOligometastatic disease
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- TrialSTAMPEDE
Shares mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer), Metastatic hormone-sensitive prostate cancer, Enzalutamide, Prostate cancer.
- TrialEMBARK
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- TermAndrogen receptor pathway inhibitor (ARPI)
Shares mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer), Enzalutamide, Prostate cancer.
- TrialENZA-p
Shares Enzalutamide, Metastatic castration-resistant prostate cancer, PSMA PET.
- CompanyPfizer (incl. Seagen)
Shares PROSPER, Enzalutamide, Prostate cancer.
- TrialA Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA
Shares Enzalutamide, Metastatic castration-resistant prostate cancer, Prostate cancer.