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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBlood clot (tamoxifen and others)
A swollen painful calf, or sudden breathlessness with chest pain; the tamoxifen boxed warning covers pulmonary embolism and stroke.
- Check before combiningDarolutamide with Apalutamide: major interaction
CYP3A4: Apalutamide (strong inducer) lowers Darolutamide exposure and may cause loss of efficacy.. Avoid combined P-gp and strong CYP3A4 inducers.
- Check before combiningDarolutamide with Enzalutamide: major interaction
CYP3A4: Enzalutamide (strong inducer) lowers Darolutamide exposure and may cause loss of efficacy.. Avoid combined P-gp and strong CYP3A4 inducers.
- Check before combiningEnzalutamide with Apalutamide: major interaction
CYP3A4: Apalutamide (strong inducer) lowers Enzalutamide exposure and may cause loss of efficacy.. Strong inducers lower enzalutamide exposure; avoid or increase to 240 mg.
- Check before combiningFood and drink: Darolutamide
Take with food (exposure roughly doubles).
- Check before combiningFood and drink: Enzalutamide
Seizure risk: caution with drugs that lower the seizure threshold.
See all on the product pages:ApalutamideBicalutamideDarolutamideEnzalutamide·Printable cards in the navigator
Anatomy and lymph node drainage
- Peripheral zone (most cancers)
- Transition zone (BPH)
- Ducts (ductal, intraductal, neuroendocrine)
- Seminal vesicle (T3b)
- Nodes: obturator
- Nodes: internal iliac
- Nodes: external iliac
- Nodes: presacral
About three quarters of cancers 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 cancers)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, very low and low risk, Localised prostate cancer, intermediate risk, 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.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
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 cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 8 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.
- 2020MilestoneApalutamideAll three trials report longer overall survival
A milestone in how this cancer is treated.
- 2019ApprovalDarolutamideDarolutamide approved in US
Non-metastatic CRPC
- 2019MilestoneDarolutamideARAMIS: darolutamide approved for nmCRPC
A milestone in how this cancer is treated.
- 2018ApprovalApalutamideApalutamide approved in US
Non-metastatic CRPC (SPARTAN)
- 2018ApprovalEnzalutamideEnzalutamide approved in US
Non-metastatic CRPC
What is in development for Non-metastatic castration-resistant prostate cancer, drawn from the whole corpus: 0 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.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
Whether PSMA PET-detected metastases should be treated locally or the man treated as metastatic.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- ApalutamideApproved
- PSMA PETStandard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
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
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
Melbourne · cancer center | Australia | none recorded | 0 | 1,547 | 24,196 | #14 | |
Munich · university | Germany | none recorded | 0 | 1,937 | 23,450 | #31 | |
San Francisco · cancer center | United States | 0 | 2,800 | 46,704 | #33 | ||
Los Angeles · cancer center | United States | 0 | 2,019 | 32,934 | - | ||
| Netherlands | 0 | 1,163 | 11,871 | - | |||
New Delhi · hospital | India | none recorded | 0 | 880 | 5,143 | - | |
Düsseldorf · hospital | Germany | none recorded | 0 | 686 | 7,181 | - | |
Freiburg im Breisgau · cancer center | Germany | none recorded | 0 | 549 | 5,261 | - | |
Bern · hospital Programme: Prostate cancer genomics | Switzerland | none recorded | 0 | 470 | 4,598 | - | |
Munich · university | Germany | none recorded | 0 | 438 | 4,021 | - | |
Chandigarh · hospital | India | none recorded | 0 | 398 | 3,509 | - | |
Turku · hospital Programme: Prostate and breast cancer research | Finland | 0 | 227 | 2,451 | - | ||
Bangkok · cancer center | Thailand | none recorded | 0 | 61 | 907 | - | |
Chicago, IL · cancer center | United States | 0 | 43 | 2,105 | - | ||
Newcastle, NSW · consortium Programme: Prostate radiotherapy and androgen deprivation (TROG 96.01, RADAR) | Australia | none recorded | 0 | 34 | 760 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Non-metastatic castration-resistant prostate cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Non-metastatic castration-resistant prostate cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Castrate testosterone, PSA doubling time, Conventional imaging negative, PSMA PET, AR alterations and AR-V7), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include High-risk nmCRPC, Low-risk nmCRPC, PSMA PET-positive, conventional imaging-negative castration-resistant disease.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
High-risk nmCRPC (doubling time 10 months or less)
- For my situation (high-risk nmcrpc (doubling time 10 months or less)), which of the standard options do you recommend and why?Why: Guideline options include: Continue androgen deprivation and add apalutamide (SPARTAN), enzalutamide (PROSPER) or darolutamide (ARAMIS); darolutamide preferred when falls or cognition are concerns.
- Am I a candidate for Apalutamide, Enzalutamide, Darolutamide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Low-risk nmCRPC
- For my situation (low-risk nmcrpc), which of the standard options do you recommend and why?Why: Guideline options include: Observation on androgen deprivation with PSA monitoring and imaging; first-generation antiandrogen or its withdrawal as older options.
- Am I a candidate for Bicalutamide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Staging
- For my situation (staging), which of the standard options do you recommend and why?Why: Guideline options include: PSMA PET locates disease in most men; conventional imaging still defines the setting the trials studied.
Any stage
- Are there clinical trials I could join, for example of Darolutamide, PSMA PET, AR-V7 splice variant?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether PSMA PET-detected metastases should be treated locally or the man treated as metastatic”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Cost and side effects of years of androgen receptor inhibition in men without symptoms”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Non-metastatic castration-resistant prostate cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
2targets
1drugs
4companies
6terms
4Latest papers
topQuery for this cancer: (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- CancerBiochemical recurrence of prostate cancer
Shares Bicalutamide, PSA (prostate-specific antigen), Androgen deprivation & AR pathway inhibitors, Enzalutamide and the tag subtype-page.
- CancerMetastatic hormone-sensitive prostate cancer
Shares Darolutamide, Apalutamide, Androgen deprivation & AR pathway inhibitors, Enzalutamide and the tag subtype-page.
- CancerLocalised prostate cancer, high and very high risk
Shares PSA (prostate-specific antigen), Androgen deprivation & AR pathway inhibitors, PSMA PET, Prostate cancer and the tag subtype-page.
- CancerNeuroendocrine and small-cell prostate cancer
Shares Castration-resistant prostate cancer (CRPC), Androgen deprivation & AR pathway inhibitors, PSMA PET, Prostate cancer and the tag subtype-page.
- CancerLocalised prostate cancer, very low and low risk
Shares PSA (prostate-specific antigen), Prostate cancer and the tag subtype-page.
- CancerLocalised prostate cancer, intermediate risk
Shares Androgen deprivation & AR pathway inhibitors, Prostate cancer and the tag subtype-page.
- CancerMetastatic castration-resistant prostate cancer
Shares Enzalutamide, Prostate cancer and the tag subtype-page.
- TermAndrogen receptor pathway inhibitor (ARPI)
Shares Bicalutamide, Castration-resistant prostate cancer (CRPC), mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer), Enzalutamide.