Metastatic castration-resistant prostate cancer
Metastatic castration-resistant prostate cancer is disease that grows despite castrate testosterone. Sequenced treatments now include androgen receptor inhibitors, docetaxel and cabazitaxel, PARP inhibitors for men with BRCA-type mutations, the radioligand 177Lu-PSMA-617 and radium-223 for bone-predominant disease.
Overview
Metastatic castration-resistant prostate cancer is defined by progression on scans or PSA, or new metastases, with castrate testosterone. Nearly every man reaches it from hormone-sensitive disease, and the treatment chosen depends on what he has already had. Men who have not had an androgen receptor pathway inhibitor receive abiraterone or enzalutamide; PROpel, TALAPRO-2 and MAGNITUDE showed that adding olaparib, talazoparib or niraparib helps men with BRCA and other homologous recombination repair mutations, and PROfound showed olaparib alone beats a second hormonal agent in these men. Docetaxel and then cabazitaxel remain the chemotherapies. VISION established 177Lu-PSMA-617 after chemotherapy and PSMAfore moved it before, for PSMA PET-positive disease; 177Lu-PSMA-I&T (SPLASH, ECLIPSE) follows the same path. Radium-223 lengthens life in symptomatic bone-predominant disease without visceral metastases (ALSYMPCA), sipuleucel-T is still approved for minimally symptomatic disease, and pembrolizumab is used for the rare mismatch repair-deficient tumour. Tumour and germline testing for HRR genes and mismatch repair is standard. Actinium-225 PSMA agents, the STEAP1 T-cell engager xaluritamig and the EZH2 inhibitor mevrometostat are in phase 3.
State of the art
- PSMA PET and 177Lu-PSMA-617 make prostate cancer the model for theranostics.
- PARP inhibitors gave prostate cancer its first genotype-directed treatment.
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.
- Survival in this once six-month setting is now measured in years, built from sequenced drugs rather than one breakthrough.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBlood clot
A swollen painful calf, or sudden breathlessness with chest pain; venous thromboembolism including pulmonary embolism is a labelled warning.
- Emergency services nowBone pain flare or fracture (radium-223)
Sudden severe bone pain, or back pain with weakness or numbness in the legs (possible spinal cord compression).
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- 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.
- Emergency services nowCytokine release syndrome
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
See all on the product pages:177Lu-PSMA-I&TAbiraterone acetateActinium-225 PSMA agentsCabazitaxelDocetaxelEnzalutamideLutetium-177 vipivotide tetraxetanNiraparibOlaparibPembrolizumabRadium-223 dichlorideRucaparibTalazoparibXaluritamig·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)mCRPC, androgen receptor pathway inhibitor-naive · mCRPC after an androgen receptor pathway inhibitor, chemotherapy-naive · mCRPC after taxane chemotherapy · HRR-mutant mCRPC (BRCA1, BRCA2, ATM and others; PARP inhibitors) · PSMA PET-positive mCRPC (radioligand therapy) · Bone-predominant mCRPC without visceral metastases (radium-223) · Mismatch repair-deficient mCRPC (pembrolizumab)
- 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, Non-metastatic castration-resistant prostate cancer, Neuroendocrine and small-cell prostate cancer
The state in which nearly all prostate cancer deaths occur, about 400,000 a year worldwide; median survival from first treatment is now around three years, longer for men who have not had an androgen receptor inhibitor.
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.
Abiraterone or enzalutamide; add olaparib, talazoparib or niraparib for HRR-mutant, above all BRCA-mutant, disease (PROpel, TALAPRO-2, MAGNITUDE).
Docetaxel; olaparib or rucaparib for BRCA-mutant disease (PROfound); 177Lu-PSMA-617 for PSMA-positive disease before chemotherapy (PSMAfore); pembrolizumab for mismatch repair-deficient tumours.
177Lu-PSMA-617 (VISION), cabazitaxel, radium-223 for symptomatic bone-only disease (ALSYMPCA), or a PARP inhibitor if not yet used.
Denosumab or zoledronic acid to prevent skeletal events, with calcium and vitamin D; palliative radiotherapy to painful metastases.
Actinium-225 PSMA radioligands, the STEAP1 T-cell engager xaluritamig, the EZH2 inhibitor mevrometostat and 177Lu-PSMA-I&T within trials.
Subtypes & biomarkers
top- mCRPC, androgen receptor pathway inhibitor-naive
- mCRPC after an androgen receptor pathway inhibitor, chemotherapy-naive
- mCRPC after taxane chemotherapy
- HRR-mutant mCRPC (BRCA1, BRCA2, ATM and others; PARP inhibitors)
- PSMA PET-positive mCRPC (radioligand therapy)
- Bone-predominant mCRPC without visceral metastases (radium-223)
- Mismatch repair-deficient mCRPC (pembrolizumab)
- Tumour and germline HRR genes (BRCA2 above all)
- PSMA PET uptake and FDG discordance
- Mismatch repair deficiency and tumour mutational burden
- PSA and alkaline phosphatase
- Circulating tumour DNA (AR amplification, BRCA2 reversion)
- AR-V7 in circulating tumour cells (research)
How often this target appears
- 2004TAX 327: docetaxel is the first drug to lengthen life in castration-resistant disease
- 2010Cabazitaxel and sipuleucel-T approved
- 2011Abiraterone approved after docetaxel
- 2012Enzalutamide approved
- 2013ALSYMPCA: radium-223, the first alpha emitter
- 2020PROfound: olaparib for HRR-mutant disease
- 2021VISION: 177Lu-PSMA-617 lengthens life
- 2022PROpel and MAGNITUDE: PARP inhibitor plus abiraterone
- 2023PSMAfore and TALAPRO-2
- 2025ECLIPSE: 177Lu-PSMA-I&T meets its endpoint
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 40 changes by month →- 2026-09-17This recordMetastatic castration-resistant prostate cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2025-03-28RegulatoryLutetium-177 vipivotide tetraxetanLutetium-177 vipivotide tetraxetan: approval (US)
PSMA+ mCRPC after ARPI, before chemotherapy (PSMAfore)
- 2025ApprovalLutetium-177 vipivotide tetraxetanLutetium-177 vipivotide tetraxetan approved in US
PSMA+ mCRPC after ARPI, before chemotherapy
- 2025Trial resultECLIPSEECLIPSE reported
rPFS significantly improved.
- 2025MilestoneECLIPSEECLIPSE: 177Lu-PSMA-I&T meets its endpoint
A milestone in how this cancer is treated.
- 2024Trial resultSPLASHSPLASH reported
rPFS HR 0.
What is in development for Metastatic castration-resistant prostate cancer, drawn from the whole corpus: 26 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.
Drugs in phase 3 · 10
Drugs in phase 2 · 1
Technologies being tested · 2
Trials under way · 3
- AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617) · phase 2 · AstraZeneca (Fusion); Novartis
- MEVPRO-1 · phase 3 · Pfizer
- XALute · phase 3 · Amgen
Trials reported · 10
- ALSYMPCA · phase 3 · 2013 · positive
- ECLIPSE · phase 3 · 2025 · positive
- MAGNITUDE · phase 3 · 2022 · mixed
- PROfound · phase 3 · 2020 · positive
- PROpel · phase 3 · 2022 · positive
- PSMAfore · phase 3 · 2023 · positive
- SPLASH · phase 3 · 2024 · mixed
- TALAPRO-2 · phase 3 · 2023 · positive
- TheraP (ANZUP 1603) · phase 2 · 2021 · positive
- VISION · phase 3 · 2021 · positive
Open problems and what is being done
The best sequence of radioligand, PARP inhibitor and chemotherapy is untested.
Actinium-225 supply and the lack of alpha-emitter dosimetry.
and how the field plans to fix it →What is being done about thisCost and accessAvailable nowNothing recorded yet.
In trials- Actinium-225 PSMA agentsPhase 3
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Financial help · Coverage by country · HTA decisions.
Lineage plasticity to neuroendocrine disease under androgen receptor blockade.
Resistance to 177Lu-PSMA-617 in PSMA-low or FDG-discordant disease.
and how the field plans to fix it →What is being done about thisResistance to treatmentAvailable now- EnzalutamideApproved
- TalazoparibApproved
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Resistance atlas · Lines of therapy.
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.
Landmark trials
Expert centres
topExpert centres
| United Kingdom | none recorded | 0 | 1,026 | 17,745 | #7 | ||
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Melbourne · cancer center | Australia | none recorded | 1 | 1,547 | 24,196 | #14 | |
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
Sydney · consortium | Australia | none recorded | 1 | 3 | 3 | - | |
Essen · cancer center | Germany | none recorded | 1 | not matched | - | - | |
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Ramat Gan · hospital | Israel | none recorded | 0 | 715 | 9,094 | - | |
London · hospital Programme: Prostate and urology | United Kingdom | none recorded | 0 | 693 | 7,168 | - | |
Düsseldorf · hospital | Germany | none recorded | 0 | 686 | 7,181 | - | |
| United Kingdom | none recorded | 0 | 641 | 10,459 | none recorded | - | |
Aarhus · hospital | Denmark | none recorded | 0 | 624 | 4,497 | - |
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 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 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 Tumour and germline HRR genes, PSMA PET uptake and FDG discordance, Mismatch repair deficiency and tumour mutational burden, PSA and alkaline phosphatase, Circulating tumour DNA), 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 mCRPC, androgen receptor pathway inhibitor-naive, mCRPC after an androgen receptor pathway inhibitor, chemotherapy-naive, mCRPC after taxane chemotherapy.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
First line, androgen receptor pathway inhibitor-naive
- For my situation (first line, androgen receptor pathway inhibitor-naive), which of the standard options do you recommend and why?Why: Guideline options include: Abiraterone or enzalutamide; add olaparib, talazoparib or niraparib for HRR-mutant, above all BRCA-mutant, disease (PROpel, TALAPRO-2, MAGNITUDE).
- Am I a candidate for Abiraterone acetate, Enzalutamide, Olaparib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PROpel and TALAPRO-2 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
After an androgen receptor pathway inhibitor
- For my situation (after an androgen receptor pathway inhibitor), which of the standard options do you recommend and why?Why: Guideline options include: Docetaxel; olaparib or rucaparib for BRCA-mutant disease (PROfound); 177Lu-PSMA-617 for PSMA-positive disease before chemotherapy (PSMAfore); pembrolizumab for mismatch repair-deficient tumours.
- Am I a candidate for Docetaxel, Olaparib, Rucaparib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PROfound and PSMAfore apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
After docetaxel
- For my situation (after docetaxel), which of the standard options do you recommend and why?Why: Guideline options include: 177Lu-PSMA-617 (VISION), cabazitaxel, radium-223 for symptomatic bone-only disease (ALSYMPCA), or a PARP inhibitor if not yet used.
- Am I a candidate for Lutetium-177 vipivotide tetraxetan, Cabazitaxel, Radium-223 dichloride, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of VISION and ALSYMPCA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Bone health
- For my situation (bone health), which of the standard options do you recommend and why?Why: Guideline options include: Denosumab or zoledronic acid to prevent skeletal events, with calcium and vitamin D; palliative radiotherapy to painful metastases.
- Am I a candidate for Denosumab, Zoledronic acid, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Phase 3 options
- For my situation (phase 3 options), which of the standard options do you recommend and why?Why: Guideline options include: Actinium-225 PSMA radioligands, the STEAP1 T-cell engager xaluritamig, the EZH2 inhibitor mevrometostat and 177Lu-PSMA-I&T within trials.
- Am I a candidate for Actinium-225 PSMA agents, Xaluritamig, Mevrometostat or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617) and XALute apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Actinium-225 PSMA agents, Xaluritamig, Mevrometostat, 177Lu-PSMA-I&T?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 “The best sequence of radioligand, PARP inhibitor and chemotherapy is untested”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Actinium-225 supply and the lack of alpha-emitter dosimetry”. 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 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
14targets
11drugs
25companies
19trials
13Latest papers
topQuery for this cancer: (TITLE:"Metastatic castration-resistant prostate cancer" OR ABSTRACT:"Metastatic castration-resistant prostate cancer" OR TITLE:"mCRPC" OR ABSTRACT:"mCRPC" OR TITLE:"Metastatic CRPC" OR ABSTRACT:"Metastatic CRPC" OR TITLE:"Castration-resistant metastatic prostate cancer" OR ABSTRACT:"Castration-resistant metastatic prostate cancer" OR TITLE:"Hormone-refractory prostate cancer older term" OR ABSTRACT:"Hormone-refractory prostate cancer older term") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Metastatic castration-resistant prostate cancer, not a curated reading list.
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