# Localised prostate cancer, high and very high risk

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

## TL;DR

High-risk prostate cancer has Grade Group 4 or 5 disease, a PSA above 20 or a tumour growing beyond the gland. It is still curable, but needs radiotherapy with two to three years of hormone therapy, or surgery followed by radiotherapy, and adding abiraterone to hormone therapy now lengthens life in the highest-risk men.

## Summary

High-risk localised prostate cancer is defined by the NCCN as any of clinical stage T3a, Grade Group 4 or 5, or PSA above 20 ng/mL; very high risk adds T3b to T4 disease, primary Gleason pattern 5, more than four cores of Grade Group 4 or 5, or two or more high-risk features. It is found by PSA and biopsy and staged with PSMA PET, which proPSMA showed is far more accurate than CT and bone scan. Standard treatment is external beam radiotherapy to the prostate and pelvic nodes with 18 to 36 months of androgen deprivation, often with a brachytherapy boost, or radical prostatectomy with extended node dissection followed by radiotherapy when the pathology warrants it. STAMPEDE showed that adding two years of abiraterone to androgen deprivation and radiotherapy in men with very high risk or node-positive disease cuts metastasis and death, and this is now guideline care for the highest-risk group. Salvage options after failure are covered under biochemical recurrence.

## Fields

- Kind: Cancer
- Last checked: 2026-09-25
- Also known as: High-risk prostate cancer; Very high risk prostate cancer; Locally advanced prostate cancer; Grade Group 4 and 5 prostate cancer; Non-metastatic high-risk prostate cancer; Cambridge Prognostic Group 4; Cambridge Prognostic Group 5; CPG 4; CPG 5; CPG4 prostate cancer; CPG5 prostate cancer
- Tags: subtype-page
- Group: genitourinary
- Burden: About one in five newly diagnosed localised cancers and most of the deaths from disease found before it spreads; ten-year cancer-specific survival is around 85 percent with combined treatment.
- Subtypes: High risk (T3a, or Grade Group 4 or 5, or PSA above 20); Very high risk (T3b to T4, primary pattern 5, more than 4 high-grade cores, or 2 or more high-risk features); Locally advanced adenocarcinoma with seminal vesicle invasion (T3b); Clinically node-positive (N1) non-metastatic disease
- Biomarkers: Gleason Grade Group 4 or 5; PSA above 20 ng/mL; PSMA PET staging; Germline and tumour HRR testing (BRCA2 in particular); Decipher genomic classifier

## 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-high-risk/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-high-risk/#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-high-risk/#what-it-is [4 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-high-risk/#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-high-risk/#treating-it [3 settings, 3 decisions with options]
- Trials and papers (own page): 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-high-risk/evidence/ [38 trials, 16 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-high-risk/#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-high-risk/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-high-risk/#living-with-it [16 questions, 5 red cards, 1 decision aid]
- 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-high-risk/coming/ [6 medicines, 38 trials, 3 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-high-risk/data/ [108 connected records, 2 notes]

## Standard of care

- High risk: External beam radiotherapy to prostate and pelvic nodes with 18 to 36 months of androgen deprivation, with or without brachytherapy boost; or radical prostatectomy with extended lymph node dissection. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Leuprolide (leuprorelin) and GnRH agonists](https://onco.cc/drugs/leuprolide/), [Degarelix](https://onco.cc/drugs/degarelix/), [Relugolix](https://onco.cc/drugs/relugolix/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [HYPO-RT-PC](https://onco.cc/trials/hypo-rt-pc/))
- Very high risk and node-positive: Radiotherapy plus androgen deprivation with two years of abiraterone (STAMPEDE); PSMA PET staging before treatment. ([Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [STAMPEDE](https://onco.cc/trials/stampede/), [PSMA PET](https://onco.cc/technologies/psma-pet/), [proPSMA](https://onco.cc/trials/propsma/))
- After prostatectomy with adverse pathology: Adjuvant or early salvage radiotherapy guided by PSA, with hormone therapy for higher-risk features. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [PSA (prostate-specific antigen)](https://onco.cc/terms/psa/), [Biochemical recurrence (BCR)](https://onco.cc/terms/biochemical-recurrence/))

## State of the art

- PSMA PET has replaced bone scan and CT for staging, reclassifying about a quarter of men.
- Abiraterone with radiotherapy and hormone therapy is the first drug to improve survival in high-risk non-metastatic disease.
- Genomic classifiers and AI pathology are being tested to choose hormone therapy duration.

## Open problems

- How long hormone therapy should last when abiraterone is added.
- Whether PSMA PET-detected nodes should change treatment when the trials were staged conventionally.
- Which men with high-risk disease are better served by surgery than radiotherapy.

## Notes

- What this page is called in the NHS: Cambridge Prognostic Groups 4 and 5. NICE NG131 1.2.15 defines group 4 as any one of Gleason 8 (grade group 4), PSA above 20 or stage T3, and group 5 as two or more of those three, or Gleason 9 to 10 (grade group 5), or stage T4. Active surveillance is not offered in either (1.3.11); radical prostatectomy or radical radiotherapy is offered where the cancer is likely to be controlled in the long term (1.3.12); radiotherapy is combined with androgen deprivation, and continuing it for up to three years is considered in CPG 4 and 5 (1.3.23); brachytherapy alone is not offered (1.3.25).
- Note what puts a man in group 4 on its own: a single T3, which means extraprostatic extension or seminal vesicle invasion. A stage found on MRI rather than by examination will be written cT3(mr) under the ninth edition of TNM, and the TNM committee's reason for introducing the suffix is precisely that imaging finds T3 disease a finger would have called T2.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Prostate_cancer_staging
- Wikipedia: https://en.wikipedia.org/wiki/Prostate_cancer_staging
- 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
- Royal College of Pathologists G084: dataset for histopathology reports for prostatic carcinoma, version 4, October 2024: https://www.rcpath.org/static/8cc88604-2c8d-4df4-a99542df41c102af/G084-dataset-for-histopathology-reports-for-prostatic-carcinoma.pdf

## Connected records

- cancers: [Biochemical recurrence of prostate cancer](https://onco.cc/cancers/prostate-bcr/), [Ductal adenocarcinoma of the prostate](https://onco.cc/cancers/prostate-ductal-adenocarcinoma/), [Localised prostate cancer, intermediate risk](https://onco.cc/cancers/prostate-intermediate-risk/), [Localised prostate cancer, very low and low risk](https://onco.cc/cancers/prostate-low-risk/), [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- terms: [Biochemical recurrence (BCR)](https://onco.cc/terms/biochemical-recurrence/), [Cambridge Prognostic Group (CPG 1 to 5)](https://onco.cc/terms/cambridge-prognostic-group/), [Choosing treatment for localised prostate cancer: what each option costs](https://onco.cc/terms/prostate-treatment-choice-localised/), [Chromoplexy](https://onco.cc/terms/chromoplexy/), [Cribriform growth pattern in prostate cancer](https://onco.cc/terms/cribriform-prostate-cancer/), [Extraprostatic extension and seminal vesicle invasion](https://onco.cc/terms/extraprostatic-extension/), [How many radiotherapy visits: the prostate fractionation trials](https://onco.cc/terms/prostate-radiotherapy-fractionation/), [Intermittent androgen deprivation (IAD)](https://onco.cc/terms/intermittent-androgen-deprivation/), [Intraductal carcinoma of the prostate (IDC-P)](https://onco.cc/terms/intraductal-carcinoma-prostate/), [Metastasis-free survival (MFS)](https://onco.cc/terms/metastasis-free-survival/), [Number needed to screen (and number needed to diagnose)](https://onco.cc/terms/number-needed-to-screen/), [Other-cause mortality](https://onco.cc/terms/other-cause-mortality/), [PI-RADS (Prostate Imaging Reporting and Data System)](https://onco.cc/terms/pi-rads/), [Polygenic risk score (PRS)](https://onco.cc/terms/polygenic-risk-score/), [PSA (prostate-specific antigen)](https://onco.cc/terms/psa/), [STAMPEDE's arms, and what each one answered](https://onco.cc/terms/prostate-stampede-arms/), [Template mapping biopsy (transperineal template prostate mapping)](https://onco.cc/terms/template-mapping-biopsy/), [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/), [Whole-mount pathology](https://onco.cc/terms/whole-mount-pathology/)
- key papers: [Association of Black race with prostate cancer-specific and other-cause mortality](https://onco.cc/key-papers/paper-dess-black-race-prostate-mortality-jama-oncol-2019/), [D'Amico risk groups: biochemical outcome after radical prostatectomy, external beam radiotherapy or brachytherapy](https://onco.cc/key-papers/paper-damico-risk-groups-jama-1998/), [Detection of individual prostate cancer foci via multiparametric magnetic resonance imaging](https://onco.cc/key-papers/paper-johnson-mpmri-individual-foci-eur-urol-2019/), [Diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: a multicenter prospective phase 3 imaging trial](https://onco.cc/key-papers/paper-psma-prerp-hope-jama-oncol-2021/), [EORTC 22863: improved survival with radiotherapy plus goserelin in locally advanced prostate cancer](https://onco.cc/key-papers/paper-bolla-eortc-22863-nejm-1997/), [ERSPC: screening and prostate cancer mortality in a randomised European study](https://onco.cc/key-papers/paper-schroder-erspc-screening-mortality-nejm-2009/), [Integrative genomic profiling of human prostate cancer](https://onco.cc/key-papers/paper-taylor-integrative-genomic-profiling-cancer-cell-2010/), [PROMIS: diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer](https://onco.cc/key-papers/paper-ahmed-promis-multiparametric-mri-lancet-2017/), [proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer](https://onco.cc/key-papers/paper-propsma-hofman-lancet-2020/), [Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate](https://onco.cc/key-papers/paper-stamey-psa-serum-marker-nejm-1987/), [Punctuated evolution of prostate cancer genomes](https://onco.cc/key-papers/paper-baca-punctuated-evolution-chromoplexy-cell-2013/), [Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer](https://onco.cc/key-papers/paper-tomlins-tmprss2-ets-fusion-science-2005/), [SPCG-4: radical prostatectomy or watchful waiting in prostate cancer, 29-year follow-up](https://onco.cc/key-papers/paper-bill-axelson-spcg-4-29-year-nejm-2018/), [STAMPEDE: abiraterone with or without enzalutamide added to androgen deprivation for high-risk non-metastatic prostate cancer](https://onco.cc/key-papers/paper-stampede-abiraterone-high-risk-attard-lancet-2022/), [STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer](https://onco.cc/key-papers/paper-stampede-abiraterone-nejm-2017/), [TCGA: the molecular taxonomy of primary prostate cancer](https://onco.cc/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/)
- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [PSMA PET](https://onco.cc/technologies/psma-pet/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/)
- trials: [A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer](https://onco.cc/trials/nct04557059/), [A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy](https://onco.cc/trials/nct03767244/), [A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation](https://onco.cc/trials/nct06952803/), [A Study to Learn How Well a Combination of Darolutamide and Androgen Deprivation Therapy (ADT) Works as a Treatment Before Surgery for Men Who Have Hi](https://onco.cc/trials/nct07450599/), [An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS](https://onco.cc/trials/nct02531516/), [ARTISTIC meta-analysis](https://onco.cc/trials/artistic-meta-analysis/), [ASCENDE-RT](https://onco.cc/trials/ascende-rt/), [Assessing Efficacy of Neoadjuvant ADT in Localized High-Risk Prostate Cancer Patients Utilizing 18F-Flotufolastat PSMA PET/CT](https://onco.cc/trials/nct07455903/), [Copper Cu 64 PSMA I&T PET Imaging in Men With Newly Diagnosed Prostate Cancer](https://onco.cc/trials/nct06235151/), [DART 01/05 GICOR](https://onco.cc/trials/dart-01-05-gicor/), [Diagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients With Newly-Diagnosed Prostate Cancer](https://onco.cc/trials/nct06122584/), [EORTC 22863](https://onco.cc/trials/eortc-22863/), [EORTC 22911](https://onco.cc/trials/eortc-22911/), [EORTC 22961](https://onco.cc/trials/eortc-22961/), [EORTC 22991](https://onco.cc/trials/eortc-22991/), [ERSPC (European Randomized Study of Screening for Prostate Cancer)](https://onco.cc/trials/erspc/), [FK-PC101 as Adjuvant Therapy for Men With High-Risk Prostate Cancer](https://onco.cc/trials/nct06636682/), [GETUG-AFU 17](https://onco.cc/trials/getug-afu-17/), [HERO](https://onco.cc/trials/hero/), [Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer](https://onco.cc/trials/nct00004054/), [Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer](https://onco.cc/trials/nct00002633/), [HYPO-RT-PC](https://onco.cc/trials/hypo-rt-pc/), [NRG Oncology RTOG 0521](https://onco.cc/trials/rtog-0521/), [PATCH (Prostate Adenocarcinoma Transcutaneous Hormone)](https://onco.cc/trials/patch-transdermal-oestradiol/), [Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Participants With High-risk Prostate Cancer Prior to Radical Prostatectomy](https://onco.cc/trials/nct06056830/), [proPSMA](https://onco.cc/trials/propsma/), [PSMA-PreRP](https://onco.cc/trials/psma-prerp/), [RADICALS-HD](https://onco.cc/trials/radicals-hd/), [RADICALS-RT](https://onco.cc/trials/radicals-rt/), [Randomized Trial of PSMA PET Scan Before Definitive Radiation Therapy for Prostate Cancer](https://onco.cc/trials/nct04457245/), [RAVES (TROG 08.03/ANZUP)](https://onco.cc/trials/raves/), [RTOG 92-02](https://onco.cc/trials/rtog-9202/), [Samarium Sm 153 Lexidronam Pentasodium and 3-Dimensional Conformal Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Rising Prostate-Specific Antigen Levels After Radical Prostatectomy for Prostate Cancer](https://onco.cc/trials/nct00551525/), [SPCG-4 (Scandinavian Prostate Cancer Group Study 4)](https://onco.cc/trials/spcg-4/), [SPCG-7/SFUO-3](https://onco.cc/trials/spcg-7/), [STAMPEDE](https://onco.cc/trials/stampede/), [SWOG 8794](https://onco.cc/trials/swog-8794/), [Two Studies for Patients With High Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a High Gene Risk Score, The PREDICT-RT Trial](https://onco.cc/trials/nct04513717/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [ArteraAI Prostate](https://onco.cc/drugs/artera-ai-prostate/), [Decipher Prostate](https://onco.cc/drugs/decipher-prostate/), [Degarelix](https://onco.cc/drugs/degarelix/), [Leuprolide (leuprorelin) and GnRH agonists](https://onco.cc/drugs/leuprolide/), [Relugolix](https://onco.cc/drugs/relugolix/)
- 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: [Judge a prostate screening programme on metastatic presentation, not on incidence or mortality](https://onco.cc/ideas/idea-prostate-metastatic-presentation-as-the-screening-endpoint/), [Publish a per-lesion miss rate for every prostate MRI service before it is allowed to guide focal treatment](https://onco.cc/ideas/idea-prostate-per-lesion-mri-audit-before-focal-treatment/), [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/)
- people: [Gerhardt Attard](https://onco.cc/people/gerhardt-attard/), [Rakesh Heer](https://onco.cc/people/rakesh-heer/), [Rosalind Eeles](https://onco.cc/people/ros-eeles/)
- companies: [MRC Clinical Trials Unit at UCL](https://onco.cc/companies/mrc-ctu/)

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