Localised prostate cancer, high and very high risk
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.
Overview
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.
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.
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 (T3a, or Grade Group 4 or 5, or PSA above 20) · Locally advanced adenocarcinoma with seminal vesicle invasion (T3b)
- Transition zone (BPH)
- Ducts (ductal, intraductal, neuroendocrine)
- Seminal vesicle (T3b)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)
- obturator
- internal iliac
- external iliac
- presacral
Same organ: Prostate cancer, Biochemical recurrence of prostate cancer, Metastatic hormone-sensitive prostate cancer, Non-metastatic castration-resistant prostate cancer, Metastatic castration-resistant prostate cancer, Neuroendocrine and small-cell prostate cancer
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.
- 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.
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.
Radiotherapy plus androgen deprivation with two years of abiraterone (STAMPEDE); PSMA PET staging before treatment.
Adjuvant or early salvage radiotherapy guided by PSA, with hormone therapy for higher-risk features.
Subtypes & biomarkers
top- 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
- 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
How often this target appears
- 1997EORTC 22863: adding three years of hormone therapy to radiotherapy improves survival
- 2009Long-course beats short-course androgen deprivation with radiotherapy in high-risk disease
- 2020proPSMA: PSMA PET more accurate than conventional staging
- 2022STAMPEDE: abiraterone improves survival in high-risk non-metastatic disease
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 10 changes by month →- 2026-09-17This recordLocalised prostate cancer, high and very high riskFacts on this page last checked
When this page itself was last checked or edited.
- 2023Trial resultLIGHTHOUSELIGHTHOUSE reported
Specificity for pelvic lymph node metastases met the pre-specified threshold (93-97% across readers) but sensitivity did not (23-30%); the agent additionally identified distant (M1) lesions, later verified true-positive in 10-15% of men (Eur Urol 2023; ASCO GU 2023)
- 2023Trial resultLuTectomyLuTectomy reported
A single dose of neoadjuvant 177Lu-PSMA-617 delivered a median tumour absorbed dose of 35.
- 2022MilestoneSTAMPEDESTAMPEDE: abiraterone improves survival in high-risk non-metastatic disease
A milestone in how this cancer is treated.
- 2021Trial resultOSPREYOSPREY reported
Cohort A: specificity 97.
- 2020Trial resultproPSMAproPSMA reported
Accuracy 92% vs 65%.
What is in development for Localised prostate cancer, high and very high risk, drawn from the whole corpus: 10 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 · 1
Trials under way · 4
- A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer · phase 3 · Janssen Pharmaceutica N.V., Belgium
- Copper Cu 64 PSMA I&T PET Imaging in Men With Newly Diagnosed Prostate Cancer · phase 3 · Curium US LLC
- Diagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients With Newly-Diagnosed Prostate Cancer · phase 3 · ABX advanced biochemical compounds GmbH
- LuTectomy · phase 1/2 · Peter MacCallum Cancer Centre, Australia
Trials reported · 4
- LIGHTHOUSE · phase 3 · 2023 · completed
- OSPREY · phase 2/3 · 2021 · completed
- proPSMA · phase 3 · 2020 · positive
- STAMPEDE · platform trial · 2016 · positive
Ideas not yet in a trial · 1
Open problems and what is being done
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.
Trials
topTrials recruiting now
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Landmark trials
Direct links plus the targets, companies, and technologies of this cancer's products.
fronts
1technologies
3targets
1drugs
3companies
2terms
1trials
8ideas
1key papers
1Latest papers
topQuery for this indication: (TITLE:"Localised prostate cancer, high and very high risk" OR ABSTRACT:"Localised prostate cancer, high and very high risk" OR TITLE:"High-risk prostate cancer" OR ABSTRACT:"High-risk prostate cancer" OR TITLE:"Very high risk prostate cancer" OR ABSTRACT:"Very high risk prostate cancer" OR TITLE:"Locally advanced prostate cancer" OR ABSTRACT:"Locally advanced prostate cancer" OR TITLE:"Grade Group 4 and 5 prostate cancer" OR ABSTRACT:"Grade Group 4 and 5 prostate cancer" OR TITLE:"Non-metastatic high-risk prostate cancer" OR ABSTRACT:"Non-metastatic high-risk prostate cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Localised prostate cancer, high and very high risk, not a curated reading list.
Similar pages
not linked directly; found by shared links- IndicationNon-metastatic castration-resistant prostate cancer
Shares Metastatic hormone-sensitive prostate cancer, Biochemical recurrence of prostate cancer, PSMA PET, Prostate cancer and the tag subtype-page.
- IndicationNeuroendocrine and small-cell prostate cancer
Shares Metastatic hormone-sensitive prostate cancer, PSMA PET, Prostate cancer and the tag subtype-page.
- IndicationMetastatic castration-resistant prostate cancer
Shares Copper-64 SAR-bisPSMA, Abiraterone acetate, Metastatic hormone-sensitive prostate cancer, Biochemical recurrence of prostate cancer and the tag subtype-page.
- IdeaPSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer
Shares Neoadjuvant PSMA radioligand therapy before prostatectomy, Biochemical recurrence (BCR), Biochemical recurrence of prostate cancer, PSMA PET.
- TermRadical prostatectomy
Shares Neoadjuvant PSMA radioligand therapy before prostatectomy, LuTectomy, PSMA PET, Prostate cancer.
- TrialCONDOR
Shares OSPREY, Biochemical recurrence of prostate cancer, PSMA PET.
- CompanyJohnson & Johnson
Shares A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer, Abiraterone acetate, Prostate cancer.
- TermOligometastatic disease
Shares Metastatic hormone-sensitive prostate cancer, Biochemical recurrence of prostate cancer, PSMA PET, Prostate cancer.