{"entity":{"id":"prostate-high-risk","kind":"cancer","name":"Localised prostate cancer, high and very high risk","aka":["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"],"tldr":"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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer_staging","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer_staging"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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"],"standardOfCare":[{"setting":"High risk","approach":"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.","refs":["imrt-igrt","androgen-deprivation","leuprolide","degarelix","relugolix","brachytherapy","robotic-surgery","hypo-rt-pc"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"Very high risk and node-positive","approach":"Radiotherapy plus androgen deprivation with two years of abiraterone (STAMPEDE); PSMA PET staging before treatment.","refs":["abiraterone","stampede","psma-pet","propsma"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After prostatectomy with adverse pathology","approach":"Adjuvant or early salvage radiotherapy guided by PSA, with hormone therapy for higher-risk features.","refs":["imrt-igrt","androgen-deprivation","psa","biochemical-recurrence"]}],"stateOfArt":["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."],"history":[{"year":1997,"title":"EORTC 22863: adding three years of hormone therapy to radiotherapy improves survival","refs":["androgen-deprivation"]},{"year":2009,"title":"Long-course beats short-course androgen deprivation with radiotherapy in high-risk disease","refs":["androgen-deprivation"]},{"year":2020,"title":"proPSMA: PSMA PET more accurate than conventional staging","refs":["propsma","psma-pet"]},{"year":2022,"title":"STAMPEDE: abiraterone improves survival in high-risk non-metastatic disease","refs":["stampede","abiraterone"]}],"pipeline":["psma-pet","artera-ai-prostate","decipher-prostate","abiraterone"],"openProblems":["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."],"parent":"prostate"},"route":"/cancers/prostate-high-risk/","neighbours":{"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"}],"trial":[{"id":"hypo-rt-pc","kind":"trial","name":"HYPO-RT-PC","route":"/trials/hypo-rt-pc/"},{"id":"propsma","kind":"trial","name":"proPSMA","route":"/trials/propsma/"},{"id":"stampede","kind":"trial","name":"STAMPEDE","route":"/trials/stampede/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"artera-ai-prostate","kind":"drug","name":"ArteraAI Prostate","route":"/drugs/artera-ai-prostate/"},{"id":"decipher-prostate","kind":"drug","name":"Decipher Prostate","route":"/drugs/decipher-prostate/"},{"id":"degarelix","kind":"drug","name":"Degarelix","route":"/drugs/degarelix/"},{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"},{"id":"relugolix","kind":"drug","name":"Relugolix","route":"/drugs/relugolix/"}],"term":[{"id":"biochemical-recurrence","kind":"term","name":"Biochemical recurrence (BCR)","route":"/terms/biochemical-recurrence/"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"}],"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}]}}