{"entity":{"id":"prostate-bcr","kind":"cancer","name":"Biochemical recurrence of prostate cancer","aka":["Biochemically recurrent prostate cancer","PSA recurrence","Rising PSA after local therapy","nmHSPC","Hormone-relapsed prostate cancer, PSA-only","Rising PSA after treatment"],"tldr":"Biochemical recurrence of prostate cancer is a rising PSA after surgery or radiotherapy with nothing yet visible on scans. Salvage radiotherapy can still cure it after surgery, and for a fast-doubling PSA the EMBARK trial showed that enzalutamide with or without hormone therapy delays spread.","summary":"Biochemical recurrence is defined as a PSA of 0.2 ng/mL or more, confirmed, after radical prostatectomy, or a rise of 2 ng/mL above the nadir after radiotherapy (the Phoenix definition). It is found by routine PSA follow-up; PSMA PET now locates the recurrence in most men once PSA passes about 0.5 ng/mL, and often shows disease that conventional imaging misses. After prostatectomy, early salvage radiotherapy to the prostate bed, started before PSA reaches 0.5, cures many men, with short-term hormone therapy added for higher-risk features. After radiotherapy, local salvage by surgery, brachytherapy, cryotherapy or high-intensity focused ultrasound is possible for confirmed local recurrence. Men with a PSA doubling time under nine months are at high risk of metastasis: EMBARK randomised 1,068 such men and showed enzalutamide with leuprolide, or enzalutamide alone, cut metastasis or death by about half compared with leuprolide alone, and the FDA approved enzalutamide for this setting in 2023. Slowly rising PSA can be watched, and PSMA PET-directed stereotactic radiotherapy to a few metastases is under study.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Biochemical_recurrence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biochemical_recurrence"},{"label":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":["subtype-page"],"related":["prostate-high-risk","prostate-intermediate-risk","prostate-nmcrpc","prostate-mhspc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa-kinetics","cambridge-prognostic-group","extraprostatic-extension","tnm-prostate-cancer","psa-density","metastasis-free-survival","intermittent-androgen-deprivation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-embark-nejm-2023","paper-radicals-rt-lancet-2020","paper-propsma-hofman-lancet-2020"],"journals":[],"dependsOn":[],"notes":["The findings on the prostatectomy report that raise the chance of arriving here are extraprostatic extension (pT3a), seminal vesicle invasion (pT3b) and a positive surgical margin, which are three different things: the first two say how far the cancer grew, the third says whether the surgeon's cut passed through cancer, and a man can have one without the others."],"group":"genitourinary","burden":"A rising PSA follows a quarter to a third of prostatectomies and radiotherapy courses; only a minority of these men develop metastases on scans within ten years, and the PSA doubling time tells the two apart.","subtypes":["Biochemical recurrence after prostatectomy (PSA 0.2 or more)","Biochemical recurrence after radiotherapy (nadir plus 2)","High-risk biochemical recurrence (PSA doubling time under 9 months, non-metastatic hormone-sensitive)","PSMA PET-detected oligorecurrence"],"biomarkers":["PSA and PSA doubling time","PSMA PET (positive in most men above 0.5 ng/mL)","Decipher on the prostatectomy specimen","Interval from local therapy to recurrence"],"standardOfCare":[{"setting":"After prostatectomy","approach":"Early salvage radiotherapy to the prostate bed, with or without pelvic nodes and four to six months of androgen deprivation for adverse features; observation for slow doubling times.","refs":["imrt-igrt","androgen-deprivation","psa","decipher-prostate"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"After radiotherapy, local recurrence","approach":"Salvage prostatectomy, brachytherapy, cryotherapy or high-intensity focused ultrasound in fit men with biopsy-proven local disease and no metastases on PSMA PET.","refs":["robotic-surgery","brachytherapy","hifu-histotripsy","psma-pet"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"High-risk biochemical recurrence (doubling time under 9 months)","approach":"Enzalutamide with leuprolide, or enzalutamide alone (EMBARK); PSMA PET before starting; intermittent therapy with treatment suspension when PSA becomes undetectable.","refs":["enzalutamide","leuprolide","embark","psma-pet"],"guideline":{"version":"NCCN Guidelines: Prostate Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459"}},{"setting":"PSMA PET-detected oligorecurrence","approach":"Stereotactic radiotherapy to the visible metastases, usually within trials or with hormone therapy; the survival benefit is unproven.","refs":["sbrt","oligometastatic","idea-psma-pet-guided-mdt"]}],"stateOfArt":["PSMA PET has turned biochemical recurrence from an invisible number into a map, though it also finds disease the trials never saw.","EMBARK is the first trial to show that treating a fast-rising PSA with an androgen receptor inhibitor delays metastasis.","Intermittent therapy with a treatment holiday is built into the approved EMBARK regimen."],"history":[{"year":1997,"title":"ASTRO consensus defines PSA failure after radiotherapy","refs":["psa"]},{"year":2005,"title":"Phoenix definition: nadir plus 2 ng/mL","refs":["psa"]},{"year":2017,"title":"RTOG 9601: bicalutamide with salvage radiotherapy improves survival","refs":["bicalutamide"]},{"year":2020,"title":"PSMA PET approved for recurrence","refs":["psma-pet"]},{"year":2023,"title":"EMBARK: enzalutamide delays metastasis in high-risk biochemical recurrence","refs":["embark","enzalutamide"]}],"pipeline":["psma-pet","enzalutamide","sbrt","idea-psma-pet-guided-mdt"],"openProblems":["Whether treating PSMA PET-detected metastases early lengthens life or only lowers PSA.","How to spare men with slow doubling times from years of hormone therapy.","The trials that defined recurrence used conventional imaging; PSMA PET restages many of these men as metastatic."],"parent":"prostate"},"route":"/cancers/prostate-bcr/","neighbours":{"cancer":[{"id":"prostate-high-risk","kind":"cancer","name":"Localised prostate cancer, high and very high risk","route":"/cancers/prostate-high-risk/"},{"id":"prostate-intermediate-risk","kind":"cancer","name":"Localised prostate cancer, intermediate risk","route":"/cancers/prostate-intermediate-risk/"},{"id":"prostate-low-risk","kind":"cancer","name":"Localised prostate cancer, very low and low risk","route":"/cancers/prostate-low-risk/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate-nmcrpc","kind":"cancer","name":"Non-metastatic castration-resistant prostate cancer","route":"/cancers/prostate-nmcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"term":[{"id":"cambridge-prognostic-group","kind":"term","name":"Cambridge Prognostic Group (CPG 1 to 5)","route":"/terms/cambridge-prognostic-group/"},{"id":"extraprostatic-extension","kind":"term","name":"Extraprostatic extension and seminal vesicle invasion","route":"/terms/extraprostatic-extension/"},{"id":"intermittent-androgen-deprivation","kind":"term","name":"Intermittent androgen deprivation (IAD)","route":"/terms/intermittent-androgen-deprivation/"},{"id":"metastasis-free-survival","kind":"term","name":"Metastasis-free survival (MFS)","route":"/terms/metastasis-free-survival/"},{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","route":"/terms/oligometastatic/"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"},{"id":"psa-density","kind":"term","name":"PSA density","route":"/terms/psa-density/"},{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","route":"/terms/psa-kinetics/"},{"id":"tnm-prostate-cancer","kind":"term","name":"TNM staging for prostate cancer, and what changed in the 9th edition","route":"/terms/tnm-prostate-cancer/"}],"paper":[{"id":"paper-embark-nejm-2023","kind":"paper","name":"EMBARK: enzalutamide with or without leuprolide in high-risk biochemically recurrent prostate cancer","route":"/key-papers/paper-embark-nejm-2023/"},{"id":"paper-propsma-hofman-lancet-2020","kind":"paper","name":"proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer","route":"/key-papers/paper-propsma-hofman-lancet-2020/"},{"id":"paper-radicals-rt-lancet-2020","kind":"paper","name":"RADICALS-RT: timing of radiotherapy after radical prostatectomy","route":"/key-papers/paper-radicals-rt-lancet-2020/"}],"drug":[{"id":"bicalutamide","kind":"drug","name":"Bicalutamide","route":"/drugs/bicalutamide/"},{"id":"decipher-prostate","kind":"drug","name":"Decipher Prostate","route":"/drugs/decipher-prostate/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"}],"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":"hifu-histotripsy","kind":"technology","name":"Focused ultrasound & histotripsy","route":"/technologies/hifu-histotripsy/"},{"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/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}],"trial":[{"id":"nct06970847","kind":"trial","name":"64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 3 Study of Participants With Biochemical Recurrence of Prostate Cancer","route":"/trials/nct06970847/"},{"id":"nct05794906","kind":"trial","name":"A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) and Placebo Given With ADT in Men With Hormone Sensitive Prostate Cancer","route":"/trials/nct05794906/"},{"id":"artistic-meta-analysis","kind":"trial","name":"ARTISTIC meta-analysis","route":"/trials/artistic-meta-analysis/"},{"id":"nct03444844","kind":"trial","name":"Biodistribution and Dosimetry of Ga-68 P16-093 in Prostate Cancer","route":"/trials/nct03444844/"},{"id":"nct01054079","kind":"trial","name":"Cinacalcet Hydrochloride in Treating Men With Recurrent Prostate Cancer","route":"/trials/nct01054079/"},{"id":"embark","kind":"trial","name":"EMBARK","route":"/trials/embark/"},{"id":"eortc-22911","kind":"trial","name":"EORTC 22911","route":"/trials/eortc-22911/"},{"id":"getug-afu-16","kind":"trial","name":"GETUG-AFU 16","route":"/trials/getug-afu-16/"},{"id":"getug-afu-17","kind":"trial","name":"GETUG-AFU 17","route":"/trials/getug-afu-17/"},{"id":"nct00003653","kind":"trial","name":"Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer","route":"/trials/nct00003653/"},{"id":"oriole","kind":"trial","name":"ORIOLE","route":"/trials/oriole/"},{"id":"nct06617481","kind":"trial","name":"PET Scan Study to Detect Prostate Cancer in Patients with Early PSA Recurrence","route":"/trials/nct06617481/"},{"id":"nct00567580","kind":"trial","name":"Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer","route":"/trials/nct00567580/"},{"id":"radicals-hd","kind":"trial","name":"RADICALS-HD","route":"/trials/radicals-hd/"},{"id":"radicals-rt","kind":"trial","name":"RADICALS-RT","route":"/trials/radicals-rt/"},{"id":"raves","kind":"trial","name":"RAVES (TROG 08.03/ANZUP)","route":"/trials/raves/"},{"id":"stomp-oligorecurrence","kind":"trial","name":"STOMP","route":"/trials/stomp-oligorecurrence/"},{"id":"swog-8794","kind":"trial","name":"SWOG 8794","route":"/trials/swog-8794/"},{"id":"nct04423211","kind":"trial","name":"Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging","route":"/trials/nct04423211/"}],"idea":[{"id":"idea-psma-pet-guided-mdt","kind":"idea","name":"PSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer","route":"/ideas/idea-psma-pet-guided-mdt/"}],"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/prostate-roadmap/"}],"person":[{"id":"chris-parker","kind":"person","name":"Chris C. Parker","route":"/people/chris-parker/"},{"id":"stephen-freedland","kind":"person","name":"Stephen J. Freedland","route":"/people/stephen-freedland/"}],"biomarker":[{"id":"psma-pet-expression","kind":"biomarker","name":"PSMA expression by PET (PSMA-positive)","route":"/biomarkers/psma-pet-expression/"}]}}