{"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"],"tldr":"Biochemical recurrence 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":"2026-09-17","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"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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":{"term":[{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","route":"/terms/oligometastatic/"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"}],"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":"embark","kind":"trial","name":"EMBARK","route":"/trials/embark/"}],"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/"}],"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}]}}