Biochemical recurrence of prostate cancer
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.
Overview
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.
State of the art
- 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.
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 biochemical recurrence (PSA doubling time under 9 months, non-metastatic hormone-sensitive)
- Transition zone (BPH)
- Ducts (ductal, intraductal, neuroendocrine)
- Seminal vesicle (T3b)
- obturator
- internal iliac
- external iliac
- presacral
Same organ: Prostate cancer, Localised prostate cancer, high and very high risk, Metastatic hormone-sensitive prostate cancer, Non-metastatic castration-resistant prostate cancer, Metastatic castration-resistant prostate cancer, Neuroendocrine and small-cell prostate cancer
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.
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.
Salvage prostatectomy, brachytherapy, cryotherapy or high-intensity focused ultrasound in fit men with biopsy-proven local disease and no metastases on PSMA PET.
Enzalutamide with leuprolide, or enzalutamide alone (EMBARK); PSMA PET before starting; intermittent therapy with treatment suspension when PSA becomes undetectable.
Stereotactic radiotherapy to the visible metastases, usually within trials or with hormone therapy; the survival benefit is unproven.
Subtypes & biomarkers
top- 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
- 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
How often this target appears
- 1997ASTRO consensus defines PSA failure after radiotherapy
- 2005Phoenix definition: nadir plus 2 ng/mL
- 2017RTOG 9601: bicalutamide with salvage radiotherapy improves survival
- 2020PSMA PET approved for recurrence
- 2023EMBARK: enzalutamide delays metastasis in high-risk biochemical recurrence
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 recordBiochemical recurrence of prostate cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2023Trial resultEMBARKEMBARK reported
MFS HR 0.
- 2023Trial resultSPOTLIGHTSPOTLIGHT reported
Overall detection rate 83% by majority read; verified detection rate against a composite standard of truth was 51-54% across readers, meeting the pre-specified threshold, though combined region-level positive predictive value (46-60%) did not (Jani et al.
- 2023MilestoneEMBARKEMBARK: enzalutamide delays metastasis in high-risk biochemical recurrence
A milestone in how this cancer is treated.
- 2021Trial resultCONDORCONDOR reported
Correct localisation rate 84.
- 2020MilestonePSMA PETPSMA PET approved for recurrence
A milestone in how this cancer is treated.
What is in development for Biochemical recurrence of prostate cancer, drawn from the whole corpus: 8 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
Drugs in emerging · 1
Trials under way · 1
- Biodistribution and Dosimetry of Ga-68 P16-093 in Prostate Cancer · phase 1/2 · Five Eleven Pharma, Inc.
Trials reported · 4
Ideas not yet in a trial · 1
Open problems and what is being done
Whether treating PSMA PET-detected metastases early lengthens life or only lowers PSA.
What is being done about thisAdvanced and metastatic diseaseBackground: Oligometastatic disease. Also on Nuclide: Indications.
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.
What is being done about thisRecurrence and residual diseaseAvailable nowNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on Nuclide: Indications.
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
5targets
1drugs
4companies
3terms
2trials
5ideas
1people
1opportunities
1key papers
2This guideline tells doctors and insurers exactly which clinical situations justify a PSMA PET scan for prostate cancer - mainly staging higher-risk disease, investigating a PSA rise after treatment, and checking that a patient's cancer will respond to PSMA radioligand therapy - and which situations do not.
PSMA PET-CT is the preferred staging investigation for high-risk prostate cancer and for biochemical recurrence, though most treatment trials were designed with conventional imaging.
Latest papers
topQuery for this indication: (TITLE:"Biochemical recurrence of prostate cancer" OR ABSTRACT:"Biochemical recurrence of prostate cancer" OR TITLE:"Biochemically recurrent prostate cancer" OR ABSTRACT:"Biochemically recurrent prostate cancer" OR TITLE:"PSA recurrence" OR ABSTRACT:"PSA recurrence" OR TITLE:"Rising PSA after local therapy" OR ABSTRACT:"Rising PSA after local therapy" OR TITLE:"nmHSPC" OR ABSTRACT:"nmHSPC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Biochemical recurrence of prostate cancer, not a curated reading list.
Similar pages
not linked directly; found by shared links- IndicationNeuroendocrine and small-cell prostate cancer
Shares Non-metastatic castration-resistant prostate cancer, Metastatic hormone-sensitive prostate cancer, Metastatic castration-resistant prostate cancer, PSMA PET and the tag subtype-page.
- TermBiochemical recurrence (BCR)
Shares EMBARK, PSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer, Localised prostate cancer, high and very high risk, PSMA PET.
- TrialOSPREY
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- TrialproPSMA
Shares proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer, Localised prostate cancer, high and very high risk, PSMA PET, Prostate cancer.
- TrialSTAMPEDE
Shares Metastatic hormone-sensitive prostate cancer, Localised prostate cancer, high and very high risk, Enzalutamide, Prostate cancer.
- TrialLIGHTHOUSE
Shares SPOTLIGHT, Localised prostate cancer, high and very high risk, PSMA PET.
- CompanyBlue Earth Diagnostics (Bracco)
Shares FALCON, SPOTLIGHT, Prostate cancer.
- TrialPROSPER
Shares Non-metastatic castration-resistant prostate cancer, Enzalutamide, Prostate cancer.