Biochemical Recurrence (Rising PSA) After Prostate Care

This page is for men whose PSA has started to rise after prostate cancer treatment, and their families. It explains what biochemical recurrence means, how it is defined, and what options may follow.

After treatment for prostate cancer, PSA (prostate-specific antigen, a protein made by prostate cells) is checked at set intervals. When it starts to rise, that is called biochemical recurrence. It means a blood test has changed. It does not mean cancer has been found anywhere on a scan. It is not the same thing as metastatic disease.

NCI says a rising PSA after treatment may be the first sign of recurrence. It says this change usually shows up months or years before the cancer causes symptoms. NCI also says a single high PSA does not always mean the cancer has come back. So doctors may look at the trend over time.

NCI says many men with a rising PSA stay free of symptoms for long periods. In one study NCI describes, 103 of 315 men (34%) with a PSA of 0.2 ng/mL or higher after surgery later had clinical signs of recurrence. In that group, the median time to metastasis was 8 years. Nothing on this page can tell you what your own PSA means. ACS says how fast the PSA is rising and the original Gleason score can help predict how soon cancer might show up elsewhere. The Gleason score describes how abnormal the cancer cells looked.

After radical prostatectomy, the gland has been removed. NCI describes a PSA of 0.2 ng/mL or higher as evidence of biochemical recurrence. Ask which number your team uses for you.

After radiation therapy, the prostate is still in place. In a trial summary, NCI describes recurrence as a PSA more than 2 ng/mL above the lowest value reached. That lowest value is called the nadir. NCI cites the Phoenix consensus, from ASTRO and RTOG, for defining PSA failure after radiation. NCI also notes that past studies used different definitions. So ask your team which one they use.

Because the thresholds differ, PSA numbers after surgery and after radiation are not directly comparable. Neither are the timelines.

After radiation, PSA sometimes rises for a while and then falls again on its own. This is called a bounce. It has been studied most after brachytherapy, a type of internal radiation. In one study of men treated with brachytherapy, 26% had a bounce by two years. It was more common in younger men. A bounce goes away without treatment. But one number cannot show whether a rise is a bounce or a recurrence. Ask whether a repeat test is the next step, before anything else happens.

Not all rising PSAs behave alike. One useful clue is how fast the PSA is rising. That is PSA doubling time, worked out from several values over time.

NCI reports early data that a short doubling time (less than 3 months in that study) was linked to a higher risk of death after surgery or radiation. In the EMBARK trial, NCI says high-risk recurrence was defined as a doubling time of 9 months or less, with other findings. ACS says that if the PSA is rising very quickly, some doctors may suggest treatment before cancer shows on tests or causes symptoms. ACS also says observation may be more appealing if you are older and the PSA is rising slowly.

This is why your team may ask you to repeat PSA at intervals rather than acting on the first abnormal value. It is not delay. The trend carries more information than any single point.

PSMA PET is a newer kind of scan. It uses a radioactive tracer that binds prostate-specific membrane antigen (PSMA). PSMA is found at high levels in prostate cancer. NCI says PSMA PET tracers have been tested for imaging suspected recurrence when the PSA is elevated after treatment.

The FDA approved piflufolastat F 18 (Pylarify) on May 27, 2021. NCI says the FDA approved PSMA PET agents in 2020 and 2021 for people with a rising PSA after treatment.

A scan may show a spot. It may show lymph nodes. It may show nothing at all. What it shows can change the plan. Ask whether a scan makes sense for you now.

What comes next depends on your earlier treatment and on what tests show. "Salvage" treatment means treatment given after the first treatment did not fully work. ACS lists these options:

• Radiation to the area where the prostate was, after surgery
• Surgery or ablative therapy after radiation, which carry a higher risk of side effects
• Hormone therapy
• Observation, if a rising PSA is the only sign
• A clinical trial

ACS says observation may suit some men because prostate cancer often grows slowly. NCI says the evidence is limited on whether treating a rising PSA in men without symptoms helps them live longer. So this is a real choice to talk through with your team.

There is no single correct answer. The trade-off between controlling disease and the side effects of further treatment is a legitimate part of the decision.

• What definition of recurrence are you using, and what is my doubling time?
• Is a PSMA PET a good next step for me now?
• What is the goal of any proposed treatment: cure, delay, or symptom prevention?
• What happens if I do nothing for three months?

• NCI: Prostate-specific antigen (PSA) test fact sheet
• NCI: Prostate Cancer Treatment (PDQ), Health Professional Version
• NCI: Prostate Cancer Treatment (PDQ), Patient Version
• ACS: Treating Prostate Cancer That Doesn't Go Away or Comes Back After Treatment
• FDA: FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer
• PubMed: Prediction of PSA bounce after permanent prostate brachytherapy