If the PSA remains detectable or starts to rise after a radical prostatectomy, there must be prostate cells producing it. This is almost always the first sign of a persistent or returning cancer. If the PSA becomes detectable the doctor may repeat the test to confirm the level and may monitor the PSA for many months before recommending a treatment. The treatment decision depends on where the likely site(s) of the cancer recurrence is.

One possibility is that the cancer cells remain only in the pelvic region (in the area close to where the prostate was). The tissue removed during surgery, for example, may show that the cancer extends to the cut edge (positive surgical margin), suggesting that some cells may remain in that area. Radiotherapy may be offered immediately after surgery (adjuvant radiotherapy) if the results suggest some cancer remains in the operation site. This may be the case if there is a positive surgical margin, the cancer has spread just outside the prostate (called locally advanced) or the cancer is high grade (Gleason score 8–10).

A bone scan, CT scan or MRI investigation can help to determine if the cancer has spread to other parts of the body. However it is not as useful in men with a PSA only just starting to rise. This is because the amount of cancer is still small and these tests cannot locate small amounts of cancer.

If cancer is identified in the pelvic area and not elsewhere in the body, radiotherapy can be used to treat it. This is called salvage radiotherapy. It has a mild to moderate chance of curing the cancer. Salvage radiotherapy after surgery is most effective if given when the PSA is still low (less than 0.5 ng/mL).

If the PSA continues to rise and the cancer has spread beyond the prostate area, the most common treatment is hormone treatment (removal of male hormone activity), since most prostate cancer cells need male hormone to grow.

There is debate about the best time to start hormone treatment. Many urologists suggest starting before the PSA climbs above 15 ng/mL. This decision depends on the rate at which the PSA is rising and how the man feels about the side effects of this treatment (see Mr PHIP No. 5).