A rising PSA profile is indicative of recurrent disease but does not distinguish local from metastatic relapse.

Definition of a PSA recurrence:

1. after radical prostatectomy: two successive increases to a level >0.3ng/ml
2. after radical radiation therapy: relapse may occur following achievement of a nadir, which typically takes 12-24 months to be reached

The ASTRO definition of PSA relapse is three consecutive rises from the nadir, with a minimum value of 0.5ng/ml. This definition, although widely accepted, has been criticized and the Vancouver definition is currently preferred. The Vancouver definition is at least two successive rises to a level of at least 1.5ng/ml.

Patients treated with brachytherapy may experience a ‘bounce’ in the PSA level, typically occurring 1-3 years post-therapy, where PSA levels may rise temporarily to 4 ng/ml or greater. This is thought to be due to a non-infective prostatitis or necrosis. In these patients advice from a radiation oncologist should be sought. Prostate biopsy should not be performed as interpretation is difficult and may be misleading due to continuing tumour cell death ( i.e. most "indeterminate" biopsies performed 2-3 years after prostate brachytherapy are false positives and will revert to negative with longer follow-up). Biopsy results post prostate brachytherapy should thus not be used to guide treatment decisions.

In full detail the ‘Vancouver Rules for PSA relapse following radiation’ are as follows:

1. The true nadir is the lowest post-therapy PSA value. The reference nadir is the lowest reading, which is not followed by a subsequent fall
2. There must be at least two consecutive increases above the reference nadir, measured at least 1 month apart
3. A PSA level of at least 1.5ng/ml is required, at any time after the reference nadir, before PSA relapse can be scored
4. The relapse is timed from mid-way between the reference nadir and the first post-nadir reading
5. Special rules apply where the true nadir is >4: Relapse is scored at the true nadir time. No further rises are needed. If the true nadir occurs over 1 year out from completion of radiation, the relapse is timed at 1 year
6. Patients are also scored as relapsing at the time of any therapeutic intervention (as distinct from neo- or adjuvant hormone therapy). For example, hormones, orchiectomy, salvage therapy etc.