To characterize the kinetics of prostate-specific antigen (PSA) after radiotherapy (RT) and neoadjuvant hormonal therapy (NHT) for localized prostate cancer.

The PSA kinetics of 75 consecutive patients who had undergone RT and NHT (median time 4 months) were followed up for a minimum of 24 months after treatment. RT included a permanent iodine-125 implant (n = 29), a temporary iridium-192 implant as a boost to external beam RT (n = 21), and sole external beam RT (n = 25). A median number of 11 PSA levels per patient were analyzed.

After a first nadir (median level 0.1 ng/mL 3 months after RT), rising PSA levels were found in 83% of patients and progressively rising PSA levels until the end of follow-up or salvage hormonal therapy for 21% of patients. The PSA levels dropped again after one (23%), two (21%), or more (17%) consecutive increases up to a median level of 0.6 ng/mL (median time 16 months after RT), so that a nadir of 0.1 ng/mL was reached for a second time (median time 35 months after RT). A first nadir of less than 0.1 ng/mL, a PSA increase of less than 1 ng/mL, and a longer PSA doubling time (median time 10 months) were strongly predictive for long-term biochemical control.

Temporarily rising PSA levels can be expected for most patients after primary RT and NHT following a first nadir. The increasing effects of testosterone owing to NHT withdrawal have a stronger effect than RT in the first months after treatment.