⁶⁸Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% (n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% (n = 71/99). Forty-five percent (n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% (n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% (n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n = 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy.

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