Five-year follow-up of prostate specific membrane antigen PET/CT-guided salvage radiotherapy following radical prostatectomy: A single center retrospective analysis.
Authors: Nikitas John , Smith Clayton P , Armstrong Wesley Robert , Murthy Vishnu , Grogan Tristan , Clark Kevyn J , Moore Jonathan , Roberts Makayla , Farolfi Andrea , Reiter Robert Evan , Rettig Matthew , Shen John , Valle Luca , Nickols Nicholas George , Steinberg Michael L. , Czernin Johannes , Kishan Amar Upadhyaya , Calais Jeremie 
Published: February 2025

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Background:
Salvage radiation therapy (sRT) is standard of care for biochemically recurrent prostate cancer following radical prostatectomy (RP). In this setting, prostate specific membrane antigen (PSMA) PET/CT has superior sensitivity and specificity for identifying recurrent disease, especially at low prostate specific antigen (PSA) levels, and can guide target volume delineation for sRT. We set out to identify how PSMA PET/CT guidance impacts long term clinical outcomes following sRT.
Methods:
We retrospectively screened five prospective PSMA PET/CT studies conducted at the University of California, Los Angeles between 2016 and 2021 for patients who had a prior RP, were restaged with a PSMA PET/CT at their first biochemical recurrence (PSA >0.2 ng/mL), subsequently received sRT, and had at least 24 months of follow up from the start of sRT. Progression-free survival (PFS), freedom from distant progression, and overall survival (OS) were calculated from the start of sRT using the Kaplan-Meier method. Cox regression was used to calculate adjusted hazard ratios (aHRs) for PFS, adjusting for androgen deprivation therapy (ADT), age, pre-sRT PSA level, and use of whole pelvis radiotherapy (WPRT).
Results:
113 patients who received sRT between December 2016 and March 2021 met inclusion criteria. Median PSA at PSMA PET/CT was 0.4 ng/mL (IQR, 0.3-1). Median time from RP was 19.9 mo. (IQR, 5.6-51.8 mo). On PSMA PET/CT, 19 patients (17%) were staged TrN0M0, 35 (31%) N1/M1a, 13 (12%) M1b-c, and 46 (41%) T0N0M0 (no visible disease). 76 (67%) received ADT and 70 (62%) received WPRT. Median follow-up was 59.4 mo. (interquartile range [IQR], 47.4-69.5 mo.). 57 (50%) had documented progression. Median PFS was 49.2 mo. (95% confidence interval [CI], 24.1-74.3 mo.). Median freedom from distant progression was 76.4 mo. (95% CI, 62.9-89.9 mo.). Median OS was not reached. The five-year OS rate was 97.1% (95% CI, 94.1-100%). T0N0M0 patients had the most favorable PFS (aHR relative to M1b-c cohort, 0.25) followed by TrN0M0 and N1/M1a patients (aHR relative to M1b-c cohort, 0.39 for both). Pre-radiotherapy PSA was not associated with PFS (aHR, 1.0;
p
=0.98). WPRT was significantly associated with improved PFS in TrN0M0 patients (aHR, 0.12;
p
=0.035) but not in T0N0M0 patients (aHR, 0.87;
p
=0.8). Among T0 N1/M1 patients, prostate bed irradiation was significantly associated with improved PFS (aHR, 0.25;
p
=0.005). Among T0N0M0 and TrN0M0 patients, ADT was not associated with improved PFS (
p
>0.05 for both). Among N1/M1 patients, ADT was significantly associated with improved PFS (aHR, 0.37;
p
=0.02).
Conclusions:
PSMA PET/CT-guided sRT was associated with favorable long-term clinical outcomes. Exploratory analyses suggest a benefit for WPRT following a positive PSMA PET/CT and for ADT for N1 or M1 disease. Further prospective data are needed to confirm these findings.