Abstract

5078 Background: The high sensitivity of PSMA PET/CT in pts with PC has created a new advanced disease space (PSMA+/CT-) with stage migration. Treatment outcomes and optimal management remain largely unstudied for these pts. Methods: Pts with metastatic castration sensitive PC identified during standard of care PMSA PET/CT imaging (Ga68 gozetotide/PSMA-11) were reviewed retrospectively at UTSW and stratified by whether a CT lesion correlates to a PSMA avid lesion (SUVmax >2.5): PSMA+/CT- vs PSMA+/CT+ groups. The primary objective was PSA Progression Free Survival (PFS) and time to castration resistance (TTCR) between cohorts. The secondary objective was TTCR in pts with PSMA+/CT- disease based on exposure to androgen deprivation therapy (ADT) alone or with AR-targeted therapy (ARTT intensification). Cohorts were compared using a two-sample t-test or a chi-square test; survival analysis was conducted using Kaplan-Meier and Cox proportional hazards regression. Results: Overall,135 pts were included; of whom 122 received ADT (PSMA+/CT- [n=73] vs PSMA+/CT+ [n=49]) and 13 PMSA+/CT- pts received localized treatment only. PSMA+/CT- and PSMA+/CT+ pts had comparable median age at diagnosis and similar racial distribution. The median follow-up was 19 months. In pts who received ADT, the PSMA+/CT- group had a lower median PSA (1.3 vs 14 ng/ml, P=0.0002), a lower rate of de-novo metastatic disease (30% vs 55%, p=0.0082) and ADT+ ARTT use (59% vs 88%, p=0.0006) compared to the PMSA+/CT+ group. Median therapy duration was similar. In pts receiving ADT, the median PSA PFS in the PSMA+/CT- group was not reached (NR) versus 37 months in the PSMA+/CT+ group. After adjusting for known prognostic factors, PSMA+/CT- lesions were significantly associated with a better PSA PFS and TTCR (Table). In pts with PMSA+/CT- receiving ADT alone (n=30) vs ADT+ARTT (n=43), only 1 patient progressed to castration resistance. After adjusting for prognostic factors, pts with PSMA+CT- disease who received ADT had a better PSA PFS [HR 0.1 (0.02-0.45)] compared to those who received localized therapy only (n=13). Conclusions: Pts with PSMA+CT- PC vs pts with PSMA+/CT+ PC have better prognosis and outcomes, with low rates of PSA progression and castration resistance. Localized therapy alone is likely insufficient for these pts, and ARTT intensification to improve longer term outcomes needs prospective studies through ongoing trials. [Table: see text]