Impact of baseline PSMA PET in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) starting first-line (1L) androgen receptor signaling inhibitor (ARSI) therapy.

46 Background: The prognostic significance of PSMA positron-emission tomography (PET) uptake on prostate cancer (PC) outcomes is not well established. Higher uptake predicts recurrence in men with localized PC, but may be associated with improved survival in pts with mCRPC receiving chemotherapy or radioligand therapy. We sought to evaluate the predictive and prognostic value of baseline PSMA PET uptake in mCRPC pts starting 1L ARSI therapy. Methods: A retrospective analysis of consecutive mCRPC pts who underwent PSMA PET imaging at our institution from 2016 to 2023 was undertaken. Pts were included if a PSMA PET scan performed in the setting of mCRPC showed ≥1 lesion with SUV max ≥3 and 1L ARSI was initiated as the immediate next-line of therapy after scan. PSMA PETs were analyzed and manually segmented by a trained radiologist using MIM Software and SUV threshold of 3; physiologic uptake was removed. SUV max , SUV mean , tumor volume (TV) and total lesion PSMA (TL-PSMA = SUV mean x TV) were obtained for each patient. PSA response on 1L ARSI therapy, PSA progression-free survival (PSA-PFS), time to next treatment (TNT), and overall survival (OS) were retrospectively assessed from start of ARSI. Baseline PSMA PET characteristics were compared across pts with vs without PSA response to 1L ARSI. Time-to-event statistics were performed using the Kaplan-Meier method and Cox proportional hazards model. Statistical significance was declared for p < 0.05. Results: Forty-nine mCRPC pts with PSMA PET imaging performed prior to 1L ARSI (abiraterone in 27, 2 nd generation AR antagonist in 22) were identified. Median SUV max , SUV mean , TV and TL-PSMA were 30.5, 7.2, 22.5 mL and 221.1, respectively. Pts who achieved a greater than ≥90% decline in PSA on ARSI therapy (n=24) had significantly lower SUV max (median 17.7 vs 40.2, p=0.029) and SUV mean (median 6.3 vs 9.9, p=0.017) at baseline. Baseline SUV mean , SUV max , and TV did not predict PSA-PFS, TTNT or OS; however, baseline log10-transformed TL-PSMA was associated with inferior PSA-PFS (HR 1.76, 95% CI 1.07-2.91 p=0.026) on univariate analysis. On Kaplan-Meier analysis, pts in the highest quartile of TL-PSMA had a significantly shorter median OS compared to others (25.3 vs 67.3 months, log-rank p=0.039). Conclusions: In this cohort of mCRPC pts treated with 1L ARSI, those achieving a PSA90 response had significantly lower SUV max and SUV mean on baseline PSMA PET. However, PSMA uptake did not predict longer-term outcomes such as PSA-PFS, TTNT and OS. Pts with higher PSMA-TL had a higher risk of PSA progression and shorter OS. These hypothesis-generating results suggest that although lower PSMA PET uptake may predict initial response to ARSI, tumor burden (PSMA-TL) is a stronger predictor of long-term outcomes. Prospective validation is needed.