PSMA PET findings in an "EMBARK-like" cohort of patients with high-risk non-metastatic hormone-sensitive prostate cancer: A single center post-hoc retrospective analysis

5091 Background: The EMBARK trial is a phase 3, randomized, study evaluating use of enzalutamide with or without concomitant leuprolide in non-metastatic castrate sensitive prostate cancer patients. Eligibility status for the trial relied upon conventional imaging which under detects metastatic disease in comparison to PSMA-PET imaging. The aim of this post-hoc retrospective analysis was to describe the PSMA-PET findings in a patient population representative of the EMBARK trial. Methods: This was a post-hoc, retrospective analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP, RT or SRT. Patients were included if they met eligibility for enrollment in the EMBARK trial at the time of their PSMA scan defined as the following: Rising PSA at a level above 1.0ng/mL (post RP and SRT) or 2.0ng/mL > nadir (post-RT), PSA doubling time ≤ 9 months, Serum testosterone ≥ 150 ng/dL. Exclusion criteria constituted: distant metastatic disease as assessed by radiographic imaging, prior hormonal therapy or systemic therapy for prostate cancer. PSMA PET findings (PROMISE miTNM stage, number of lesions) were collected from the clinical imaging reports. Descriptive statistics were used (median, range). Results: From 2002 patients screened, 146 patients were included in the analysis. Median time from primary therapy to PSMA PET was 39 (2.1-261) months. Median pre-scan PSA levels and PSA doubling time in patients who underwent RP (n=85), dRT (n=22), post-RP SRT (n=39) and overall (n=146) were 2.4 ng/mL (1-72.1), 8.3 ng/mL (2.37-202), 2.58 ng/ml (1.1-32.3), 2.7 ng/mL (1-202), and 3.5 months (1-9), 3.3 months (1-9), 4.4 months (1-9), 3.7 (1-9) months, respectively. PSMA-PET was positive in 80%, 41%, 85%, 83% of the RP, dRT, RP + SRT and overall populations, respectively. Poly-metastatic disease (≥5 lesions) was found in 19%, 32%, 21% and 21% of cases, respectively. PSMA-PET detected disease only localized to the prostate fossa (miT+N0M0) in 7%, 32%, 0% and 9% respectively. PSMA-PET detected pelvic nodal disease (miTxN1M0) in 40% 18% 28% and 34% respectively. PSMA PET detected any distant metastatic disease (miTxNxM1) in 33%, 41% 56% and 40% respectively. PSMA-PET detected metastatic nodal only disease (N1 and/or M1a) in 58% 32% 74% and 39% and osseous disease (M1b) in 19% 23% 31% and 23% cases respectively. Conclusions: In this “EMBARK-like” cohort of patients with high-risk nmCS PCa and PSA DT < 9 months, PSMA PET was positive in 83% of patients, detected M1 disease in 40% of patients and over one-fifth of cases presented with 5 or more lesions. PSMA-PET provides novel additional risk stratification for patients with high-risk nmCS PCa without distant metastasis based on conventional imaging. Further studies are needed to assess its independent prognostic value and use for treatment guidance. Clinical trial information: NCT03582774 .