The poor outcome of patients with mCRPC whom were deemed ineligible for PSMA theranostics based on molecular imaging characteristics.

e17002 Background: Prostate-specific membrane antigen (PSMA) is overexpressed in the majority of patients with metastatic castrate-resistant prostate cancer (mCRPC) and represents a target for nuclear medicine imaging and therapy. We undertook a prospective trial of 177Lu-PSMA-617 theranostic therapy in men with mCRPC who progressed after standard therapies. The aim of this study is to determine the outcomes of men screened in this study with PSMA PET/CT who were not eligible for 177Lu-PSMA-617 therapy due to inadequate PSMA-expression. Methods: All patients underwent 68Ga-PSMA-11 and 18F-FDG PET/CT as part of trial screening which aimed to identify patients suitable for therapy. Patients were deemed ineligible to proceed with treatment if they had (1) low PSMA-expression defined by SUVmax of tumour involvement less than 1.5 times SUV of liver or (2) sites of FDG-positive PSMA-negative (discordant FDG-avid) disease. Baseline characteristics and subsequent treatments received by these patients following exclusion were recorded. Kaplan-Meier curve was used to determine overall survival (OS) defined from date of screening. Results: 18 patients (age 53-88 y.o) were excluded for theranostic therapy based on low PSMA expression (4), discordant FDG-avid disease (7) or both (7). The median PSA doubling-time was 1.7 months. 17 (72%) had Gleason score ≥8. All patients progressed after docetaxel chemotherapy, 7 (39%) after cabazitaxel and 17 patients (94%) after abiraterone or enzalutamide. Nine patients had subsequent systemic anti-tumour treatment following exclusion from trial. Seventeen of 18 patients died with a median OS of 2.6 months (95% CI 1.7 – 4.4 months), compared to median OS of 13.5 months (95% CI 10.4 – 22.7 months) in 30 eligible patients treated with 177Lu-PSMA-617. Conclusions: Low PSMA-expression or discordant FDG-avid disease in patients with mCRPC who progress after conventional therapies identifies a group with poor prognosis and short survival. The use of FDG PET/CT scan to identify discordant disease may help guide better selection of patients for PSMA-targeting radionuclide therapy.