Prognostic value of PSMA PET against CHAARTED criteria in an ENZAMET sub-cohort.

5091 Background: CHAARTED criteria using CT and bone scan are widely recognized as prognostic in metastatic, hormone-sensitive prostate cancer (mHSPC) and can guide decisions about treatment, including intensification. However, clinicians are increasingly using PSMA PET/CT (PSMA-PET) instead of conventional imaging. Currently, PSMA-PET criteria for identifying poor prognostic mHSPC has limited evidence. The aim of this study is to identify features on PSMA PET/CT that correlate to progression free survival (PFS) and overall survival (OS) in the context of CHAARTED criteria in an ENZAMET sub-cohort. Methods: ENZAMET (ANZUP 1304, NCT02446405) is an international, open-label, randomized, phase 3 trial. Eligible participants had mHSPC evident on CT and/or bone scan. Participants (pts) were randomly assigned (1:1) to receive testosterone suppression plus enzalutamide or a non-steroidal antiandrogen (NSAA). Pts who underwent PSMA-PET prior to study enrolment were identified for this sub-study. Imaging (PSMA-PET, CT, bone scan) were de-identified, and centrally evaluated by three imaging experts blinded to clinical outcomes for number, site, and intensity of metastatic deposits. Additional correlative findings on bone scan and PSMA-PET/CT were determined. A semi-automated quantitative imaging analysis was undertaken to derive PSMA-total tumor volume (PSMA-TTV). The analysis evaluated the association between PSMA-TTV (analysed continuously and as quartiles Q1-3 vs Q4), site (lymph node, bone, viscera) with PFS, OS, and CHAARTED criteria. Kaplan-Meier survival estimates, log-rank tests, and Cox regression after adjusting for treatment arm were used for analysis. Results: 100 pts (51 enzalutamide, 49 control NSAA) had a PSMA-PET/CT prior to enrolment. In this sub-cohort, median age was 69 years, 36 were synchronous, 74 patients were low volume on CHAARTED criteria. On PSMA-PET 19 pts had bone only disease, 37 had lymph node (LN) only, 33 bone and LN and 9 visceral involvement. In 54 pts with bone involvement on PSMA-PET, 53 had concordant findings on bone scan. Median PSMA TTV in the study cohort was 28 mL (61 mL vs 22 mL in CHAARTED high vs low volume) with the highest PSMA TTV quartile (Q4) >71mL. 5-year PFS for PSMA TTV Q4 vs Q1-3 was 36% vs 61% (p=0.011), with HR per doubling of TTV = 1.19 (95%CI: 1.03 – 1.38). In the pts with CHAARTED criteria low volume mHSPC, 5-year PFS for PSMA TTV Q4 vs Q1-3 was 21% vs 57% (p<0.001). 5-year OS for PSMA TTV Q4 vs Q1-3 was 60% vs 74% (p=0.18) with HR per doubling of TTV = 1.10 (95%CI: 0.91 – 1.32). Conclusions: PSMA-TTV is associated with PFS in mHSPC in this ENZAMET sub-cohort with the highest volume quartile (>71mls) showing significantly shorter PFS, including within the CHAARTED criteria low volume cohort. Further validation of PSMA-TTV as a prognostic biomarker with potential to identify patients for intensification is warranted in larger mHSPC cohorts. Clinical trial information: NCT02446405 .