Background: In the phase 3 VISION study, gallium (⁶⁸Ga) gozetotide (⁶⁸Ga-PSMA-11) PET/CT imaging was used to determine eligibility for lutetium (¹⁷⁷Lu) vipivotide tetraxetan (¹⁷⁷Lu-PSMA-617). Given that ¹⁷⁷Lu-PSMA-617 targets PSMA, we assessed the association between quantitative PSMA imaging parameters and treatment outcomes. Methods: In VISION, adults with mCRPC with ≥ 1 PSMA-positive (+) and no PSMA-negative lesions meeting the exclusion criteria were enrolled. In this sub-study, the association between imaging data from pre-enrollment ⁶⁸Ga-PSMA-11 PET/CT scans of pts in the ¹⁷⁷Lu-PSMA-617 group and clinical outcomes was assessed. Imaging data meeting quality requirements were analyzed for 548/551 pts. PSMA expression was quantified by 5 PET parameters: PSMA+ lesions by region, mean standardized uptake value (SUV_mean), maximum SUV (SUV_max), PSMA+ tumor volume, and tumor load (PSMA+ tumor volume × SUV_mean). Parameters were extracted from the whole body and 4 regions. Association between PET parameters and radiographic progression-free survival (rPFS; primary objective), overall survival (OS), objective response rate (ORR), and prostate–specific antigen 50 (PSA50) response was assessed. Results: Most pts (92.7%) had PSMA uptake in bone. In both the whole-body and regional analyses, statistically significant associations of PSMA PET parameters to clinical outcomes were observed (whole-body data shown in Table). Higher whole-body SUV_mean was associated with improved clinical outcomes; pts in the highest quartile (SUV_mean: rPFS, ≥ 10.2; OS, ≥ 9.9) had a median rPFS and OS of 14.1 and 21.4 months, vs 5.8 and 14.5 months for those in the lowest quartile (< 6.0; < 5.7), respectively. Absence of PSMA+ lesions in bone, liver, and lymph node, and lower PSMA+ tumor load, were indicators of good prognosis. Conclusions: Higher SUV_mean is strongly associated with improved outcomes with ¹⁷⁷Lu-PSMA-617; clinical efficacy for different SUV levels vs the SoC arm is being assessed. Data support use of ⁶⁸Ga-PSMA-11 PET/CT scan to identify pts who will benefit from PSMA-targeted radioligand therapy.

^aPer unit increase for continuous variables. ^bHazard ratio [95% CI], p value; ^cOdds ratio [95% CI], p value. NS, not significant.