Association of Early Same-Day Posttherapy Whole-Body SPECT/CT Using Visual RECIP 1.0 with Overall Survival During [ ¹⁷⁷ Lu]Lu-PSMA-617 Therapy for Metastatic Castration-Resistant Prostate Cancer

This article evaluates whether early same-day posttherapy whole-body SPECT/CT assessed using visual RECIP 1.0 is associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) that is positive for prostate-specific membrane antigen (PSMA) and treated with [¹⁷⁷Lu]Lu-PSMA-617, and it assesses concordance among posttherapy SPECT/CT, PSMA PET/CT, and prostate-specific antigen (PSA). <b>Methods:</b> We retrospectively analyzed 158 men with mCRPC who received at least 2 cycles [¹⁷⁷Lu]Lu-PSMA-617 between June 2022 and January 2025. Same-day posttherapy SPECT/CT was performed after each cycle. Early SPECT imaging response was assessed after cycle 2 using visual RECIP 1.0. Baseline tumor burden was classified as low or high volume using CHAARTED criteria on baseline SPECT. Early biochemical response was defined as a PSA decline of at least 50% (PSA50) before cycle 3. OS was the primary endpoint. Kaplan–Meier analysis, log-rank testing, and univariable and multivariable Cox regression were performed. Interim imaging response and concordance were evaluated for SPECT/CT and PSMA PET/CT after cycle 3. <b>Results:</b> Median follow-up was 23.9 mo, and median OS was 14.4 mo. Early SPECT response after cycle 2 was associated with longer OS than occurred with no response (21.5 vs. 11.3 mo, <i>P</i> &lt; 0.001). High-volume baseline disease and absence of PSA50 were associated with shorter OS. The combination of imaging response, baseline tumor burden, and PSA50 improved survival stratification. Patients with high-volume disease and without imaging response were associated with the shortest OS compared with those with low-volume disease and imaging response (10.6 vs. 23.7 mo, <i>P</i> &lt; 0.001). Among patients who underwent interim SPECT/CT and PSMA PET/CT (<i>n</i> = 97), progressive disease on either modality was associated with shorter survival. SPECT, PET, and PSA responses were concordant in 59.8% of patients. Discordant findings reflected differences in imaging timing, sensitivity, and biologic heterogeneity, including PSMA-negative disease. <b>Conclusion:</b> Early same-day posttherapy SPECT/CT assessed using visual RECIP 1.0 was associated with OS in patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617. Integration of early SPECT response, baseline tumor burden, and PSA50 improved survival stratification. Substantial concordance among SPECT, PSMA PET, and PSA response, together with characteristic discordance patterns, supports a complementary role for SPECT/CT in treatment response assessment.