Overall Survival with [ ¹⁷⁷ Lu]Lu-PSMA-617 Versus [ ¹⁷⁷ Lu]Lu-PSMA I&T: A Propensity Score–Matched Real-World Analysis

In this study, we compared clinical outcomes and safety profiles of radiopharmaceutical therapy with [¹⁷⁷Lu]Lu-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA I&T in patients with metastatic castration-resistant prostate cancer under real-world conditions. Methods: This single-center retrospective matched-pair analysis included 140 chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer treated with commercially available [¹⁷⁷Lu]Lu-PSMA-617 (7.4 GBq every 6 wk) (n = 70) or in-house produced [¹⁷⁷Lu]Lu-PSMA I&T (6.0 GBq every 8 wk) (n = 70). Propensity score matching was performed on the basis of age, baseline prostate-specific antigen (PSA), and PSA-positive tumor volume and stratified by Gleason score. Overall survival (OS), biochemical response, prognostic factors, and treatment-related toxicity were analyzed. Results: Median OS was comparable between matched cohorts ([¹⁷⁷Lu]Lu-PSMA I&T: 14 mo; range, 9–16 mo; [¹⁷⁷Lu]Lu-PSMA-617: 15 mo; range, 10–21 mo); hazard ratio, 1.18; 95% CI, 0.79–1.78; P = 0.42). Early PSA response was strongly associated with prolonged OS in both cohorts (P < 0.01). Patients treated with [¹⁷⁷Lu]Lu-PSMA-617 demonstrated a greater median PSA decline (−58% vs. −14%, P = 0.02) and higher biochemical response rates (70% vs. 54%). Although quantitative hematologic changes were more pronounced with [¹⁷⁷Lu]Lu-PSMA-617, Common Terminology Criteria for Adverse Events–graded toxicity remained comparable between cohorts. Multivariable analysis revealed that higher baseline levels of lactate dehydrogenase were significantly associated with shorter OS in both cohorts (hazard ratio, 1.03–1.04 per 10 U/L, P < 0.01). Conclusion: Treatment with [¹⁷⁷Lu]Lu-PSMA I&T and [¹⁷⁷Lu]Lu-PSMA-617 resulted in comparable survival outcomes despite different treatment protocols. Greater biochemical responses and subclinical hematologic changes with [¹⁷⁷Lu]Lu-PSMA-617 may reflect higher cumulative radiation exposure, although patient-specific dosimetry data were not available to confirm this hypothesis.