Real-world evaluation of [177Lu]Lu-PSMA-617 RLT in post-taxane mCRPC: feasibility and safety of individualized treatment in a challenging cohort
Misirci M, Rosar F, Khreish F, Burgard C, Blickle A, Bartholomä M, Maus S, Bastian MB, Speicher T, Petto S, Ganz S, Schaefer-Schuler A, Ezziddin S (2026)
Publication Type: Journal article
Publication year: 2026
Journal
DOI: 10.1007/s00259-026-08037-4
Abstract
Purpose: Evaluating efficacy and safety of individualized [177Lu]Lu‑PSMA‑617 radioligand therapy in heavily pretreated post-taxane patients with metastatic castration‑resistant prostate cancer (mCRPC), and to present a comparison with outcomes of non-individualized regimens. Methods: Per‑cycle activities of [177Lu]Lu-PSMA-617 were individualized by normalizing to body surface area and adjusting for renal clearance, hematopoietic function, and tumor burden and progression parameters. 227 post-taxane mCRPC patients with intense PSMA expression on PET/CT were enrolled in the prospective registry (REALITY; NCT04833517) and retrospectively analyzed. PSA progression-free survival (PSA-PFS) and overall survival (OS) according to Kaplan-Meier analysis, Cox proportional‑hazards models with backward elimination for identification of outcome predictors, safety assessment according to CTCAE v5.0. Results: Median administered activity was 7.1 GBq per cycle (range 2.7–11.6 GBq) and cumulative activity 22.3 GBq (range 2.7–77.8 GBq), while patients received a median of 3 cycles within a 6-week interval. After a median follow‑up of 15.9 months (95%CI: 11.2–20.5 months), median PSA‑PFS was 5.1 months (95% CI: 4.0–6.2 months), and median OS 14.5 months (95% CI: 11.4–17.7 months). PSA declined after the first cycle in 63.9% of patients; PSA reduction ≥ 50% occurred in 51.5%. Shortened PSA‑PFS was associated with visceral metastasis (p = 0.001) and ALP ≥ 220 U/L (p = 0.004). Shortened OS was associated with visceral metastasis (p = 0.009), ALP ≥ 220 U/L (p = 0.001), age ≤ 65 years (p = 0.034), hemoglobin < 9 g/dL (p = 0.006), and early biochemical progressive disease after 1–2 courses (p < 0.001). Newly occurring or worsening hematologic or renal impairments ≥ CTCAE °3 were uncommon. Conclusion: In conclusion, the retrospective real-world analysis suggests that individualized, dose-adapted 177Lu based PSMA RLT regimens may provide an opportunity to successfully extend applicability of RLT to more challenging clinical scenarios and a broader patient population without compromising safety and survival outcomes.
Involved external institutions
Germany (DE)How to cite
APA:
Misirci, M., Rosar, F., Khreish, F., Burgard, C., Blickle, A., Bartholomä, M.,... Ezziddin, S. (2026). Real-world evaluation of [177Lu]Lu-PSMA-617 RLT in post-taxane mCRPC: feasibility and safety of individualized treatment in a challenging cohort. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08037-4
MLA:
Misirci, Muammer, et al. "Real-world evaluation of [177Lu]Lu-PSMA-617 RLT in post-taxane mCRPC: feasibility and safety of individualized treatment in a challenging cohort." European Journal of Nuclear Medicine and Molecular Imaging (2026).
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