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Safety and Efficacy of 177Lu-PSMA Therapy Following 223Radium Treatment: A Retrospective Multinational Real-World
Giulia Giannini1, Mona Kafka1, Hannes Neuwirt2
1Department of Urology, Medical University Innsbruck, Innsbruck, Austria.
Background:
177Lu PSMA therapy is increasingly used for metastatic castration-resistant prostate cancer (mCRPC) treatment. However, data on its efficacy and safety in patients previously treated with 223Ra remain limited.
Methods:
This retrospective, multicenter study evaluated 233 mCRPC patients treated with 177Lu PSMA at 5 European centers. The cohort included 27 patients previously treated with 223Ra and 206 Radium-naive patients. Statistical analyses, including Chi-squared, Mann-Whitney U tests, and multivariate logistic regression, were used to assess response and mortality. Predictors of response and mortality were identified using multivariate models.
Results:
Patients who experienced a longer interval between castration resistance and the initiation of 177Lu PSMA therapy demonstrated better responses (median 17 months in responders vs. 8.5 months in progressors, P = .001). Platelet counts were significantly lower in the progressive group compared to the responsive group (P = .01). Multivariate regression confirmed lower platelet levels as a predictor of poor response (P = .029). The overall response rate to 177Lu PSMA was 54%, similar between the 223Ra-pretreated and Radium-naive groups. However, mortality was significantly higher in the 223Ra-pretreated group (86%) compared to the Radium-naive group (51%, P = .003). ECOG performance status (P = .004) and ALP levels (P = .030) were significant predictors of mortality, while CRP showed a trend towards significance (P = .064). Tolerability of 177Lu PSMA was comparable to the safety profile reported in the literature, with 44% of 223Ra-pretreated patients experiencing AEs and 22% experiencing severe AEs (Grade ≥ 3).
Conclusions:
177Lu PSMA therapy is effective and well-tolerated in mCRPC patients pretreated with 223Ra. However, higher mortality was observed in the 223Ra-pretreated group. ECOG PS, ALP, and platelet counts were significant predictors of response and mortality, and a longer interval between therapies was associated with better outcomes. These findings underscore the importance of treatment sequencing and monitoring prognostic markers.
