Impact of baseline 18F-flotufolastat PET bone tumor volume for prognosticating severe hematologic toxicity in patients with metastatic castration-resistant prostate Cancer receiving 177Lu-PSMA-targeted radioligand therapy

Abstract

Purpose: This retrospective analysis evaluated the prognostic value of baseline ¹⁸F-flotufolastat-PET bone tumor metrics for severe hematologic toxicity in metastatic castration-resistant prostate cancer (mCRPC) patients treated with [¹⁷⁷Lu]Lu-PSMA-I&T.

Methods: Data from 182 mCRPC patients with baseline ¹⁸F-flotufolastat-PET scans and complete hematologic profiles were analyzed. Bone lesions were semiautomatically delineated, and clinical parameters (e.g., pretreatments, lab results) were assessed. Hematologic adverse events (AEs) were defined per Common Terminology Criteria for Adverse Events version 5.0, with grades 3-4 considered severe. Cox regression was used to identify prognostic factors for AEs.

Results: Baseline bone tumor volume prognosticated leukocytopenia (HR 1.03 per 100 ml, p = 0.036), while the number of bone lesions was prognostic for anemia (HR 1.04 per 10 lesions, p < 0.001) and severe anemia (HR per 10 lesions 1.05, p = 0.009). Higher baseline hemoglobin correlated with reduced leukocytopenia (HR 0.74, p = 0.002), thrombocytopenia (HR 0.80, p = 0.033), and severe anemia (HR 0.52, p < 0.001). Baseline kidney dysfunction was linked to anemia (HR 2.46, p = 0.002) and severe anemia (HR 3.81, p = 0.023). Prior [²²³Ra]Radiumdichloride treatment prognosticated severe thrombocytopenia (HR 6.43, p = 0.021).

Conclusion: Baseline ¹⁸F-flotufolastat-PET metrics and pretherapeutic clinical parameters are key prognostic factors for severe hematologic toxicity in mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-I&T.

Keywords: Bone tumor metrics; Hematologic toxicity; PSMA radioligand therapy; [177Lu]Lu-PSMA-I&T; mCRPC.