Is Eligibility Enough? Pretreatment Prediction of Failure to Reach a Second Cycle of [¹⁷⁷Lu]Lu-PSMA Radioligand Therapy.

Abstract

Background/Objectives: Current guidelines define no absolute contraindication to prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), yet some patients receive only a single cycle. We aimed to characterize this single-cycle attrition (SCA) and derive an exploratory pretreatment risk score predicting it. Methods: Seventy consecutive patients with metastatic castration-resistant prostate cancer treated with [¹⁷⁷Lu]Lu-PSMA RLT at one center (2022-2025) were reviewed; 58 were assessable. SCA was defined as permanent non-initiation of a second cycle. The analyses employed false-discovery-rate-adjusted nonparametric comparisons, receiver operating characteristic (ROC), Kaplan-Meier and univariable Cox methods, with optimism-corrected bootstrap internal validation. Results: SCA occurred in 12 of 58 patients (20.7%), owing to death or rapid clinical deterioration (n = 8) or grade 3-4 hematotoxicity (n = 4); all 12 died (median overall survival 3 months). Higher C-reactive protein (CRP), lower lymphocytes and hemoglobin, and higher alkaline phosphatase (ALP) and prostate-specific antigen (PSA) separated the groups (all q Conclusions: One in five patients who initiated RLT did not proceed beyond the first cycle. SCAR-5, an exploratory score derived from routine pretreatment laboratory values, stratified risk of early treatment attrition; external prospective validation is required before clinical use.