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

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 < 0.05). The five-item Single-Cycle Attrition Risk (SCAR-5) score (one point each: CRP ≥ 16.5 mg/L, lymphocytes ≤ 1.39 × 109/L, hemoglobin ≤ 9.6 g/dL, ALP ≥ 191 U/L, PSA ≥ 34.2 ng/mL) discriminated SCA with an optimism-corrected area under the ROC curve (AUC) of 0.88 (apparent AUC 0.95, 95% confidence interval (CI) 0.89–0.99). No SCA occurred below score 3 (0/39; upper 95% confidence limit 9.0%); a score ≥ 3 identified all events (sensitivity 100%, 95% CI 74–100; specificity 85%, 95% CI 71–94) and was associated with shorter survival (univariable Cox hazard ratio 3.94, 95% CI 2.01–7.74). 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.