Baseline clinical characteristics predict overall survival in patients undergoing radioligand therapy with [¹⁷⁷Lu]Lu-PSMA I&T during long-term follow-up

Background: Radioligand therapy (RLT) with ¹⁷⁷Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [¹⁷⁷Lu]Lu-PSMA I&T RLT in a long-term follow-up.

Materials and methods: Ninety-two mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (interval_{Diagnosis-RLT}, per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan-Meier analyses.

Results: Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02-1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01-1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06-1.26; P = 0.001), and interval_{Diagnosis-RLT} (HR, 0.95, 95% CI 0.91-0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and interval_{Diagnosis-RLT}, 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan-Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged interval_{Diagnosis-RLT} (P ≤ 0.01, respectively).

Conclusion: In mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [¹⁷⁷Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.