Radioligand treatment with [177Lu]Lu-PSMA I&T in elderly Patients – Safety, efficacy, and prognostic factors for survival

Eur J Nucl Med Mol Imaging. 2025 Aug 25. doi: 10.1007/s00259-025-07519-1. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to evaluate the safety and efficacy to explore predictors of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA I&T in metastatic castration-resistant prostate cancer (mCRPC) patients aged ≥ 75 and explored baseline predictors of overall survival (OS).

MATERIALS AND METHODS: 56 men (median age 78, range 75-95) were treated with RLT. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Baseline Gleason score, blood parameters (PSA, LDH), and sites of metastases (bone, lymph nodes, liver, lung) were recorded. Quantitative PET parameters such as SUVmean (mean standardized uptake value), SUVpeak (peak standardized uptake value), SUVmax (maximum standardized uptake value), PSMA-TV (PSMApositive tumor volume), TL-PSMA (total lesion PSMA) were measured. PET response was assessed by RECIP 1.0 (response evaluation criteria in PSMA imaging); biochemical response by PCWG3 (prostate cancer working group 3). Associations with OS were analyzed via uni- and multivariable Cox regression and Kaplan-Meier curves.

RESULTS: No CTCAE grade III-V toxicities occurred. Grade I/II hematologic events included anemia (23.2%), leukocytopenia (18.6%) and thrombocytopenia (9.3%); eGFR declined by 2.5% (grade I/II in 18.6%). Median OS was 11 months; 60.7% of patients died. 74.4% of patients (32/43) showed PSA declines (median – 58%; 14/43 ≥ 50%). Higher baseline PSA (HR 1.001 per ng/mL; P < 0.10) and LDH (HR 1.008 per U/L; P < 0.01) were associated with shorter OS. Patients with progressive disease by both RECIP and PCWG3 had shorter OS than others (11 vs. 22 months; HR 3.3; P < 0.01). Any PSA response predicted longer OS (21 vs. 7 months; HR 0.3; P < 0.01). Presence of liver metastases portended poorer survival (8 vs. 21 months; HR 6.7; P < 0.001).

CONCLUSION: [¹⁷⁷Lu]Lu-PSMA I&T RLT is well tolerated in patients ≥ 75 years. Lower baseline PSA and LDH but not PSMA-TV predict longer OS. Early PSA response strongly correlates with improved survival. Combined use of RECIP and PCWG3 criteria optimizes response assessment.

PMID:40851054 | DOI:10.1007/s00259-025-07519-1