Efficacy and safety of ¹⁷⁷Lu-PSMA radioligand therapy: A real-world study

Objective: To evaluate the effectiveness and safety of 177Lu-PSMA radioligand therapy (RLT) in patients with disseminated prostate cancer who were followed up in healthcare institutions of the Moscow Department of Health and received treatment outside of clinical trials.Materials and methods: This retrospective study included patients with disseminated prostate cancer treated with 177Lu-PSMA RLT and followed up at outpatient oncology centers in Moscow between January 1, 2022, and December 1, 2025. Inclusion criteria: histologically verified prostate adenocarcinoma, radiological signs of metastatic disease, and treatment with at least 1 cycle of 177Lu-PSMA RLT. Exclusion criteria: absence of data on ≥ 1 177Lu-PSMA administration and ≥ 1 follow-up examination after treatment initiation. The primary endpoint was radiologic progression-free survival (rPFS). The secondary endpoints included the PSA50 response rate (defined as a ≥ 50 % decline in prostate-specific antigen from baseline), PSA progression-free survival (PSA-PFS), progression-free survival according to the Prostate Cancer Working Group 3 criteria (PFSPCWG3), overall survival (OS), time to clinical deterioration, safety, and toxicity.Results: A total of 41 patients were included in the analysis. The median age was 72 years (range: 53-85). At RLT initiation (baseline), 9 patients (21.9 %) had ECOG PS scores of 2-3. Twenty-nine patients (70.7 %) had been previously treated with ≥ 1 taxane and ≥ 1 androgen receptor signaling inhibitor (ARSI). Castration resistance prior to RLT initiation was observed in 40 patients (97.6 %). The median baseline PSA level was 121.7 ng / mL (range: 0.6-4987.7). All patients had PSMA-positive metastases; in 3 cases (7.3 %), these were accompanied by clinically significant PSMA-negative metastases. All patients received 177Lu-PSMA RLT (median of 4 cycles [range, 1-8]). Forty patients (97.6 %) received RLT concomitantly with continuous androgen deprivation therapy (ADT); 11 patients (26.8 %) received RLT during ADT in combination with an ARSI; 3 patients (7.3 %) underwent combined systemic radiopharmaceutical therapy (2 patients [4.9 %] with 177Lu-PSMA / 153Sm, and 1 patient [2.4 %] with 177Lu-PSMA / 225Ac-PSMA). The median follow-up duration was 10 months (range: 0.4-30). The PSA50 response rate was 46.3 %, median rPFS was 6.2 months (95 % confidence interval [CI], 4.7-7.7), median PSA-PFS was 5.2 months (95 % CI, 2.7-7.7), median PFSPCWG3 was 5.7 months (95 % CI, 4.8-6.5), median OS was 11.4 months (95 % CI, 6.2-16.6), and median time to clinical deterioration was 5.8 months (95 % CI, 3.9-7.8). Serious AEs were reported in 18 patients (43.9 %), AE-related RLT discontinuation was required in 8 cases (19.5 %), and AE-related death was reported in 3 cases (7.3 %). Grade 3-4 anemia developed in 15 patients (36.6 %), grade 3-4 thrombocytopenia in 14 patients (34.1 %), and neutropenia in 17 patients (41.5 %).Conclusion: Data from real-world clinical practice confirm the effectiveness of 177Lu-PSMA RLT in patients with disseminated prostate cancer. However, the safety profile raises significant concern. These findings highlight the need for a more balanced approach to patient selection for RLT.