Age-Related Outcomes of [177Lu]Lu-PSMA Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer: A Retrospective Analysis

<b>Background/Objectives:</b> To investigate the efficacy and safety of treatment with [¹⁷⁷Lu]Lu-PSMA-I&T Radioligand Therapy (PSMA-RLT) in older patients (≥80 years) vs. younger ones with metastatic castration-resistant prostate cancer (mCRPC). <b>Methods:</b> In this retrospective single-center analysis, 103 patients treated with PSMA-RLT between 2019 and 2024 were included. Overall survival (OS) and therapeutic response were assessed by PSA serum and based on PET/CT Imaging according to the RECIP 1.0 criteria, respectively. Toxicity was additionally assessed via laboratory (hemoglobin, cell counts, and serum creatinine). Adverse events (AEs) were detected according to CTCAE V.5. <b>Results:</b> Median OS did not differ significantly in patients ≥ 80 years vs. <80 years (13.7 vs. 16.1 months, respectively). PSA decline of ≥50% was achieved in 32% patients in total, comparably in both groups (29.4% vs. 34.8%). According to RECIP 1.0, the majority of patients with both ≥80 and <80 years demonstrated stable disease or partial responses in imaging (64% and 71%, post two cycles). Concerning toxicity, the most frequently observed AE was anemia, which occurred in both <80 and ≥80 subgroups (grade 3: 2.8% vs. 5.9%); however, no grade 4 anemia was recorded. Renal function remained stable throughout treatment, and no AE grade 3 or higher was observed. Overall, the safety profile was comparable between age groups. <b>Conclusions:</b> Treatment with PSMA-RLT can be both effective and well tolerated in patients with mCRPC aged 80 years and older.