Prognostic Impact of Liver Metastases on [177Lu]Lu-Psma Therapy Outcomes in Metastatic Castration-Resistant Prostate Cancer Publisher



Shamshirgaran A ; Samadi MH ; Sahafi P ; Aboutalebi F ; Roustaei H ; Shafiei S ; Aryana K ; Aghaee A ; Barashki S ; Harsini S ; Askari E
Source: Nuclear Medicine and Molecular Imaging Published:2026

Abstract

Purpose: This study assessed the efficacy, safety, and laboratory changes of lutetium-177 [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC) patients with liver metastasis. Methods: Retrospective cohort of 208 mCRPC patients stratified by baseline liver metastasis status. Eligibility required confirmed mCRPC, PSMA-avid lesions confirmed by [⁹⁹ᵐTc]Tc-HYNIC-PSMA single-photon emission computed tomography (SPECT/CT) or [⁶⁸Ga]Ga-PSMA-11 positron emission tomography–computed tomography (PET/CT), and Eastern Cooperative Oncology Group (ECOG) score of 0–2. Liver metastases were identified via contrast-enhanced CT, magnetic resonance imaging (MRI) or [68 Ga]Ga-PSMA PET/CT. Primary endpoints: overall survival (OS) and PSA progression-free survival (PSA-PFS). Secondary endpoints: PSA50 response rate (≥ 50.0% PSA decline), laboratory trends, and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 toxicities. Comparisons used Mann–Whitney, Fisher’s exact, and t-tests. Survival estimated via Kaplan–Meier, parameter changes via analysis of variance (ANOVA), and prognostic factors via Cox regression. Analyses performed in R (v4.2.2) with p < 0.05 considered as significant. Results: Twenty-five patients (12.0%) had liver metastases. Median follow-up: 9.0 months (95% confidence interval [CI]: 7–11). Cohort median OS: 14.0 months (95% CI: 12–20). Liver metastases group showed shorter OS (6.0 vs 18.0 months, p < 0.001) and independent prognostic impact (hazard ratio [HR] = 2.53, 95% CI: 1.41–4.55, p = 0.002). Median PSA-PFS: 7.0 months overall, shorter with liver metastases (3.25 vs 8.0 months). PSA50 response: 50.8% overall, similar between groups (47.0% vs 51.4%). Grade 3–4 hematologic/renal toxicities were rare and comparable across subgroups. Conclusion: Liver metastases strongly predict worse survival and shorter biochemical control in mCRPC patients treated with [177Lu]Lu-PSMA-617. Nevertheless, approximately 50.0% of liver-metastatic patients achieved clinically meaningful PSA responses, and the treatment was well tolerated with low severe toxicity. Results indicate visceral disease primarily impacts efficacy rather than safety, supporting ongoing use of [177Lu]Lu-PSMA-617 in this population. © The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2026.