It is well known that patients with liver metastasis from metastatic castration-resistant prostate cancer have poor or only transient responses to many forms of systemic therapy. Data on outcomes after treatment with [¹⁷⁷Lu]Lu-PSMA-617 (LuPSMA) are scarce. The VISION trial reports a hazard ratio for overall survival (OS) in the subgroup of patients with liver metastasis without disclosing the absolute duration of survival. Using real-world clinical data, we examined this important subgroup of patients, describing prostate-specific antigen (PSA) response and OS. Methods: A single-institution database was assembled to include all patients receiving LuPSMA at Mayo Clinic in Rochester, Minnesota, for whom treatment was initiated between March 2022 and March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were then categorized by presence or absence of liver metastasis on pretreatment prostate-specific membrane antigen (PSMA) PET. PSA response and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ² testing and the Kaplan–Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Finally, those with pretreatment circulating tumor DNA as determined in an 83-gene panel were assessed for the presence of pathogenic and likely pathogenic alterations. These findings were summarized using descriptive statistics and compared between the 2 cohorts using the Fisher exact test. Results: The overall cohort consisted of 273 patients, including 43 (15.75%) with liver metastasis on pretreatment PSMA PET/CT. The median number of cycles received was 3 (range, 1–6) for patients with liver metastasis and 5 (range, 1–6) for those without hepatic involvement. The 50% or greater reduction in PSA from baseline response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs 49.77% [106/213], P = 0.019). At a median follow-up of 10 mo (interquartile range, 9–13 mo), there was a significant difference in median OS (8.35 mo vs. not reached, P < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; P < 0.001). Conclusion: Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment. Alternative and combination approaches should be explored to maximize the antitumor activity of radiopharmaceutical therapy in the liver.

众所周知，转移性去势抵抗性前列腺癌肝转移患者对多种形式的全身治疗反应不佳或仅一过性反应。关于 [¹⁷⁷Lu]Lu-PSMA-617 （LuPSMA） 治疗后结局的数据很少。VISION 试验报告了肝转移患者亚组的总生存期 （OS） 风险比，但没有披露绝对生存期。使用真实世界的临床数据，我们检查了这一重要的患者亚组，描述了前列腺特异性抗原 （PSA） 反应和 OS。方法： 组装了一个单一机构数据库，包括在明尼苏达州罗切斯特市梅奥诊所接受 LuPSMA 的所有患者，这些患者在 2022 年 3 月至 2023 年 3 月期间开始治疗。提取基线临床病理和影像学特征。然后根据治疗前前列腺特异性膜抗原 （PSMA） PET 上是否存在肝转移对患者进行分类。分别使用 χ² 检验和 Kaplan-Meier 方法比较 2 组 （肝转移与无肝转移） 的 PSA 反应和 OS。进行多变量 Cox 回归分析，包括已确定的预后因素。最后，评估那些在 83 基因组中确定的治疗前循环肿瘤 DNA 的人是否存在致病性和可能的致病性改变。使用描述性统计对这些发现进行总结，并使用 Fisher 精确检验在 2 个队列之间进行比较。结果：整个队列由 273 例患者组成，其中 43 例 （15.75%） 治疗前 PSMA PET/CT 有肝转移。 肝转移患者接受的中位周期数为 3 （范围，1-6），无肝脏受累的患者为 5 （范围，1-6）。肝转移患者 PSA 较基线缓解率降低 50% 或以上低于无肝转移患者 （30.23% [13/43] vs 49.77% [106/213]，P = 0.019）。在中位随访 10 个月 （四分位距，9-13 个月） 时，中位 OS 存在显著差异 （8.35 个月 vs. 未达到，P < 0.001）。在多变量分析中，肝转移的存在与较短的生存期独立相关 （风险比，4.06;P < 0.001）。结论：我们的数据表明，肝转移的存在预示着接受 LuPSMA 治疗的患者预后较差。应探索替代和联合方法，以最大限度地提高放射性药物治疗在肝脏中的抗肿瘤活性。