Muniz Miguel, Sartor Oliver, Orme Jacob J, Koch Regina M, Rosenow Hana R, Mahmoud Ahmed M, Andrews Jack R, Kase Adam M, Riaz Irbaz B, Belge Bilgin Gokce, Thorpe Matthew P, Kendi A Tuba, Johnson Geoffrey B, Ravi Praful, Kwon Eugene D, Childs Daniel S
Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota;
Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
J Nucl Med. 2024 Dec 3;65(12):1932-1938. doi: 10.2967/jnumed.124.268277.
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 [Lu]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. 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 χ 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. 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], = 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, < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; < 0.001). 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为短暂反应。关于[镥]镥-PSMA-617（LuPSMA）治疗后结局的数据很少。VISION试验报告了肝转移亚组患者总生存期（OS）的风险比，但未披露绝对生存时长。利用真实世界临床数据，我们研究了这一重要亚组患者，描述了前列腺特异性抗原（PSA）反应和总生存期。收集了明尼苏达州罗切斯特市梅奥诊所所有在2022年3月至2023年3月期间开始接受LuPSMA治疗患者的单机构数据库。提取了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检查有无肝转移对患者进行分类。分别采用χ检验和Kaplan-Meier方法比较两组（有肝转移组与无肝转移组）的PSA反应和总生存期。进行了多变量Cox回归分析，纳入既定的预后因素。最后，对通过83基因检测板检测出治疗前循环肿瘤DNA的患者评估有无致病性和可能致病性改变。使用描述性统计总结这些发现，并使用Fisher精确检验在两个队列之间进行比较。整个队列由273例患者组成，其中43例（15.75%）在治疗前PSMA PET/CT检查时有肝转移。有肝转移患者接受的中位周期数为3（范围1 - 6），无肝转移患者为5（范围1 - 6）。有肝转移患者PSA从基线反应率降低50%或更多的比例低于无肝转移患者（30.23%[13/43]对49.77%[106/213]；P = 0.019）。中位随访10个月（四分位间距9 - 13个月）时，中位总生存期有显著差异（8.35个月对未达到，P < 0.001）。多变量分析显示肝转移的存在与较短生存期独立相关（风险比4.06；P < 0.001）。我们的数据表明，肝转移的存在预示着接受LuPSMA治疗患者的结局较差。应探索替代和联合方法，以最大化放射性药物治疗在肝脏中的抗肿瘤活性。
