Umeda Kota, Tanaka Nobuyuki, Yasumizu Yota, Takeda Toshikazu, Matsumoto Kazuhiro, Morita Shinya, Kosaka Takeo, Mizuno Ryuichi, Oya Mototsugu
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Clin Genitourin Cancer. 2023 Feb;21(1):128-135. doi: 10.1016/j.clgc.2022.08.004. Epub 2022 Aug 7.
Since tumors in different human organs may have different tumor microenvironments, we evaluate time-course changes in all tumor locations after pembrolizumab treatment in urothelial carcinoma (UC) to examine the differences in efficacy of pembrolizumab per organ. Further, we uncover the usefulness of inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), CRP, and kinetics of these markers to predict pembrolizumab success and relation to overall survival (OS) in UC.
A total of 115 cancerous lesions from 44 UC patients were measurable based on RECIST 1.1 criteria. The serum CRP and NLR levels were measured at baseline prior to pembrolizumab treatment and at least every 3 weeks just prior to pembrolizumab administration.
Site-specific success (ie, patients with CR/PR/SD by RESIST 1.1) rates for pembrolizumab treatments were as follows: primary tumors: 67%, lymph node: 70%, lung: 44%, liver: 40%, and peritoneal metastasis: 56%. Focusing on the major metastasis sites, lymph nodes and lungs, we examined the relationships between NLR, CRP, or that kinetics and pembrolizumab success. In lymph nodes, both early NLR kinetics (P = .005) and CRP kinetics (P = .035) was a predictor for pembrolizumab success. On the other hand, none of 4 was not in lung metastases. Regarding to the mortality, the multivariate analysis revealed that early NLR kinetics was a prognostic biomarker for OS among the 4, independent of performance status and liver metastasis.
We revealed that site-specific pembrolizumab success in UC. Early NLR kinetics was a predictor for lymph node pembrolizumab success and OS in our cohorts.
由于不同人体器官中的肿瘤可能具有不同的肿瘤微环境，我们评估了帕博利珠单抗治疗尿路上皮癌（UC）后所有肿瘤部位的时间进程变化，以研究帕博利珠单抗在每个器官中的疗效差异。此外，我们还揭示了中性粒细胞与淋巴细胞比率（NLR）、CRP等炎症标志物的作用及其动力学变化，以预测帕博利珠单抗治疗UC的疗效以及与总生存期（OS）的关系。
根据RECIST 1.1标准，44例UC患者共115个癌灶可测量。在帕博利珠单抗治疗前的基线期以及每次帕博利珠单抗给药前至少每3周测量血清CRP和NLR水平。
帕博利珠单抗治疗的部位特异性缓解率（即根据RECIST 1.1标准达到CR/PR/SD的患者）如下：原发肿瘤：67%，淋巴结：70%，肺：44%，肝：40%，腹膜转移：56%。聚焦于主要转移部位淋巴结和肺，我们研究了NLR、CRP或其动力学变化与帕博利珠单抗疗效之间的关系。在淋巴结中，早期NLR动力学变化（P = 0.005）和CRP动力学变化（P = 0.035）均是帕博利珠单抗疗效的预测指标。另一方面，在肺转移灶中这4项指标均无预测作用。关于死亡率，多变量分析显示，早期NLR动力学变化是这4项指标中OS的预后生物标志物，与体能状态和肝转移无关。
我们揭示了帕博利珠单抗治疗UC存在部位特异性疗效差异。在我们的队列中，早期NLR动力学变化是淋巴结中帕博利珠单抗疗效及OS的预测指标。
