Kobayashi Takashi, Ito Katsuhiro, Kojima Takahiro, Kato Minoru, Kanda Souhei, Hatakeyama Shingo, Matsui Yoshiyuki, Matsushita Yuto, Naito Sei, Shiga Masanobu, Miyake Makito, Muro Yusuke, Nakanishi Shotaro, Kato Yoichiro, Shibuya Tadamasa, Hayashi Tetsutaro, Yasumoto Hiroaki, Yoshida Takashi, Uemura Motohide, Taoka Rikiya, Kamiyama Manabu, Ogawa Osamu, Kitamura Hiroshi, Nishiyama Hiroyuki
Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan.
Cancer Sci. 2021 Feb;112(2):760-773. doi: 10.1111/cas.14762. Epub 2020 Dec 21.
The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil-to-lymphocyte ratio. The median OS times (95% confidence intervals [CIs]) for the low-, intermediate-, and high-risk groups (discovery cohort) were not yet reached (NYR) (NYR-19.1), 6.8 mo (5.8-8.9), and 2.3 mo (1.2-2.6), respectively. The HRs (95% CI) for OS in the low- and intermediate-risk groups vs the high-risk group were 0.07 (0.04-0.11) and 0.23 (0.15-0.37), respectively. The objective response rates for in the low-, intermediate-, and high-risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first-line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab-treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design.
免疫检查点抑制剂用于治疗尿路上皮癌（UC）的情况正在迅速增加，但对于经过验证的风险分层尚无明确指导。这项多中心回顾性研究收集了463例患者的临床病理信息，并对11个预先定义的变量进行分析，以建立一个预测总生存期（OS）的多变量模型。该模型使用292例患者的独立数据集进行验证。发现队列和验证队列之间的患者特征和结局平衡良好，发现队列和验证队列的中位OS时间分别为10.2个月和12.5个月。最终经过验证的多变量模型由基于独立预后因素（包括体能状态、转移部位、血红蛋白水平和中性粒细胞与淋巴细胞比值）的风险比（HR）得出的风险评分定义。低、中、高风险组（发现队列）的中位OS时间（95%置信区间[CI]）分别为未达到（NYR）（NYR - 19.1）、6.8个月（5.8 - 8.9）和2.3个月（1.2 - 2.6）。低风险组和中风险组与高风险组相比的OS的HR（95%CI）分别为0.07（0.04 - 0.11）和0.23（0.15 - 0.37）。低、中、高风险组的客观缓解率分别为48.3%、28.8%和10.5%。这些不同的结局在验证队列以及围手术期或一线化疗后接受帕博利珠单抗治疗的患者（N = 584）中得到了很好的重现。总之，本研究建立并验证了一个简单的预后模型，用于预测帕博利珠单抗治疗的化疗耐药UC患者的肿瘤学结局。该模型为外部验证、患者咨询和临床试验设计提供了有用信息。
