帕博利珠单抗治疗转移性尿路上皮癌患者中放射学肿瘤负荷的预后影响

Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab.

作者信息

Katayama Satoshi, Iwata Takehiro, Kawada Tasushi, Okamoto Yusuke, Sano Yuho, Kawago Yuya, Miyake Shuji, Moriwake Takatoshi, Kuinose Aya, Horikawa Yuhei, Tsuboi Kazuma, Tsuboi Ichiro, Sakaeda Kazuma, Nakatsuka Hirokazu, Takamoto Atsushi, Hirata Takeshi, Shirasaki Yoshinori, Yamasaki Taku, Morinaka Hirofumi, Nagasaki Naoya, Hara Takafumi, Ochi Akinori, Okumura Misa, Watanabe Tomofumi, Sekito Takanori, Kawano Kaoru, Horii Satoshi, Yamanoi Tomoaki, Nagao Kentaro, Yoshinaga Kasumi, Maruyama Yuki, Tominaga Yusuke, Sadahira Takuya, Nishimura Shingo, Edamura Kohei, Kobayashi Tomoko, Kusumi Norihiro, Kurose Kyohei, Yamamoto Yasuo, Sugimoto Morito, Nakada Tetsuya, Sasaki Katsumi, Takenaka Tadasu, Ebara Shin, Miyaji Yoshiyuki, Wada Koichiro, Kobayashi Yasuyuki, Araki Motoo

机构信息

Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Department of Urology, Fukuyama City Hospital, Hiroshima, Japan.

出版信息

Urol Oncol. 2024 Mar;42(3):70.e11-70.e18. doi: 10.1016/j.urolonc.2023.11.009. Epub 2023 Dec 20.

DOI:10.1016/j.urolonc.2023.11.009

PMID:38129282

Abstract

PURPOSE

Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC.

METHODS

We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines.

RESULTS

Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses.

CONCLUSION

Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.

摘要

目的

在免疫治疗时代，放射学肿瘤负荷已被报道在多种恶性肿瘤中具有预后价值，但在接受帕博利珠单抗治疗的转移性尿路上皮癌（mUC）患者中，其是否具有预后价值仍未得到研究。我们旨在评估mUC患者放射学肿瘤负荷的预测和预后价值。

方法

我们对308例接受帕博利珠单抗治疗的mUC患者进行了回顾性分析。放射学肿瘤负荷由基线肿瘤大小（BTS）和基线肿瘤数量（BTN）表示。使用约登指数将BTS的最佳截断值确定为50 mm（小BTS：n = 194，大BTS：n = 114）。比较总生存期（OS）、癌症特异性生存期（CSS）、无进展生存期（PFS）和客观缓解率（ORR）。使用受限立方样条评估BTS与OS和CSS之间的非线性关联。

结果

大BTS患者原发肿瘤接受手术切除的可能性较小（P = 0.01），发生肝转移的可能性较大（P < 0.001），转移病灶较多（P < 0.001）。在控制混杂因素（原发肿瘤切除、转移部位、转移灶数量和乳酸脱氢酶水平）影响的多变量分析中，大BTS和高BTN分别与较差的OS（HR 1.52；P = 0.015，以及HR 1.69；P = 0.018）和CSS（HR 1.59；P = 0.01，以及HR 1.66；P = 0.031）独立相关，但与PFS无关。受限立方样条显示BTS与OS和CSS呈线性相关。此外，在单变量分析中，大BTS显著预测较低的ORR和完全缓解率（分别为P = 0.041和P = 0.032），但其关联在多变量分析中消失。