Park Young Joo, Lee Chan Ho, Seo Won Ik, Chung Jae Il, Ku Ja Yoon, Kim Kyung Hwan, Kang Byeong Jin, Ha Hong Koo
Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan 49241, Republic of Korea.
Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea.
Oncol Lett. 2025 Mar 4;29(4):211. doi: 10.3892/ol.2025.14957. eCollection 2025 Apr.
The present study aimed to evaluate the incidence, characteristics and management of hepatic immune-related adverse events (irAEs) in patients with advanced or metastatic urothelial carcinoma (UC) and renal cell carcinoma (RCC) receiving immune checkpoint inhibitors (ICIs). Data regarding the demographics, ICI regimens and hepatic irAEs from 213 patients with metastatic UC or metastatic RCC receiving ICIs between February 2018 and September 2023 at three tertiary medical centers (Inje University Busan Paik Hospital, Busan, South Korea; Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan, South Korea; Pusan National University Hospital, Busan, South Korea) in South Korea were collected and retrospectively analyzed. Hepatic irAEs were graded using the Common Terminology Criteria for Adverse Events version 5.0 and classified based on R value patterns. Among the 213 patients evaluated, 76 (35.6%) experienced at least one irAE, whereas 48 (22.5%) developed hepatic irAEs. The median onset time for hepatic irAEs was 6.5 weeks, with incidence rates being higher with combination therapies than with monotherapies (31.8 vs. 18.3%; P=0.014). Furthermore, 72.9 and 27.1% of the patients had grade 1-2 and 3-4 hepatic irAEs, respectively. The patterns of liver toxicity included cholestatic (35.4%), mixed (35.4%) and hepatocellular (29.2%). All patients with grade 1-2 hepatic irAE recovered with supportive treatment without ICI discontinuation or corticosteroids use. Among the 13 patients with grade ≥3 hepatic irAEs, 12 recovered with high-dose corticosteroids, while 1 died due to fulminant hepatitis. Hepatic irAEs are common in patients with advanced and metastatic urologic cancers who are treated with ICIs, particularly with combination therapies. Most cases have low-grade irAE that are manageable without ICI discontinuation; however, severe cases require prompt recognition and treatment with corticosteroids. These findings emphasize the importance of regular liver function monitoring and appropriate management strategies for hepatic irAEs in patients with urologic cancer receiving ICI therapy.
本研究旨在评估接受免疫检查点抑制剂（ICI）治疗的晚期或转移性尿路上皮癌（UC）和肾细胞癌（RCC）患者肝免疫相关不良事件（irAE）的发生率、特征及管理情况。收集了2018年2月至2023年9月期间在韩国三家三级医疗中心（韩国釜山仁济大学白医院；韩国釜山东南放射医学科学癌症中心；韩国釜山国立大学医院）接受ICI治疗的213例转移性UC或转移性RCC患者的人口统计学数据、ICI治疗方案及肝irAE情况，并进行回顾性分析。肝irAE采用《不良事件通用术语标准》第5.0版进行分级，并根据R值模式进行分类。在评估的213例患者中，76例（35.6%）经历了至少一次irAE，48例（22.5%）发生了肝irAE。肝irAE的中位发病时间为6.5周，联合治疗的发生率高于单药治疗（31.8%对18.3%；P=0.014）。此外，72.9%和27.1%的患者分别发生1-2级和3-4级肝irAE。肝毒性模式包括胆汁淤积型（35.4%）、混合型（35.4%）和肝细胞型（29.2%）。所有1-2级肝irAE患者经支持治疗后恢复，未停用ICI或使用糖皮质激素。在13例≥3级肝irAE患者中，12例经大剂量糖皮质激素治疗后恢复，1例因暴发性肝炎死亡。肝irAE在接受ICI治疗的晚期和转移性泌尿系统癌症患者中很常见，尤其是联合治疗时。大多数病例为低级别irAE，无需停用ICI即可处理；然而，严重病例需要及时识别并使用糖皮质激素治疗。这些发现强调了在接受ICI治疗的泌尿系统癌症患者中定期监测肝功能及对肝irAE采取适当管理策略的重要性。
