Incidence and management of hepatic immune‑related adverse events in advanced urologic cancers treated with immune checkpoint inhibitors: A multicenter retrospective study.

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.