# Single-center experience with immune checkpoint inhibitor-related ureteritis and cystitis

## TL;DR

This study examines a rare side effect of cancer immunotherapy drugs, focusing on symptoms, diagnosis, and treatment of ureteritis and cystitis.

## Contribution

The study introduces a severity grading system and explores JAK inhibitors as a treatment for steroid-dependent cases of ICI-related ureteritis and cystitis.

## Key findings

- ICI-related ureteritis and cystitis occurred in 0.96% of patients treated with immune checkpoint inhibitors.
- Imaging features like hydroureteronephrosis and ureteral wall thickening were consistently observed in diagnosed cases.
- JAK inhibitors showed therapeutic potential in patients who failed steroid tapering.

## Abstract

Ureteritis and cystitis is a rare immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), challenging to distinguish from urinary tract infection (UTI), easily leading to missed diagnosis. We aim to describe clinical features, radiological characteristics and treatment of patients who suffer from ICI-related ureteritis and cystitis (ICI-UC).

This was a single centre case series of patients diagnosed with solid tumor who received ICIs treatment and subsequently suffered from ICI-UC. All clinical demographic data, laboratory parameters, imaging characteristics, and treatment information were collected.

Between Mar 1st, 2020 and Mar 31th 2025, 12 of 1239 patients treated at Peking Union Medical College Hospital with ICIs were confirmed to have ICI-related ureteritis and cystitis (0.96%), 10 males and 2 females. Only 1 patient received anti-programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) dual immunotherapy, the other 11 patients received PD-1/PD-ligand 1 plus chemotherapy or/and target therapy. The median time to onset was 83 days (range 28–442 days). All patients (100%) exhibited significant urinary tract irritation symptoms. 12 patients demonstrated characteristic imaging abnormalities, including hydroureteronephrosis, irregular ureteral wall thickening, bladder wall thickening with irregular margins, or/and conspicuous renal fascia. Spontaneous remission was observed in 2 patients, while 10 patients received steroids and all showed rapid improvement of symptom after treatment.The median time from symptom onset to the initiation of steroids was 24 days, and the median prednisone dose was 0.60 mg/kg/day. Six patients (6/10, 60%) experienced disease recurrence during the corticosteroid tapering phase, and two patients who failed steroid tapering were successfully treated with a combination of corticosteroid and JAK inhibitor therapy.

This pioneering cohort study provides the first systematic investigation of ICI-UC, establishing its incidence and comprehensively characterizing clinical and imaging features. Through cohort analysis, we propose a novel severity grading system with corresponding treatment algorithms, while additionally exploring the therapeutic potential of JAK inhibitors for steroid-dependent cases.