# Impact of Peri-Immunotherapy Antibiotic Exposure on Survival Outcomes in Metastatic Renal Cell Carcinoma: A Real-World IMDC Risk–Stratified Analysis

## TL;DR

Using antibiotics around the time of immunotherapy treatment for kidney cancer is linked to worse survival outcomes, especially for patients with intermediate or poor risk profiles.

## Contribution

This study is the first to show that antibiotic use near immunotherapy initiation worsens outcomes in metastatic renal cell carcinoma patients stratified by IMDC risk.

## Key findings

- Antibiotic exposure was associated with significantly shorter progression-free and overall survival in RCC patients receiving immunotherapy.
- Antibiotic use remained an independent predictor of worse survival outcomes, even after adjusting for other factors.
- Intermediate- and poor-risk patients experienced the most pronounced survival declines with antibiotic exposure.

## Abstract

Background: Antibiotic exposure has been shown to negatively affect immune checkpoint inhibitor (ICI) efficacy in several cancers, possibly by disrupting gut microbiota. It represents a potentially modifiable clinical factor that may influence immunotherapy efficacy in RCC. However, data on renal cell carcinoma (RCC) remain limited, especially regarding prognostic risk groups. Methods: We conducted a retrospective cohort study of 120 RCC patients treated with ICIs between 2018 and 2024 at Kartal Dr. Lütfi Kırdar City Hospital. Patients were classified based on systemic antibiotic exposure within ±30 days of ICI start. Survival outcomes were compared using Kaplan–Meier and Cox regression analyses. Subgroup analyses were performed according to the International Metastatic RCC Database Consortium (IMDC) risk classification. Results: Of the 120 patients, 38 (31.7%) received antibiotics during the peri-ICI period. Median progression-free survival (PFS) was significantly shorter in the antibiotic-exposed group (5.1 vs. 9.4 months; p = 0.004), as was overall survival (OS) (14.8 vs. 22.5 months; p = 0.03). Antibiotic use remained an independent predictor of both PFS (HR = 1.87; 95% CI: 1.21–2.89) and OS (HR = 1.64; 95% CI: 1.04–2.59). In subgroup analyses, intermediate-risk patients had worse OS with antibiotics (13.5 vs. 20.6 months; p = 0.035), as did poor-risk patients (8.1 vs. 13.9 months; p = 0.049). Conclusions: Antibiotic exposure during the peri-immunotherapy period is linked to significantly poorer outcomes in RCC patients, especially those with intermediate and poor IMDC risk scores. These findings emphasize the importance of antimicrobial stewardship and suggest a potential role for microbiome-informed patient management in RCC.