Upper Tract Urothelial Carcinoma (UTUC) is notably more prevalent in Taiwan, where it accounts for a significant proportion of urothelial tumors. Current evidence suggests a potential association between air pollution, including PM2.5, and the risk of urothelial cancers, with stronger data supporting mortality outcomes in bladder cancer. However, due to methodological constraints and limited data, particularly for UTUC, the relationship remains inadequately studied. This study aims to investigate the relationship between PM2.5 exposure and clinical outcomes in patients with UTUC.

Between January 2017 and December 2022, patients with UTUC who underwent nephroureterectomy were identified from a multicenter UTUC registry database, as part of the Taiwan UTUC Collaboration Group. To account for temporal and geographic variability in ambient PM2.5 concentrations, individual exposure levels were defined as the 5-year average PM2.5 concentration at each patient’s residential location, calculated for the period preceding their year of diagnosis. PM2.5 data were obtained from the Ministry of Environment’s air quality monitoring system. The cutoff point for PM 2.5 concentration is set as mean value of exposure of this UTUC group.

A total of 404 patients were included in this study, with a median age of 70 years. Based on the mean value, patients were stratified into two groups: the High PM2.5 Exposure group (n = 223, >22.89 μg/m³) and the Low PM2.5 Exposure group (≤22.89 μg/m³). Patients in the Low PM2.5 Exposure group had significantly higher pathological T and N stages, as well as increased mortality rates . In univariable analysis, younger age, lower PM2.5 exposure, higher pathological T stage, and lymphovascular invasion (LVI) were all associated with increased risks of distant metastasis and overall mortality. Interestingly, Kaplan–Meier survival analysis (Figure 1) revealed that patients in the High PM2.5 Exposure group demonstrated significantly better outcomes in terms of distant metastasis (p = 0.020) and overall mortality (p = 0.038), contrary to initial expectations. However, after adjusting for age, pathological T stage, and LVI in the multivariable analysis, PM2.5 was no longer a significant independent predictor of outcome (95% HR 0.353-1.197, p=0.166).

In this multicenter cohort, UTUC patients exposed to higher ambient PM2.5 levels had lower pathological T stages, reduced rates of distant metastasis, and improved overall survival. These findings may reflect earlier diagnosis in more polluted areas, potentially due to better healthcare accessibility, rather than indicating a direct effect of PM2.5 exposure on disease progression. Further studies are warranted to clarify the impact of air pollution on UTUC outcomes.