In cancer, tumor‑related inflammation affects disease progression and survival outcomes. However, the role of systemic inflammation in tumor multifocality in upper tract urothelial carcinoma (UTUC) is not well understood. The aim of the present study was to evaluate the impact of the systemic inflammation response index (SIRI) on tumor multifocality for predicting oncological outcomes in patients with UTUC after radical nephroureterectomy (RNU). For this purpose, data from 645 patients with non‑metastatic UTUC who underwent RNU between 2008 and 2020 were retrospectively analyzed. Survival outcomes such as overall survival (OS), cancer‑specific survival (CSS) and recurrence‑free survival (RFS) RATES were assessed using the Kaplan‑Meier method, and independent prognostic factors were identified through a multivariable Cox proportional hazards regression model. Of the 645 patients with UTUC included in the present study, 163 (25%) had multifocal UTUC. Kaplan‑Meier analysis indicated that multifocal UTUC synchronous with a high‑level SIRI was significantly associated with poorer outcomes after RNU. Furthermore, the results of the multivariate Cox proportional hazards model analysis demonstrated that multifocal tumor coupled with a high‑level SIRI was an independent factor for predicting a shorter survival and disease progression. In conclusion, the results of the present study indicated that an elevated SIRI significantly influenced the survival rate of patients with multifocal UTUC. Specifically, integrating multifocal UTUC with a high‑level SIRI emerged as an independent risk factor for poorer OS, CSS and RFS. These findings highlighted the potential role of SIRI in the risk stratification and management of patients with multifocal UTUC.

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