Splenomegaly has been linked to poor prognosis in certain cancers, potentially due to myeloid-derived suppressor cell (MDSC) accumulation in the spleen. This study evaluates the correlation between splenic volume (SV) and oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We hypothesized that increased SV and reduced lymphocyte percentage (Lym%) are associated with worse prognosis in non-metastatic UTUC patients.

This single-center, retrospective study analyzed 465 non-metastatic UTUC patients who underwent RNU between 2009 and 2020. SV was measured using the cross-sectional area-summed method and standardized to body surface area. Patients were stratified into high and low SV groups based on a receiver operating characteristic (ROC)-derived cutoff of 79 cm³/m², with cancer-specific death as the primary endpoint. Lym% was obtained from preoperative blood tests, with a ROC-derived cutoff of 21%. Patients were categorized into four subgroups based on SV and Lym%. Kaplan–Meier analysis estimated overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS). Multivariate Cox regression identified independent predictors of OS, CSS, and MFS.

Among 465 patients, 206 (44.3%) had high SV. Kaplan–Meier analysis showed significantly shorter OS and CSS in the high SV group (p < 0.05). Patients with both high SV and low Lym% had the worst OS, CSS, and MFS, followed by those with low SV and low Lym%. Multivariate Cox regression confirmed high SV with low Lym% as an independent predictor of worse OS (HR 2.15, 95% CI: 1.42–3.25), CSS (HR 1.98, 95% CI: 1.24–3.15), and MFS (HR 2.05, 95% CI: 1.35–3.10).

Increased SV and reduced Lym% were independently associated with poor oncologic outcomes in UTUC patients after RNU. These findings provide prognostic insights for identifying high-risk patients who may benefit from closer monitoring or intensified adjuvant therapy. Prospective studies are needed to validate this association and assess clinical implications.