Tumor cell invasion of blood vessels predicts poor survival in upper tract urothelial carcinoma following radical nephroureterectomy

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OBJECTIVES: Lymphovascular invasion (LVI) is an established adverse prognostic factor in urothelial carcinoma; however, prior studies have rarely distinguished lymphatic vessel invasion (LymVI) from blood vessel invasion (BVI). We investigated the prevalence and prognostic significance of LymVI and BVI in upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNUx), and assessed their associations with clinicopathological characteristics and metastatic patterns. METHODS: We retrospectively analyzed 455 patients who underwent RNUx at Jikei University Hospital and six affiliated centers between 2012 and 2021. LVI subtype was assessed using hematoxylin-eosin staining, supplemented by D2-40, CD31, and Elastica van Gieson staining when required. Patients were categorized into four groups: no LVI, LymVI only, BVI only, and combined LymVI+BVI. Outcomes included non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Kaplan-Meier methods and Cox regression analyses were used to evaluate prognostic associations. RESULTS: LVI subtypes were distributed as follows: no LVI (65.1%), LymVI only (9.9%), BVI only (7.7%), and combined LymVI+BVI (17.4%). Higher pathological T and N stages were observed progressively across these groups (P < 0.001). BVI only and combined LymVI+BVI were independent predictors of inferior NUTRFS (HR 4.52 and 5.01), OS (HR 2.46 and 2.73), and CSS (HR 2.85 and 4.06), whereas isolated LymVI did not significantly affect outcomes. Hematogenous metastases to the lung, liver, and bone were significantly more frequent in patients with BVI or combined LVI. CONCLUSIONS: Distinguishing BVI from LymVI provides refined prognostic stratification in UTUC. BVI, alone or combined with LymVI, is strongly associated with adverse survival and increased hematogenous dissemination, while isolated LymVI has limited prognostic impact. Routine pathological subclassification of vascular invasion may improve postoperative risk assessment and guide adjuvant treatment decisions.