Tumor cell invasion in blood vessels but not lymphatic vessels in TURBT predicts poor prognosis in bladder cancer

BACKGROUND: Vessel invasion (VI) in transurethral resection of bladder tumor (TURBT) is associated with lymph node metastases and reduced survival. Separation of blood (BVI) and lymph (LVI) vessel invasion with immunohistochemistry (IHC) in cystectomy (RC) has indicated different prognosis and could guide treatment already at the time of TURBT. The prognostic impact of BVI and LVI at TURBT has not been elucidated. OBJECTIVE: To examine BVI and LVI separately in TURBT using IHC and investigate their value for predicting nodal metastases, extravesical disease, distant metastases and survival after RC. METHODS: We reviewed TURBT specimens from a retrospective, population-based series of 291 patients later treated with RC regarding VI on routine- stained sections (hematoxylin-eosin-saffron; VI-HES). One tumor block per case was stained using D2-40/CD31 antibodies for separate analysis of BVI and LVI. RESULTS: The frequency of LVI and BVI was 31% and 20%, and VI-HES 31%. BVI independently predicted extravesical disease at RC and distant metastases within 12 months. LVI and VI-HES predicted lymph node metastases. BVI showed reduced recurrence-free survival (RFS; hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.0-2.7, P = 0.035) and disease-specific survival (DSS; HR 1.8, CI 1.1-2.9, P = 0.018) in multivariable analysis, whereas LVI was not significantly related to survival. VI-HES showed reduced DSS and marginal significance for reduced RFS. CONCLUSIONS: At TURBT, IHC improves detection of vessel invasion and differentiates BVI from LVI, enhancing risk stratification compared with VI-HES. Presence of BVI in TURBT specimens predicts distant metastases and reduced survival and should be incorporated in clinical decision-making.