Elevated Preexisting Lymphocytic Infiltration in Tumor Stroma Predicts Poor Prognosis in Resectable Urothelial Carcinoma of the Bladder

Abstract

Aims

Lymphocytic infiltration is predominantly distributed in the tumor stroma and represents the tumor‐related immune response. This study was to elucidate the prognostic value of stromal lymphocytic infiltration (SLI) in resectable urothelial carcinoma of the bladder (UCB).

Methods

The prognostic significance of SLI in UCB was assessed in a discovery (n=226; 60 deaths) cohort and a validation cohort (n=417; 103 deaths). SLI was categorized into intense (≥50% SLI) and non‐intense (<50% SLI). Multivariable Cox model was used to analyze the association of SLI score with overall survival (OS) and disease‐free survival (DFS). Immunofluorescence staining was used to examine the composition and phenotypes of SLI.

Results

Median follow‐up time was 58.1 and 64.9 months in the discovery and validation cohorts, respectively. SLI were intense in 38.1% of patients in the discovery cohort compared with 20.9% in the validation cohort (P<0.001). SLI score had independent prognostic value on OS (HR, 2.132; P=0.016) and DSS (HR, 1.952; P=0.04) in the discovery cohort, which was confirmed in the validation cohort (OS: HR, 1.636; P=0.023; DSS: HR, 1.627; P=0.029). SLI score was positively associated with histological grade, tumor stage, and lymph node status in both cohorts. Moreover, in the stroma, not only infiltrated with inhibitory immune cells, but also expressing several major immune checkpoint molecules PD‐1, PD‐L1, IDO and TIM‐3.

Conclusion

Intense preexisting SLI was validated as a reliable poorer prognostic marker for survival in UCB, which may add to the prognostic significance of the AJCC/UICC TNM classification.

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