Prognostic Analysis of Diagnostic Ureteroscopic Biopsy for Intravesical Recurrence of Upper Urinary Tract Urothelial Carcinoma.

OBJECTIVE: The aim of this study was to investigate whether diagnostic ureteroscopy (URS) biopsy is unfavourable for bladder tumour recurrence in upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We performed a retrospective analysis of 195 patients diagnosed with UTUC, who were divided into a diagnostic URS group (URS+) and a nondiagnostic URS group (URS-) according to whether diagnostic ureteroscopic biopsy was performed. A Cox regression model was used to analyse the risk factors for intravesical recurrence (IVR)-free survival (IRFS) and overall survival (OS) in UTUC after radical nephroureterectomy (RNU). Kaplan-Meier analysis was used to estimate the influence of factors on the incidence of IVR and the cumulative survival rate of UTUC. RESULTS: Patients with a maximum tumour diameter of less than 3.1 cm, low-stage tumours, and ureteral tumours were more likely to undergo diagnostic URS before radical surgery. Multivariate Cox regression analysis showed that tumour pathological stage and diagnostic ureteroscopic biopsy can be used as predictors of IVR after RNU (p = 0.019, 0.033). Kaplan-Meier survival analysis found that diagnostic ureteroscopic biopsy was a high-risk factor for IRFS (p = 0.034). Subcomponent analysis showed that pTa/Tis/T1, pT2, pT3/pT4 stage, and diagnostic ureteroscopic biopsy with pTa/Tis/T1 stage were unfavourable for IVR (p = 0.047). CONCLUSION: Diagnostic ureteroscopic biopsy before RNU should be carefully selected for patients with atypical preoperative UTUC. We believe that intravesical chemotherapy drug perfusion can be used after surgery to prevent IVR if biopsy is unavoidable, but this still requires further prospective studies.

The prognostic and clinicopathological significance of Tim-3 and PD-1 expression in the prognosis of upper urinary tract urothelial carcinoma.

OBJECTIVE: Upper urinary tract urothelial carcinoma (UTUC) is a relatively uncommon disease with few reported molecular markers. This study evaluated Tim-3 and PD-1 expression in primary UTUC and its impact on patients' clinical outcomes. METHODS: Tim-3 and PD-1 protein expression was detected by immunohistochemistry in paraffin-embedded sections from 101 UTUC patients. The H-score was correlated with clinicopathologic outcomes and the long-term recurrence and survival rates. RESULTS: T cell immunoglobulin mucin-3 (Tim-3) protein was overexpressed in UTUC cells, especially tumour-infiltrating lymphocytes (TILs) and endothelial cells. We found that 95% (95/101) of UTUC tissues had dysregulated Tim-3 expression, of which 44% (44/101) showed high expression. High Tim-3 expression (H-score≥100) was significantly correlated with advanced pathological grade, advanced T stage and tumour recurrence (P=0.016, 0.001 and < 0.001, respectively) and with poor intravesical recurrence-free survival (IRFS) and overall survival (OS) (P< 0.001 and 0.003). Moreover, another immune checkpoint molecule, programmed death receptor-1 (PD-1), was also assessed in our study. Among patients in the low Tim-3 expression subgroup, those with high PD-1 expression experienced intravesical recurrence (IVR) more often than those with low PD-1 expression (P< 0.001). However, the PD-1 expression level had no effect on prognosis in the high Tim-3 expression subgroup. CONCLUSION: We confirmed that high Tim-3 protein expression can be used as an indicator of earlier IVR and shorter OS in patients with UTUC, while high expression of PD-1 is only related to earlier IVR. We showed that Tim-3 plays a more important role in tumour recurrence and progression than PD-1. Collectively, our findings support the use of Tim-3 and PD-1 as clinical prognostic factors indicating poor patient survival. Tim-3, alone or in combination with PD-1, could become a target for future UTUC therapies, but further prospective studies are needed.