Introduction: The management of T1 high-grade (HG) bladder cancer (BC) patients is still a challenging issue in urological practice. Depth and amount of lamina propria (LP) tumor invasion is a key prognostic variable. Compared to other substaging methods, the Rete Oncologica Lombarda (ROL) system - simply based on a 1-mm threshold- showed a high predictive value for tumor progression after transurethral resections of the bladder (TUR) in recent retrospective studies. Our aim was to validate ROL system on a large monoistitutional prospective series of primary urothelial carcinomas from TUR.
Methods: From 2013 to 2020, we prospectively maintained a database of pT1HG BC patients with available clinicopathologic data. Using ROL system for T1 substaging, we adopted a cut-off of 1 mm (diameter of a high-power field, HPF, objective 20x) to stratify tumors in ROL1 and ROL2, corresponding to invasive focus or multiple foci extending together for <1 HPF and for >1 HPF, respectively. Univariate and multivariate Cox proportional hazard models were employed to identify significant independent predictors of recurrence and progression after TUR. Kaplan-Meier (KM) survival estimates were used to investigate ROL’s predictive role on progression free survival (PFS) and recurrence free survival (RFS).
Results: A total of 229 confirmed T1HG BC entered the prospective study. Mean age was 73 yr and most patients were male (74.7%); 70 tumors were multifocal (30.57%), 33 cases had divergent differentiation (14.4%), associated carcinoma in situ (CIS) and lymphovascular invasion (LVI) occurred in 32 (14%) and 20 (9%) cases, respectively. ROL was feasible in all but one case (99.6%): 94 cases were ROL1 (41%) and 134 ROL2 (59%). All patients completed the BCG induction course and at least 1 or 2 maintenance courses. At a median follow up of 23 months (IQR 12.33-38.5), 59 patients had recurrence (25.76%) and 37 patients had progression (16%). ROL was a significant predictor of progression in univariate Cox regression analysis (OR= 3.58, 95% CI, 1.50-8.56; p=0.004), confirmed by the multivariate analysis (OR= 2.95, 95% CI, 1.11-7.87; p=0.03). In KM estimates for PFS and RFS, ROL showed a significant correlation with progression (p < 0.01), while no significance was reached for recurrence (p>0.05).
Conclusions: Our results confirmed the strong predictive role of ROL for progression on a large prospective series. We foster the application of ROL system for substaging T1HG BC, a simple and feasible method that might identify high risk patients and drive urological decision making.