Prospective Validation of the ROL System in Substaging pT1 High-Grade Urothelial Carcinoma: Results from a Mono-Institutional Confirmatory Analysis in BCG Treated Patients

Abstract

Patients with pT1 high-grade (HG) urothelial carcinoma (UC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resection (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. The ROL system was supposed to be validated on a large prospective series of primary urothelial carcinomas from a single institution. From 2016 to 2020, we adopted ROL for all patients with pT1 HG UC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1 HG UC were analyzed. The median age was 74 years, with a predominance of men (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%), and 131 were ROL2 (59%). At a median follow-up of 26.9 months (IQR 13.8–40.6), we registered 81 recurrences and 40 progressions. ROL was a significant predictor of tumor progression in both univariable (HR 3.53; CI 95% 1.56–7.99; p < 0.01) and multivariable (HR 2.88; CI 95% 1.24–6.66; p = 0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed a correlation with both PFS (p = 0.0012) and RFS (p = 0.0167). Our results confirmed the strong predictive value of ROL for progression in a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG UC, and improving risk tables for urological decision-making.

Influence of lamina propria invasion extension on T1 high‐grade non‐muscle‐invasive bladder cancer in patients undergoing BCG or radical cystectomy

“…Our findings are in agreement with previous studies [24,25]. De Jong et al [24] recently reported on a cohort of 264 patients who received at least five out of six instillations of BCG induction course, demonstrating that extensive invasion of the LP (>0.5 mm or >1 focus) was associated with a higher risk of HG recurrence and progression.…”

“…The ‘Rete Oncologica Lombarda’ (ROL) T1 substaging system was validated in a cohort of patients undergoing treatment with at least one induction course of BCG. Patients with a single focus of LP invasion extending >1.0 mm or multiple foci of LP invasion extending >1.0 mm summed together (ROL 2) showed, in adjusted multivariable regression analysis, a more than twofold risk of progression to MIBC (hazard ratio 2.88; P = 0.01) compared to those with LP invasion <1 mm (ROL 1) [25]. T1 substaging remains underutilised and not routinely reported in pathology reports.…”

Clinical and pathological predictors of persistent T1 HG at second resection

“…Notably, the validity of the ROL sub-staging system for oncological outcomes was recently evaluated and the system reliably stratified patients, with ROL 2 having lower PFS and RFS. 29 Further studies will help consolidate the oncological impact of this innovative staging system. A critical issue with T1 sub-staging systems is their feasibility, which is not the same among different systems.…”