Introduction

Management of T1 bladder cancer (BC) is controversial and reliable prognostics are urgently needed. We evaluated the clinical impact of two systems to sub-stage T1-BC on a large series of T1-BC patients treated with Bacillus Calmette-Guerin (BCG).

Methods

We included 601 patients with primary (first tumor) T1-BC, who were treated with at least one induction schedule of BCG instillations and followed in four university hospitals. The slides were reviewed by 3 uro-pathologists and sub-staged according to two classifications: Metric sub-stage according to T1micro-invasive (T1m - lamina propria invasion <0.5mm) vs. T1extensive-invasive (T1e - invasion ≥0.5mm) and secondly, according to presence or absence of muscularis mucosae invasion (MM - T1a vs. T1b). Prognostic value for progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed for each system with a multivariable step-wise cox-regression model. We corrected for sex, age, size (>3cm vs. ≤3 cm), concomitant CIS, WHO 1973 and WHO 2004 grade.

Results

Median follow-up was 5.9 (IQR 3.3-9.0) years. Median age was 71 (IQR 15) years, 150 (25%) patients were female. Concomitant CIS was found in 196 (33%) cases. Metric sub-staging was possible in all cases. T1m was found in 213 (35%) tumors vs. 388 (65%) T1e. Based on MM invasion, 281 (47%) tumours were staged T1a vs. 320 (53%) T1b. MM was identified at the invasion front in 466 (78%) tumors. During follow-up, progression (≥cT2 and/or N1 and/or M1) was found in 148 (25%) patients and 95 (16%) patients died of BC. On univariable analysis, both sub-staging systems were significantly associated with PFS and CSS. On multivariable analysis, metric (T1m/e) sub-stage (T1e vs. T1m; HR 3.8, 95%CI 2.3-6.0, p<0.001) and WHO 1973 grade (G3 vs. G2; HR 1.8, 95%CI 1.2-2.7, p=0.006) were prognostic for progression. Independently associated with worse CSS were T1e (HR 2.7, 95%CI 1.6-4.8), WHO 1973 G3 (HR 2.6, 95%CI 1.4-4.7, p=0.002), increasing age (HR 1.03, 95%CI 1.01-1.05, p=0.002) and tumor size >3 cm (HR 1.8, 95%CI 1.2-2.9, p=0.008). _x000D_

Conclusions

In this multi-center study, metric (T1m/e) sub-stage proved a very reliable and strong prognosticator for progression and cancer-specific survival. Our results suggest that metric T1 sub-stage may aid in treatment decision-making between conservative treatment and radical cystectomy for clinical T1-BC. T1a/b sub-stage has inferior prognostic value and reproducibility. Ultimately, metric sub-stage (T1m/e) may be incorporated in the TNM classification system for urinary BC.

Funding

None