Oncological outcomes and prognostic implications of T1 histo-anatomic substaging in the management of high-Grade non-muscle invasive bladder cancer: results from a large single centre series

Purpose: This study aimed to comprehensively evaluate the prognostic value of T1 histo-anatomic substaging (T1a/T1b) for high grade (HG) non-muscle invasive bladder cancer (NMIBC) over a large single-centre cohort.

Materials and methods: Patients with primary HG T1 NMIBC were identified from our Institutional database, between 2011 and 2022. Data from diagnosis to repeated transurethral resection of bladder tumour (RE-TURBT), bacillus Calmette-Guérin (BCG) treatment and follow-up were collected. Patients were stratified based on histo-anatomic landmark into T1a (invasion above the Muscularis Mucosa-MM) and T1b (into/beyond MM). Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the impact of histo-anatomic substaging on recurrence-free survival (RFS), cancer-specific survival (CSS), and progression-free survival (PFS).

Results: Substaging was feasible in 88% of cases. The median (IQR) follow-up was 40 (17-72) months. T1b patients had larger initial tumours (> 3 cm: 43.2% vs. 26.1%, p < 0.001), while upstaging to muscle-invasive bladder cancer (MIBC) at RE-TURBT was more frequent in T1b than in T1a (5.9% vs. 1.5%, p = 0.02). T1b patients without BCG induction had worse RFS and PFS (all p ≤ 0.02) compared to T1a, while no differences were observed in patients who received complete BCG induction. At Multivariate analysis, completing at least a BCG induction course was associated with better outcomes across all endpoints.

Conclusions: Invasion of the MM in primary T1 NMIBC is associated with a higher risk of upstaging to MIBC. Patients who received full BCG induction had similar outcomes regardless of substaging, whereas T1b patients without BCG induction experienced higher recurrence and progression rates.