T1 Substaging of Nonmuscle Invasive Bladder Cancer is Associated with bacillus Calmette-Guérin Failure and Improves Patient Stratification at Diagnosis

Abstract

Purpose: Currently, markers are lacking that can identify patients with high risk nonmuscle invasive bladder cancer who will fail bacillus Calmette-Gu erin treatment. Therefore, we evaluated the prognostic value of T1 substaging in patients with primary high risk nonmuscle invasive bladder cancer. Materials and Methods: Patients with primary high risk nonmuscle invasive bladder cancer who received !5 bacillus Calmette-Gu erin induction instillations were included. All tumors were centrally reviewed, which included T1 substaging (microinvasion vs extensive invasion of the lamina propria). T1 patients were stratified into high risk or highest risk subgroups according to major urology guidelines. Primary end point was bacillus Calmette-Gu erin failure, defined as development of a high grade recurrence. Secondary end points were high grade recurrence-free survival, defined as time from primary diagnosis to biopsyproven high grade recurrence and progression-free survival. Time-to-event analyses were used to predict survival. Results: A total of 264 patients with high risk nonmuscle invasive bladder cancer had tumor invasion of the lamina propria, of which 73% were classified as extensive invasion and 27% as microinvasion. Median followup was 68 months (IQR 43e98) and bacillus Calmette-Gu erin failure was more common among patients with extensive vs microinvasive tumors (41% vs 21%, p[0.002). The 3-year high grade recurrence-free survival (defined as bacillus Calmette-Guerin failure) for patients with extensive vs microinvasive tumors was 64% vs 83% (p[0.004). In multivariate analysis, T1 substaging was an independent predictor of high grade recurrence-free survival (HR 3.2, p[0.005) and progression-free survival (HR 3.0, p[0.009). Patients with highest risk/microinvasive disease have an improved progression-free survival as compared to highest risk/T1e disease (p.adj[0.038). Conclusions: T1 substaging provides important prognostic information on patients with primary high risk nonmuscle invasive bladder cancer treated with

T1 Bladder Cancer: Comparison of the Prognostic Impact of Two Substaging Systems on Disease Recurrence and Progression and Suggestion of a Novel Nomogram

“…Finally, in our study, the BCG showed a significant impact on prolonging PFS only for T1 a patients. This outcome is in line with the retrospective study of de Jong FC ( 27 ); the authors identified 264 patients with high-grade pT1 tumors and subdivided them as having extensive lamina propria invasion (73%) or microinvasion (27%) according to the substaging T1 m− e . With a median follow-up of 68 months, patients with T1 e had a statistically significant difference in BCG failure (41 vs. 51%; P = 0.002).…”

Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin

“…Formalin fixed paraffin-embedded (FFPE) material, including TURBTs, re-TURBTs, tumor recurrences, random biopsies, radical cystectomies (RC), pelvic lymph node dissections (PLND) and distant metastases were reviewed by an expert uropathologist (R.F.H.) in accordance with WHO standards for classification of the urinary system and was previously published [3, 80]. Patients were classified as high risk or as very high risk subgroup according to the EAU guidelines on NMIBC.…”

“…Initial treatment response to BCG is excellent, yet the long-term efficacy is moderate as HR-NMIBC patients have a 50% risk of developing recurrent disease within 5 years [2]. Furthermore, a 20% risk of progression to advanced disease is observed, which is associated with high mortality [1, 3]. Patients with HR-NMIBC where a tumor recurs or progresses have been exposed to unnecessary BCG toxicity, a delay in radical treatment and have reduced survival [4, 5].…”

This Month in Adult Urology

“…The risk of BCR in the FT group is concerning and will require more analysis with larger patient groups. 6 Patients were stratified into groups of T1m (microscopic) and T1e (extensive) invasion of the lamina propria. Of those with T1e 41% failed BCG treatment with a high grade recurrence compared to 21% with T1m.…”