Impact of clinical and pathological subtypes of carcinoma in situ (CIS) of the bladder: Lessons learned from long-term follow-up of a series of CIS patients treated with BCG.

ABSTRACT Objective Some attempts have previously been made to stratify patients with CIS for the purpose of risk-adapted clinical management and clinical trial design. In particular, two classification systems have been proposed: clinical classification, comprising primary (P-CIS), concomitant (C-CIS), and secondary (S-CIS) disease, and pathological classification, comprising P-CIS, cTa-CIS, and cT1-CIS. The aim of the present study was to assess the impact of both classifications on BCG response, recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). Patients and Methods We performed a retrospective analysis of 386 patients with bladder CIS, with or without associated cTa/cT1 disease, treated with BCG instillations between 2008 and 2015. Patients were stratified according to the two classification systems. Cox multivariate regression models were used to assess the impact of these subtypes on BCG response, RFS, PFS, OS, and CSS. We also performed a cumulative meta-analysis according to PRISMA guidelines. Results The median follow-up was 70.5 months. According to the clinical classification, 34 (8.8%) patients had P-CIS, 81 (21%) S-CIS, and 271 (70.2%) C-CIS. The pathological classification showed 34 (8.8%) patients to have P-CIS, 190 (49.2%) cTa-CIS, and 162 (42%) cT1-CIS. In the overall cohort, BCG response was reported in 296 (76.7%); 159 (41.2%) had recurrence, 55 (14.2%) had progression, and 67 (17.4%) underwent radical cystectomy. Death from any cause was recorded in 135 (35%) and death from urothelial carcinoma in 38 (9.9%). Cox multivariate regression analysis showed that neither clinical classification nor pathological classification is an independent predictive factor for BCG response, RFS, PFS, OS, or CSS after adjusting for confounders. In the pooled meta-analysis, two studies and the present series were included for evidence synthesis, recruiting a total of 941 patients. We found no statistically significant difference across the groups for both classifications with respect to BCG response, RFS, PFS, and CSS. Conclusions Currently, the supporting evidence for an impact of clinical classification and pathological classification on oncological outcomes of CIS of the bladder is insufficient to justify their use to guide clinical management or follow-up.