Poster Session 3: Oncology – Bladder

Introduction: Although previous studies have suggested that patients who progress to muscle-invasive bladder cancer (secondary MIBC) after previous treatment for non-invasive disease have worse outcomes than those that present de novo (primary MIBC), contemporary studies have been conflicting.Further, most analyses have generally not assessed possible explanatory factors, although there is emerging evidence that secondary MIBC may be more resistant to perioperative chemotherapy.The aim of the current study was to assess whether there were differences in downstaging, and its association with survival outcomes, in patients with primary MIBC as compared to secondary MIBC in a large, retrospective cohort of patients from tertiary care centers.Methods: This retrospective, multicenter study used the Canadian Bladder Cancer information system (CBCis) database, a registry that includes patient, tumor, and treatment data from 14 centers across Canada.The main study outcome was the rate of downstaging at cystectomy, defined as <pT2.Descriptive statistics were used to compare baseline demographic factors.Cox's proportional hazards models and multivariable regression analyses, adjusted for key patient and treatment variables, were performed to assess factors associated with downstaging, as well as overall survival (OS).Results: During the study period, 908 patients received cystectomy between January 5, 2017, and September 1, 2020.Patients had localized primary MIBC (n=678) or secondary MIBC (n=230) at the time of TURBT.There were no observed differences in baseline variables based on MIBC status (primary vs. secondary), including sex, age at surgery, comorbidity, clinical stage, variant pathology, or use of neoadjuvant chemotherapy (NAC, 47% vs. 44%, p=0.43).Postoperatively, there were observed differences in rate of lymph node metastases (primary vs. secondary; 16% vs. 59%, p=0.037) and subsequent use of adjuvant chemotherapy (5 vs. 9%, p=0.016).Downstaging to <pT2 for those with primary MIBC was 28% vs. 14% with secondary MIBC (p<0.001) and downstaging to pT0 was 15% vs. 5%, respectively.Multivariable analysis of factors associated with downstaging at cystectomy included urothelial (vs.variant) pathology (OR 6.39, 95% CI 3.22-12.69),use of NAC (OR 2.23, 95% CI 1.39-3.60),and primary vs. secondary MIBC (OR 2.65, 95% CI 1.50-4.71).Lower OS was also associated with those with secondary vs. primary MIBC (HR 2.90, 95% CI 1.64-5.14,p<0.0001).Conclusions: In this large, multicenter registry of patients with MIBC, those who had secondary, progressed disease were observed to have decreased survival on multivariable analysis.Further, those cases were associated with lower downstaging rates post-cystectomy vs. those with de novo, primary MIBC.Limitations of these observations include selection biases of those registered in CBCis and incomplete details of previous management for non-invasive disease.Although these observations are likely confounded by assessed clinical stage at the time of cystectomy, they support further work investigating the chemosensitivity of MIBC that has progressed from non-invasive disease, as it may represent a more global, treatment-resistant phenotype.