Differential Prognosis and Response of Denovo vs. Secondary Muscle-Invasive Bladder Cancer: An Updated Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Bladder cancer is one of the leading causes of death worldwide. About 75% of patients initially present with non-muscle-invasive disease, while the rest presents with primary muscle-invasive disease. Up to a third of non-muscle-invasive bladder cancers progresses into secondary muscle-invasive bladder cancer. Little is known about clinical outcomes after upfront neoadjuvant cisplatin-based chemotherapy and subsequent radical cystectomy for secondary muscle-invasive bladder cancer compared to primary muscle-invasive bladder cancer. Here, we systematically reviewed the current literature evaluate oncological outcomes between primary and secondary muscle-invasive bladder cancer. ABSTRACT: To evaluate oncological outcomes of primary versus secondary muscle-invasive bladder cancer treated with radical cystectomy. Medline, Embase, Scopus and Cochrane Library were searched for eligible studies. Hazard ratios for overall survival (OS), cancer specific survival (CSS) and progression free survival (PFS) were calculated using survival data extracted from Kaplan-Meier curves. A total of 16 studies with 5270 patients were included. Pooled analysis showed similar 5-year and 10-year OS (HR 1, p = 0.96 and HR 1, p = 0.14) and CSS (HR 1.02, p = 0.85 and HR 0.99, p = 0.93) between primMIBC and secMIBC. Subgroup analyses according to starting point of follow-up and second-look transurethral resection revealed similar results. Subgroup analyses of studies in which neoadjuvant chemotherapy was administered demonstrated significantly worse 5-year CSS (HR 1.5, p = 0.04) but not 10-year CSS (HR 1.36, p = 0.13) in patients with secMIBC. Patients with secMIBC had significantly worse PFS at 5-year (HR 1.41, p = 0.002) but not at 10-year follow-up (HR 1.25, p = 0.34). This review found comparable oncologic outcomes between primMIBC and secMIBC patients treated with RC regarding OS and CSS. Subgroup analysis showed worse 5-year CSS but not 10-year CSS for neoadjuvant chemotherapy in the secMIBC group. Prospective clinical trials incorporating molecular markers, that allow precise risk stratification of secMIBC and further research uncovering underlying molecular and clinical drivers of the heterogeneous group of secMIBC is needed.