Effect of neoadjuvant chemotherapy on locally advanced upper tract urothelial carcinoma: A systematic review and meta-analysis

Background: The role of neoadjuvant chemotherapy (NAC) for the management of upper tract urothelial carcinoma (UTUC) remains controversial. The aim of present study was to evaluate the contemporary role of NAC for patients with locally advanced UTUC through systematic review and meta-analysis of the literature. Methods: Systematic literature searches were conducted in PubMed/Medline and Embase for all studies that examined the role of chemotherapy for UTUC. We performed this study according to the Preferred Reported Items for Systematic Reviews and Meta-analysis guidelines. Endpoints were overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Results: A total of four trials on 318 patients were included in this study. Each of the included studies was retrospective. Compared to controls, NAC improved OS, CSS, and PFS by 57% (95% confidence interval [CI], 0.25-0.73; p = 0.002), 59% (95% CI, 0.27-0.57; p < 0.00001), and 45% (95% CI, 0.50-0.60; p < 0.00001), respectively. The absolute increases in OS, CSS, and PFS were 11%, 18%, and 13%, respectively, and these increases are equivalent to numbers-needed-to-treat of 9, 5.5, and 7.6, respectively. Pooled odds ratio for the effect of NAC on downstaging was 0.21 (95% CI, 0.09-0.60; p = 0.004), which indicates that NAC group had a 4.76-fold higher probability of having pathologic N stage 0 than control group. Conclusions: NAC treatment before radical nephroureterectomy might provide better survival outcomes in patients with locally advanced UTUC. Prospective randomized studies are needed to confirm the benefits of NAC in locally advanced UTUC patients.