Neoadjuvant Therapy in Patients with Upper Tract Urothelial Cancer: An Updated Systematic Review and Meta-analysis

The role of neoadjuvant chemotherapy (NAC) in patients with upper tract urothelial carcinoma (UTUC) remains controversial, mainly because of the lack of high-level evidence.

We aim to update the evidence on NAC regarding pathological and oncological outcomes in patients with nonmetastatic UTUC. Moreover, we also aimed to give an overview of neoadjuvant immunotherapy (NAI) in the current clinical scenario.

A systematic review of 41 studies on NAC and NAI (eight prospective studies [PS] or randomized clinical trials [RCTs] and 33 retrospective studies [RS]) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcomes of interest included pathological complete response (pCR), pathological partial response (pPR), pathological downstaging, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Pooled analyses were performed using effect sizes for pathological outcomes and hazard ratios (HRs) for survival outcomes. Finally, 5-yr proportions were summarized when a 5-yr time threshold was available.

Of the 41 articles, 30 (five PS or RCTs and 25 RS) were eligible for meta-analysis (n = 2384 patients). The pooled pCR, pPR, and pathological downstaging rates were, respectively, 11% (95% confidence interval [CI]: 10-12), 44% (95% CI: 38-50), and 20% (95% CI: 10-37). Compared with radical nephroureterectomy (RNU), NAC was associated with pooled HRs of 0.56 (95% CI: 0.39-0.80) for OS, 0.47 (95% CI: 0.26-0.85) for CSS, and 0.55 (95% CI: 0.24-1.26) for DFS. Evidence on NAI remains limited in terms of sample size and is primarily derived from early-phase studies.

NAC was associated with favorable oncological outcomes compared with RNU alone. Nevertheless, the absence of prospective randomized studies limits the strength of the evidence, and further high-quality trials are warranted to confirm these findings.