Role of Neoadjuvant Chemotherapy on Pathological, Functional, and Survival Outcomes of Upper Tract Urothelial Carcinoma Patients: A Systematic Review and Meta-Analysis.

The role of neoadjuvant chemotherapy (NAC) in upper tract urothelial cancer (UTUC) is not yet confirmed. Therefore, we conducted this review to pool the available evidence in this regard. We analyzed 14117 UTUC patients reported in 21 studies after searching 5 databases. The NAC was administered in 1983 patients and the remaining 12134 controls underwent radical nephroureterectomy (RNU) alone. Efficacy endpoints included pathological, functional, and survival outcomes. Safety was determined by overall and grade 3-4 complications. For dichotomous outcomes, the log odds ratio (logOR) was pooled, and for continuous variables, the crude mean difference was calculated along with its 95% CI. The NAC was associated with 10% complete pathological response (CPR), 42% pathological downstaging, 31% post-NAC advanced disease (pT3-4), 6% positive surgical margin, 18% lymph node metastasis (pN+), 24% lymphovascular invasion, and 29% mortality and recurrence at 5 years. Compared to controls, NAC resulted in increased risk of CPR [logOR=1.67; 95% CI, 0.11-3.23] and downstaging [logOR=1.30; 95% CI, 0.41-2.18] and reduced risk of advanced disease [logOR=-0.81; 95% CI, -1.51--0.11]. Renal function did not improve from baseline; however, it increased significantly after RNU. The NAC was associated with good survival/low mortality in the short term, with a sustained increase over time. Overall and grade 3-4 complications occurred in 25% and 7% of patients, respectively. Our findings support the potential benefits of NAC in enhancing pathological outcomes and possibly improving survival in UTUC patients undergoing RNU. The variability in response and associated complications underscore the importance of careful patient selection and tailored treatment approaches.