The efficacy of neoadjuvant therapy for upper tract urothelial carcinoma: a systematic review and meta-analysis

BACKGROUND AND OBJECTIVES: Upper urinary tract urothelial carcinoma (UTUC) is aggressive and rare, often treated with radical nephroureterectomy (RNU). Neoadjuvant therapy (NAT) prior to RNU is increasingly explored to improve patient outcomes. This study aimed to update evidence on the efficacy of NAT in UTUC through a systematic review and meta-analysis focusing on survival indicators and pathological response rates. METHODS: A comprehensive literature search across PubMed, Embase, Cochrane, and Web of Science up to October 2024 identified 31 eligible studies. Of these, 26 compared NAT to RNU alone, 4 compared NAT to adjuvant therapy (AT), and 1 included comparisons to both. Outcomes included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and pathological complete response (pCR). RESULTS: A total of 27 studies involving 9,195 UTUC patients showed that NAT + RNU significantly improved OS (HR = 0.46), RFS (HR = 0.56), CSS (HR = 0.45), and PFS (HR = 0.30) compared to RNU alone. The pCR rate in the NAT group was 10% versus 0% in the RNU group. Subgroup analysis showed slightly higher pCR rates in prospective than retrospective studies. Additionally, a meta-analysis of 5 studies (2,475 patients) showed that NAT did not improve OS compared to AT. However, NAT was associated with significantly better RFS, highlighting its potential in reducing recurrence. CONCLUSIONS: This meta-analysis supports NAT as a promising preoperative strategy in UTUC, with potential survival and pathological benefits.