Direct head-to-head comparison between neoadjuvant and adjuvant chemotherapy in upper tract urothelial carcinoma: A systematic review and meta-analysis

The optimal timing of perioperative chemotherapy in upper tract urothelial carcinoma (UTUC) remains debated. We conducted a meta-analysis to compare neoadjuvant chemotherapy (NAC) versus adjuvant chemotherapy (AC) in terms of pathological and survival outcomes. A systematic search identified eligible studies directly comparing NAC and AC in UTUC patients. Five studies with 1938 patients were included. Compared with AC, NAC achieved higher rates of pathological downstaging (OR: 2.13; 95% CI: 1.21–3.76) and a lower risk of positive surgical margins (OR: 0.59; 95% CI: 0.37–0.95). In contrast, lymph node metastasis rates and overall survival were similar between the two groups. Importantly, although renal function outcomes were not directly reported, prior evidence highlights the risk of post-nephrectomy renal decline, which may limit cisplatin eligibility—underscoring the rationale for NAC. Overall, NAC provides superior pathological benefits while maintaining comparable survival outcomes, supporting its consideration in eligible patients. Given the risk of post-surgical renal function decline, NAC should be considered in eligible patients to ensure timely delivery of cisplatin-based regimens. Future studies should incorporate renal functional outcomes to guide treatment selection.