The role of primary tumour site surgery in metastatic UTUC: a systematic review and meta-analysis

Objective: To assess the impact of primary tumour surgery on survival outcomes in patients with metastatic upper urinary tract urothelial carcinoma (mUTUC) by conducting a systematic review and meta-analysis. Methods: A systematic search was conducted using the PubMed/Medline, Embase, Web of Science, and Cochrane Library databases for studies published up to January 2025, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible studies included adult patients (≥18 years) diagnosed with mUTUC (cM+ excluding cN + M0). The intervention assessed was primary tumour surgery, compared to non-surgical management, including chemotherapy, immunotherapy, radiation therapy, or best supportive care. Key outcomes measured were surgical/peri-operative outcomes, progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Results: Ten eligible retrospective studies were identified. Most reported a significant improvement in survival outcomes (PFS, CSS and OS) for patients undergoing primary tumour surgery compared to systemic therapy (STx) alone. Surgery was notably associated with superior OS both for STx plus consolidative surgery (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.55–0.81) and cytoreductive surgery plus STx (HR 0.73, 95% CI 0.68–0.78). The most favourable outcomes were observed in younger patients and those with a single metastatic site. Conclusions: Surgery may improve survival outcomes in mUTUC compared to non-surgical options. However, the current evidence is mainly derived from retrospective studies with potential selection bias. Prospective studies are needed to confirm these findings and establish criteria for selecting patients who could benefit from surgical intervention.