Abstract
This systematic review and meta-analysis evaluated the role of neoadjuvant systemic therapy in enabling partial nephrectomy (PN) for patients with high-complexity or locally advanced non-metastatic renal cell carcinoma (RCC). Thirteen studies, including 359 patients, were analysed, with most investigating vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors (VEGFR-TKIs), while some assessed immune checkpoint inhibitors (IO) alone or in combination. The pooled results showed that neoadjuvant therapy increased the feasibility of PN, achieving high rates of tumour shrinkage and negative surgical margins. Perioperative outcomes, including blood loss and complications, were comparable to upfront surgery, and severe complications were uncommon. Renal function generally declined following treatment, but nephron-sparing approaches preserved kidney function better than radical surgery. Early survival outcomes, including recurrence-free and overall survival, were favourable across studies. These findings suggest that neoadjuvant therapy may be a safe and effective strategy to expand surgical options in complex renal tumours. However, larger prospective trials are needed to validate these results.