Neoadjuvant PD-L1 Blockade Combined With Anlotinib to Enable Nephron-Sparing Surgery in Patients With High-Complexity Locally Advanced Clear Cell Renal Cell Carcinoma

Patients with anatomically high-complexity locally advanced ccRCC (RENAL score ≥10) often require radical nephrectomy or technically challenging partial nephrectomy, resulting in increased perioperative risks and long-term renal function impairment. Evidence supporting neoadjuvant strategies in this specific high-complexity population remains limited.

This study evaluates a novel neoadjuvant approach combining PD-L1 blockade (TQB2450) with the multi-target tyrosine kinase inhibitor anlotinib. PD-L1 inhibition restores anti-tumor immunity, while antiangiogenic therapy promotes vascular normalization and enhances immune cell infiltration. This dual mechanism may improve tumor shrinkage and facilitate surgical conversion, particularly in central or hilar tumors.

Patients will receive 2-4 cycles of neoadjuvant therapy, followed by imaging assessment and multidisciplinary team (MDT) evaluation. Surgery will be performed within a predefined window after treatment completion.

A key translational component includes longitudinal ctDNA methylation-based MRD monitoring at four time points (baseline, after 2 cycles, pre-surgery, and post-surgery), combined with tumor tissue RNA expression and DNA methylation profiling, as well as radiomics feature extraction. These data will be integrated using machine learning algorithms to construct predictive models for treatment response and nephron-sparing surgery feasibility.