Real-World Evidence on Preoperative Targeted Therapy for Renal Cell Carcinoma With Inferior Vena Cava Tumor Thrombus

Previous evidence, predominantly from case studies and small cohort series, has indicated that targeted therapy can induce downgrading of IVC-TT in RCC. However, the optimal targeted agent for effective IVC-TT downgrading remains elusive. This study aimed to evaluate the efficacy and safety of preoperative targeted therapy in RCC patients with IVC-TT and explore the association between different targeted agents and thrombus downgrading.

A retrospective cohort analysis was conducted on 42 RCC-IVC-TT patients who received preoperative targeted therapy between September 2012 and May 2024. The primary endpoint was IVC-TT downgrading rate; secondary endpoints included thrombus length reduction, objective response rates (ORRs; RECIST v1.1), progression-free survival (PFS), and treatment-related adverse events (TRAEs); Common Terminology Criteria for Adverse Events version 5.0. Associations between baseline clinical/radiological-parameters and IVC-TT downgrading were further analyzed.

The cohort had a median age of 54 years (78.6% male). IVC-TT downgrading was observed in 21.4% of patients (1 case from level IV-II, 4 from level III-II, and 4 from level II-I), while 73.8% experienced a measurable reduction in thrombus length. Based on RECIST v1.1, 11.9% of patients achieved partial response, and the disease control rate was 97.6%. Most TRAEs were grade 1-2, with grade 3 events observed in 21.4% of patients and no grade 4-5 events. Axitinib yielded the highest downgrading rate (55.6%) and was significantly associated with IVC-TT downgrading (P = .013). The median PFS of overall populations was 23.1 months, with no significant difference in PFS between axitinib-treated group and the others (P = .099).

Preoperative targeted therapy is effective and well-tolerated in RCC patients with IVC-TT, with a subset of patients achieving meaningful thrombus downgrading. Axitinib was more frequently associated with thrombus downgrading, suggesting a potential role in facilitating surgical planning in this patient population.