Tumor thrombus in the inferior vena cava (IVC) resulting from renal cell carcinoma (RCC) can be safely and effectively treated with stereotactic ablative radiation therapy (SABR) prior to surgery, according to findings from a phase II trial presented at the 26th Annual Meeting of the Society of Urologic Oncology (SUO).1
“Neoadjuvant [SABR] followed by surgery is a feasible and safe approach for [patients with] RCC with IVC thrombus,” said presenting author Lin Lin, MD, PhD, of the Division of Urology at UT Southwestern Medical Center in Dallas.
Background
Up to 10% of patients with RCC develop IVC tumor thrombus, which has 5-year cancer-specific survival rates of between 25% and 53%.2 The standard treatment for patients with RCC and IVC tumor thrombus is IVC thrombectomy with or without adjuvant therapy.
A safety lead-in analysis to the phase II trial explored neoadjuvant SABR of IVC tumor thrombus, which demonstrated safety and feasibility in six patients.3
Study Design
Researchers conducted a prospective, single-center, safety lead-in single-arm phase II trial to explore the efficacy and long-term outcomes of neoadjuvant SABR in patients with newly diagnosed RCC and IVC tumor thrombus.
The overall study included 23 patients with newly diagnosed RCC who had level II to IV IVC tumor thrombus (ie, thrombus extending > 2 cm into the IVC, ranging from below the hepatic veins to above the diaphragm or into the right atrium) and were eligible for SABR, nephrectomy, and thrombectomy. Exclusion criteria included prior radiation therapy within 3 cm of the IVC tumor thrombus, untreated brain metastases, and a prior history of pulmonary embolism or hypertension.
Patients received neoadjuvant SABR to the IVC tumor thrombus only at 40 Gy in five fractions, or 36 Gy in three fractions. Following neoadjuvant radiation therapy at 4 to 14 days, patients underwent radical nephrectomy and IVC thrombectomy. The primary endpoint was relapse-free survival rate at 1 year; secondary endpoints included perioperative morbidity, adverse events, relapse-free survival, overall survival, ad-hoc analysis of cancer-specific survival, and pulmonary and systemic metastases.
Two patients were excluded from the efficacy analysis: one patient in whom surgery was aborted due to widespread metastatic disease in the liver, and the second due to perioperative death from COVID-19–related pneumonia.
Results
More than half of the patients (54.5%) received 40 Gy radiation in five fractions.
Five patients were downstaged intraoperatively for their thrombus level. Three patients received cardiopulmonary bypass and thoracotomy and 14 patients required intraoperative transfusion. The perioperative mortality rate was 0%, compared to a historical rate of 10.8%.
Three patients had severe surgical complications (Clavien-Dindo grade III to IV, indicating the need for surgical, endoscopic, or radiological intervention and/or the occurrence of a life-threatening complication). The average hospital stay was 4 days.
Patients were followed for a median of 35.2 months. At 12 months, the relapse-free survival rate was 71.4% (80% confidence interval [CI] = 56.6%–82.0%; P = .087); historically, the 1-year relapse-free survival rate with surgery alone was 55.7%.
The median relapse-free survival was 13.7 months (80% CI = 12.3–37.8 months). At 1 year, the cancer-specific survival rate and overall survival rate were both 95.2%; comparatively, the 1-year historical rates were about 66%. Subsequent systemic therapy was needed in 42.9% of patients.
Pulmonary metastasis was reported in 57.1% of patients and systemic metastasis in 71.4%.
No radiation-related grade ≥ 4 adverse events were reported, and 36.4% of patients had a perioperative grade ≥ 3 adverse event.
The researchers also conducted Ki-67 staining of the primary tumor and IVC tumor thrombus and found that neoadjuvant SABR reduced Ki-67 expression in the study population (P = .038).
“These results demonstrate promising oncologic efficacy with limited toxicity and support further evaluation of neoadjuvant SABR in this high-risk RCC patient population,” Dr. Lin concluded.
Disclosures: Dr. Lin reported no conflicts of interest. For full disclosures of all study authors, visit SUO.
References
1. Lin L, et al: Phase II trial of neo-adjuvant SAbR for IVC tumor thrombus in newly diagnosed RCC. 2025 SUO Annual Meeting. Presented December 4, 2025.
2. Haddad AQ, Leibovich BC, Abel EJ, et al: Preoperative multivariable prognostic models for prediction of survival and major complications following surgical resection of renal cell carcinoma with suprahepatic caval tumor thrombus. Urol Oncol 33:388.e1-9, 2015.
3. Margulis V, Freifeld Y, Pop LM, et al: Neoadjuvant SABR for renal cell carcinoma inferior vena cava tumor thrombus-safety lead-in results of a phase 2 trial. Int J Radiat Oncol Biol Phys 110:1135-1142, 2021.
