Phase 2 trial of neoadjuvant stereotactic ablative radiotherapy before inferior vena cava thrombectomy in renal cell carcinoma

Renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus is associated with substantial perioperative risk and frequent recurrence despite nephrectomy and thrombectomy. No established neoadjuvant local therapy exists for this high-risk population. A nonrandomized phase 2 trial at University of Texas Southwestern Medical Center (Dallas, TX) evaluated the feasibility,safety, clinical outcomes, and exploratory biomarker effects of neoadjuvant stereotactic ablative radiotherapy (SABR) targeting IVC tumor thrombus before nephrectomy and thrombectomy. The trial enrolled patients with newly diagnosed RCC and Mayo stage II to IV IVC tumor thrombus. The primary endpoint was 1-year recurrence-free survival (RFS) rate compared with a prespecified historical surgery-alone benchmark of 55.7%. Among 23 patients who received neoadjuvant SABR, 22 completed surgery and thrombectomy, and 21 were included in the primary RFS analysis. At a median follow-up of 108.6 months (range 2.0-127.2), 1-year RFS rate was 71.4% (95% CI 47.2-86.0) meeting the prespecified criterion; one-year overall survival rate and cancer-specific survival rate both were 95.2%. No 90-day perioperative mortality occurred; four grad 4 treatment-attributed events occurred. The authors conclude that in this nonrandomized clinical trial, neoadjuvant SABR before nephrectomy and IVC thrombectomy was feasible with an acceptable safety profile.