Neoadjuvant Radiation Before IVC Thrombectomy Meets RFS Goal in RCC

Stereotactic ablative radiotherapy (SABR) delivered to inferior vena cava tumor thrombus (IVC-TT) before surgery was feasible and showed a preliminary recurrence-free survival (RFS) signal in patients with renal cell carcinoma (RCC), according to results of a trial published in JAMA Oncology.¹

In the phase 2 nonrandomized single-center study (NCT02473536), conducted at UT Southwestern Medical Center, the 1-year RFS rate was 71.4% (80% CI, 56.6%-82.0%; 95% CI, 47.2%-86.0%) among 21 evaluable patients, compared with a prespecified historical benchmark of 55.7% for surgery alone (P = .09). The result satisfied the trial’s phase 2 screening criterion, which used a 2-sided α of 0.20. Investigators emphasized that, given the nonrandomized design and permissive α, the finding is hypothesis-generating rather than confirmatory.

No patient died within 90 days of surgery, and no grade 4 or 5 toxic effects were attributed to radiation. Median follow-up was 108.6 months (range, 2.0-127.2).

“This approach provides a potential pathway to meaningfully improve the outcome for patients with kidney cancer and [IVC-TT],” said Raquibul Hannan, MD, PhD, professor of radiation oncology, immunology, and urology and chief of the Genitourinary Radiation Oncology Service at UT Southwestern Medical Center in Dallas, Texas, in a news release.²

Background of IVC-TT

An estimated 4% to 10% of patients with RCC develop IVC-TT, a serious complication that can interfere with blood flow and extend further to the heart.² According to the NCCN guidelines, the preferred treatment is radical nephrectomy, and the assistance of cardiovascular surgeons may be required because treatment-related mortality may reach 10% depending on the extent of the tumor and level of vena caval extension.³ Recurrence can be frequent despite nephrectomy and thrombectomy.

Study Design

Eligible patients were adults who had newly diagnosed RCC with Mayo level II or higher IVC-TT and who were judged suitable for both SABR and definitive surgery after multidisciplinary review. They were to receive radiation targeted at the radiographically defined tumor thrombus, using contrast-enhanced MRI when feasible to separate it from bland thrombus, at a dose of either 40 Gy in 5 fractions or 36 Gy in 3 fractions. Radical nephrectomy with IVC thrombectomy followed 4 to 14 days later. Adjuvant systemic therapy was not allowed before metastatic recurrence.¹

The primary end point was 1-year RFS. Secondary end points included 90-day perioperative morbidity and mortality, adverse events, pulmonary embolism, overall survival (OS), and cancer-specific survival (CSS). Ki-67 immunohistochemistry and tumor-informed circulating tumor DNA (ctDNA) were exploratory end points. The completed trial builds on previously published results from its safety lead-in, which allowed enrollment of patients with metastatic disease.⁴

From July 2015 to January 2024, all 23 patients completed SABR; 22 proceeded to surgery.¹ Two patients were left out of the primary analysis: 1 whose disease was considered unresectable, and 1 who had no documented recurrence before dying of COVID-19 pneumonia 136 days after resection. In the efficacy cohort, the median age was 62.5 years (IQR, 54.0-73.2), 57% of patients were male, 19 had clear-cell histology, every tumor was high grade (grade 3 or 4), and 3 patients had metastatic disease at study entry.

Survival Outcomes

One-year OS and CSS were each 95.2% (95% CI, 70.7%-99.3%). Median RFS was 13.7 months (80% CI, 12.3-37.8), median OS was 49.8 months (95% CI, 23.7-not reached), and median CSS was 80.9 months (95% CI, 37.8-not reached).

In the 18 patients without metastatic disease, 1-year RFS was 66.7% (80% CI, 50.3%-78.7%; 95% CI, 40.3%-83.4%). Although that estimate sat above the benchmark, the authors noted that its lower 80% confidence bound fell below 55.7%.

Most recurrences and progression events occurred at distant sites, frequently the lungs. Only 1 local recurrence was observed, although the investigators cautioned that this cannot be attributed to SABR in the absence of a surgery-alone control.

Safety Findings

Across the 23-patient safety cohort, 25 grade 3 and 4 grade 4 treatment-attributed adverse events occurred. There were 4 grade 3 events attributed to SABR, with none of grade 4 or 5; surgery accounted for 23 grade 3 and 4 grade 4 events. There were no cases of pulmonary embolism or acute thrombus-related complications.

In the efficacy cohort, 3 patients (14%) had Clavien-Dindo grade III to V complications, and 3 (14%) required cardiopulmonary bypass or thoracotomy. Median operative time was 217 minutes, and median hospital stay was 5 days.

Exploratory Biomarker and Abscopal Observations

Irradiated thrombi showed lower proliferative activity than 5 nonirradiated control pairs, with a mean change in Ki-67 index of −2.18% vs 3.90% (P = .04). Tumor-informed ctDNA was detected in all 16 patients with plasma samples. Among 7 patients with paired samples, tumor fraction fell in 6, and a molecular rise after the nadir was seen only in patients who later had recurrence or progression.

Of the 3 patients with metastatic disease at enrollment, 2 had regression of nonirradiated metastases after SABR without systemic therapy, which Hannan characterized as a possible abscopal effect in the news release. The authors characterized these cases as anecdotal, cautioning that they do not establish a systemic immune effect because metastatic RCC can regress spontaneously.

“Blood continually brings immune cells into a tumor growing inside a vein. By damaging that tumor, radiation may help teach the immune system to recognize cancer elsewhere, the so-called abscopal effect,” Hannan stated. “That possibility is exciting and deserves further study.”

Clinical Implications and Limitations

No neoadjuvant local therapy is established for this population, and the benefit of adjuvant pembrolizumab (Keytruda), which has improved outcomes in high-risk RCC, remains incompletely defined for patients with IVC tumor thrombus, according to the authors. They recommended further study of neoadjuvant SABR, particularly in combination with contemporary immunotherapy. They also raised the hypothesis that SABR alone could control viable thrombus, allowing laparoscopic nephrectomy alone in place of complex open thrombectomy. UT Southwestern investigators proposed launching a national randomized study of that strategy.

Limitations included the single-arm, single-center design, small sample, comparison with a nonmatched historical cohort that included only level III to IV thrombi, a 9-year enrollment period, and the use of 2 fractionation schedules.

“Combining radiation and surgery gives us a new way to approach one of the most challenging complications of kidney cancer,” said Vitaly Margulis, MD, professor of urology at UT Southwestern Medical Center, in the news release.

REFERENCS

1. Hannan R, Lin L, Assadi R, et al. Neoadjuvant stereotactic ablative radiotherapy before inferior vena cava thrombectomy for renal cell carcinoma: a phase 2 nonrandomized clinical trial. JAMA Oncol. Published online October 15, 2026. doi:10.1001/jamaoncol.2026.4172

2. Targeted radiation shows promise for life-threatening kidney cancer complication. News release. UT Southwestern Medical Center. October 15, 2026. Accessed October 19, 2026. https://tinyurl.com/5afrh2sw

3. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 2.2027. Accessed October 19, 2026. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf

4. 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. 2021;110(4):1135-1142. doi:10.1016/j.ijrobp.2021.01.054