Neoadjuvant SABR before nephrectomy improved 12-month RFS vs surgery alone in patients with RCC with IVC tumor thrombus, with manageable safety.
Neoadjuvant stereotactic ablative radiation therapy (Neo-SABR) before surgery led to a relapse-free survival (RFS) at 12 months that exceeded historical benchmarks with surgery alone in the treatment of inferior vena cava tumor thrombus (IVC-TT) in patients with renal cell carcinoma (RCC), according to data from a phase 2 study (NCT02473536) presented at the
At a median follow-up of 35.2 months, patients who received Neo-SABR before surgery (n = 21) at 40 Gy/fx or 36 Gy/3 fx experienced a 12-month RFS rate of 71.4% (80% CI, 0.56%-82.0%; P = .087) compared with 55.7% with surgery alone. These data met the prespecified primary efficacy end point of this trial, translating to a 16.7% increase in RFS at this time point.
“We found a sweet spot because within 2 weeks of radiation, not that many changes can be observed in terms of tissue and thrombus. [Therefore,] we do not anticipate too much of a surgical approach change in this respect. I think the window of performing the surgery [in this trial] was the key aspect of it,” said lead study author Lin Lin, MD, in an interview with OncLive®. Lin is a urologic oncology fellow in the Division of Urology at UT Southwestern, in Dallas, Texas.
It is known that up to 10% of patients with RCC will develop IVC-TT, and standard treatment comprises radical nephrectomy with IVC thrombectomy with or without adjuvant treatment. The perioperative mortality from the approach is 10.8%, and 5-year cancer-specific survival (CSS) rates range from 25% to 53%. With the current study, investigators sought to examine the efficacy and long-term outcomes of Neo-SABR for IVC-TT.
The prospective, open-label, single-center, safety lead-in, single-arm study enrolled patients who had newly diagnosed RCC with Mayo level II to IV IVC-TT and were at least 18 years of age and had an ECOG performance status from 0 to 2.1,2 Patients must be eligible to receive SABR, nephrectomy, and thrombectomy. If patients previously received radiotherapy to a target within 3 cm of their IVC-TT, had a history of pulmonary hypertension or embolism, or had brain metastases that were not treated, they were excluded.
Participants were administered Neo-SABR to only their IVC-TT at doses of 40 Gy/fx or 36 Gy/3 fx for 4 to 14 days before undergoing radical nephrectomy and IVC thrombectomy. They then entered into follow-up. The trial’s primary end point was 12-month RFS, and key secondary end points included perioperative morbidity; safety in the form of adverse effects (AEs); RFS, overall survival, and ad hoc analysis of CSS; and pulmonary and systemic metastasis.
Baseline characteristics showed that patients had a median age of 62.5 years (range, 54.0-73.2); slightly more than half were male (54.5%) and received a dose regimen of 40 Gy/5 fx (54.5%). Thrombus levels for patients in the study were mostly level II (54.5%); 36.4% had level III, and 9.1% had level IV. Most patients had clear cell histology (90.9%), and only 1 patient each had mucinous tubular and spindle cell or papillary histology. Most patients had a pathologic stage of pT3b (68.2%); the most common N stage was pN0 (54.5%), and the most common M stage was pMx/cM0 (86.4%).
Of the total 23 patients enrolled in the trial between July 2015 and January 2024, 23 received neo-SABR. After 1 patient was excluded due to widespread metastatic disease to the liver, 22 patients underwent surgery. One additional patient was excluded because of perioperative death from COVID-19–related pneumonia, leaving 21 patients to enter the follow-up period.
Data showed that 22.7% of patients experienced thrombi downstaging and 13.6% had cardiopulmonary bypass and thoracotomy. Case duration was 217.5 minutes (range, 115-478, EBL was 800 mL (range, 100-10,000 cc), and 63.6% had intraoperative transfusion. The perioperative mortality rate was 0%. Moreover, 13.6% of patients experienced Clavien-Dindo grade III to IV surgical complications. Patients had a median hospital stay of 4 days (range, 2-63).
No patients in the current study experienced pulmonary embolism, vs not reached (NR) with regard to historical data. Pulmonary metastasis was reported in 57.1% of those in the current study, and 71.4% had systemic metastasis. Just under half (42.9%) of patients received subsequent systemic therapy. The OS and CSS rates at 1 year were both 95.2%; these rates were 65.5% and 66.6% per historical data.
No radiation-related AEs that were grade 4 or higher were reported, although 36.4% of patients experienced perioperative AEs that were grade 3 or higher.
“These results demonstrate promising oncologic efficacy with limited toxicity and support further evaluation of Neo-SABR in this high-risk RCC population,” the study authors concluded.
