Treatment with stereotactic ablative radiotherapy yielded non-inferior long-term survival compared with video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection in operable stage IA non–small cell lung cancer.
Long-term survival following treatment with stereotactic ablative radiotherapy (SABR) appeared to be non-inferior to video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND) in patients with operable stage IA non–small cell lung cancer (NSCLC), according to findings from the revised STARS trial (NCT02357992).
No significant differences between overall survival (OS) were noted between the 2 cohorts of patients (HR, 0.86; 95% CI, 0.45-1.65; P = .65). Findings from the trial indicated that the median OS had not yet been reached in the SABR group (95% CI, not reached [NR]–NR), and the OS rate at 3 years and 5 years was 91% (95% CI, 85%-98%) and 87% (95% CI, 79%-95%), respectively. In the VATS L-MLND cohort, the 3-year OS rate was 91% (95% CI, 85%-98%) and the 5-year rate was 84% (95% CI, 76%-93%). The study had a median follow up of 5.1 years.
“These results are important because the pooled analysis of the STARS and ROSEL trials had notable limitations; as a result, the SABR group of the STARS trial was re-accrued with greater sample size, and long-term follow-up was achieved and compared per protocol with that of a contemporary institutional cohort of VATS L-MLND cases,” the investigators wrote. “This study, however, is not a substitute for phase 3 trials (eg, VALOR [NCT02984761], which could take at least another 5 years for enrollment, along with additional time for follow-up).”
The single arm, prospective STARS trial enrolled new patients who had similar primary and secondary objectives, eligibility, and SABR dosing. The study enrolled patients who were 18 years or older with newly diagnosed, histologically confirmed NSCLC. A Zubrod performance status of 0 to 2 was required, as well as a tumor diameter of 3 cm or less. Those with carcinoid histology, synchronous primary lung cancer, and prior lung or mediastinal radiotherapy were not eligible to enroll.
Radiation was given at a dose of 54 Gy in 3 fractions or 50 Gy in 4 fractions with a simultaneous integrated boost to the internal gross tumor volume of 60 Gy. SABR was administered on consecutive days. Those who received VATS L-MLND did so by high volume thoracic surgeons specializing in thoracic cancer surgery.
The study's primary end point was OS at 3 years, with secondary end points including progression-free survival (PFS) and cancer-specific survival (CSS).
Eighty patients were enrolled from September 1, 2015, to January 31, 2017, with the final follow-up date being September 30, 2020. Most patients who enrolled had adenocarcinomas and 67% had tumors that were peripherally situated. The mean tumor size was 1.83 cm.
Additional findings from the SABR cohort indicated that 10 patients had died as of the data lock on September 30, 2020, 6 of which were cancer specific. Moreover, 15 patients developed disease progression. The median PFS was not reached (95% CI, NR-NR, and the 3-year and 5-year PFS rates were 80% (95% CI, 72%-89%) and 77% (95% CI, 68%-87%). A similar PFS was identified in the VATS-L-MLND cohort, with a rate of 88% at 3 years (95% CI, 81%-96%) and 80% at 5 years (95% CI, 71%-90%; P = .57). Moreover, the median CSS had not been reached, and the 3-year and 5-year CSS rates were 95% (95% CI, 90%-100%) and 92% (95% CI, 86%-98%).
In terms of safety, investigators reported that SABR was well tolerated and produced no grade 4/5 toxicities. Adverse effects (AEs) included grade 3 dyspnea (1%), grade 2 pneumonitis (1%), and grade 2 lung fibrosis (1%). Notably, no serious AEs, treatment modifications, or treatment interruptions occurred after treatment with SABR.
The most common AEs that occurred in the VATSL-MLND cohort were pulmonary (38%) and cardiovascular (13%). Other complications included renal failure (1%), gastrointestinal complications (4%), genitourinary complications (4%), postoperative transfusion (5%), bleeding requiring readmission (1%), and wound complications (5%).
Chang JY, Mehran RJ, Feng L, et al. Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery. Lancet Oncol. 2021;22:1448-1457. doi:10.1016/S1470-2045(21)00401-0