Radiation or Surgery in Early Lung Cancer: Does It Make a Difference? - Medpage Today

Long-term survival was equivalent for patients with early-stage non-small-cell lung cancer (NSCLC) whether treated with stereotactic ablative radiotherapy (SABR) or surgery, according to updated results from a prospective study.

In an analysis of an additional 80 patients with medically operable, stage IA NSCLC treated with SABR, the overall survival (OS) rate was 91% at 3 years and 87% at 5 years, reported Joe Chang, MD, of MD Anderson Cancer Center in Houston, and colleagues in The Lancet Oncology.

In comparison, OS following video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND) in a similar cohort of early-stage NSCLC patients was again 91% at 3 years and 84% at 5 years.

Progression-free survival (PFS) rates at 3 years were also similar between the two groups, at 80% for the SABR-treated patients and 88% for the surgically treated patients. At 5 years, these rates were 77% and 80%, respectively.

"Long-term results of this trial extend the results of the published prospective studies, confirming that both surgery and SABR yield similar long-term survival for patients with operable early-stage NSCLC," Chang and co-authors wrote. "Although not randomized, the long-term results of the revised STARS trial show that SABR was non-inferior to VATS L-MLND in terms of overall survival and progression-free survival for patients with operable stage IA NSCLC."

Writing in an accompanying commentary, Alexander Louie, MD, of Sunnybrook Health Sciences Center and the University of Toronto, and co-authors asked whether in light of these new results, it is time to declare a draw between surgery and SABR for early-stage lung cancer. "Current ongoing randomized controlled trials are designed to declare a winner," the commentators said.

These trials include STABLE-MATES, in which OS will be compared between high-risk operable NSCLC patients treated with SABR and those treated with sublobar resection, and the VALOR trial, which is again comparing OS for patients treated with SABR with those treated with lobectomy.

"Randomized controlled trials comparing surgery with non-surgical treatment for cancer have been notoriously difficult to complete, owing to challenges in both equipoise and preference in patients and providers alike," the commentators explained. "STARS has reinforced the validity of the equipoise necessary for these phase III trials."

"[But] until randomized controlled trials are completed, for younger, fitter patients presenting with stage IA NSCLC, it seems that there are two outstanding treatment options available for long-term survival," Louie and co-authors concluded.

An earlier pooled analysis by Chang and colleagues of patients enrolled in the STARS and ROSEL trials showed that SABR led to significantly higher OS rates compared with L-MLND -- but that analysis had "notable limitations," Chang and colleagues pointed out.

To compensate for that, the investigators re-accrued the SABR group within STARS with a larger sample size and performed a propensity matched comparison with a contemporary cohort of patients who had undergone VATS L-MLND at MD Anderson. The current analysis did not include patients from the original STARS study.

Patients treated with SABR had newly diagnosed NSCLC and a tumor diameter of 3 cm or less. The mean tumor size for this cohort was 1.83 cm, and two-thirds of the tumors were adenocarcinomas.

SABR was given at a dose of 54 Gy in three fractions for peripheral lesions or 50 Gy in four fractions for central tumors with simultaneous integrated boost to gross tumor totaling 60 Gy. "All patients completed SABR within 4 days, [and] all patients tolerated this 1 week of radiotherapy without significant side effects," the team said.

All 352 patients in the surgical database of participants with stage I NSCLC who underwent VATS L-MLND during the period of enrollment were included for propensity score matching with the SABR cohort. The primary endpoint was overall survival at 3 years. Based on multivariable analysis, there was no significant difference in OS between the two cohorts (HR 0.86, 95% CI 0.45-1.65), the researchers said.

At 3 years, the rates of cancer-specific survival were again comparable between the two groups, at 95% for SABR patients and 97% for the surgery group. At 5 years, cancer-specific survival rates were 92% and 93%, respectively.

Five-year local recurrence rates were 6.3% for the SABR group versus 1.3% for the VATS L-MLND group, and rates of distant metastases at 5 years were 8.8% for SABR patients and 4.0% for the surgery group.

On the other hand, SABR patients had a higher risk of regional recurrence, at 12.5% versus 2.7% in the VATS L-MLND patients (P=0.017), although as the authors noted, SABR patients did not have a worse OS despite developing regional recurrence. Notably, there were no grade 4/5 toxicities among SABR-treated patients, and the grade 3 toxicity rate was only 1%.

This is in contrast to VATS L-MLND, which was associated with a postoperative morbidity rate of 19-50%. "The outcomes for patients in the SABR group in this study are among the best results reported in the literature," the researchers wrote.

They cautioned, however, that because the risk of regional recurrence was higher in SABR patients, "we strongly encourage close follow-up after SABR and the use of salvage therapy for isolated local and regional recurrence after SABR."

The authors also cautioned against extrapolating the results to patients with tumors in excess of 3 cm and those with "ultra-central" tumors, since both groups had been excluded from the study.

Disclosures

The STARS trial was sponsored by the University of Texas MD Anderson Cancer Center in collaboration with Varian Medical Systems.

Chang reported financial relationships with Varian Medical Systems, Bristol Myers Squibb, AstraZeneca, Legion Healthcare Partner, and Global Oncology One.

Louie reported a financial relationship with AstraZeneca.