Sub-lobar resection not inferior to lobectomy for peripheral cT1aN0 non-small cell lung cancer ≤ 2 cm
To date, the increased detection of small-sized peripheral non-small cell lung cancer (NSCLC) has renewed interest in sub-lobar resection instead of lobectomy, the traditional standard of care. The large international phase III CALGB 140503 [Alliance] study in patients with peripheral cT1aN0 NSCLC and a tumour that is two centimetre or less found that sub-lobar surgery was non-inferior to lobectomy in this patient population.
Lobar resection has been the surgical standard of care for cT1N0 non-small cell lung cancer (NSCLC) since 1995. Sub-lobar resection (SLR) is reserved for a subset of patients with marginal pulmonary reserve. Recently however, JCOG 0802 investigators reported that in fit patients with cT1aN0 NSCLC ≤ 2 cm segmentectomy was not inferior to lobectomy for the primary endpoint of OS. The phase III CALGB 140503 [Alliance] study is a randomised, international trial comparing lobar and SLR in patients with clinical cT1aN0 NSCLC ≤ 2 cm.
Study design
Between June 2007 and March 2017, 1,080 patients with clinical stage IA NSCLC who met preoperative eligibility criteria were registered for the trial. Intra-operative eligibility required patients to have pathologically confirmed NSCLC and node-negative disease at level 10 and up to 2 mediastinal stations prior to randomisation. In total, 697 patients were intraoperatively randomly assigned to either lobar (N= 357) or sub-lobar (N= 340) resection. Randomisation was stratified by tumour size (<1 cm, 1-1.5 cm, >1.5-2 cm), smoking status (never, former, current) and histology (squamous, adenocarcinoma, other). At the 7th of 11 planned interim analyses, the Alliance Data and Safety Monitoring Board recommended releasing the data to the principal investigator.
Results
Baseline demographic and clinical characteristics were well-balanced between the two arms of the trial and minimally invasive approaches were utilised for 80% of all resections. Dr. Altorki and researchers at participating sites followed patients for seven years and determined the non-inferiority significance boundary had not been crossed. For disease-free survival (DFS), the primary endpoint of the trial, the stratified hazard ratio (HR) was 1.01 (90%CI: 0.83-1.24, one-sided p= 0.0176 for non-inferiority). In the sub-lobar arm and the lobectomy arm, the five-year DFS rate was 63.6%, and 64.1%, respectively. A post-hoc exploratory subgroup analysis of DFS demonstrated that SLR was not inferior to lobectomy across all major clinical and demographic features including age, gender, tumour location within the lung, histology, smoking status, tumour size and performance status. For overall survival, the stratified HR was 0.95 (90%CI: 0.75-1.21, one-sided p= 0.014 for non-inferiority). In the SLR arm and the lobectomy arm, the five-year OS rate was 80.3% and 78.9%, respectively.
Disease recurrence was observed in 29.3% of patients undergoing lobar resection and in 30.4% of patients undergoing SLR (p= 0.8364), without significant difference between arms in the incidence of isolated locoregional or systemic recurrence. The median change from baseline in FEV1 was -6.0 in the lobectomy arm and -4.0 in the SLR arm (p= 0.0006). In addition, also the absolute difference in the magnitude of reduction in FVC favoured the SLR arm (-5 vs. -3, p= 0.0712). However, it is unclear whether these are clinically meaningful.
Conclusion
In patients with peripheral cT1aN0 NSCLC ≤2 cm without metastases to major hilar and mediastinal lymph nodes, sub-lobar resection was not inferior to lobectomy for the primary endpoint of DFS or the secondary endpoint of overall survival. Disease recurrence was observed in approximately 30% of patients without significant difference between arms in the incidence of isolated locoregional or systemic recurrence. Although the absolute difference in the magnitude of reduction in FEV1 & FVC favoured the SLR arm, it may not be clinically meaningful. The results of this trial and JCOG 0802 establish SLR as the standard of care for this subset of patients.
Reference
Altorki N, Wang X, Kozono D, et al. Lobar or sublobar resection for peripheral clinical stage IA ≤ 2 cm NSCLC: Results from an international randomized phase III trial (CALGB 140503 [Alliance]). Presented at IASLC WCLC 2022; Abstract PL03.06.
