Sublobar Resection Noninferior to Lobectomy in Terms of DFS Among Patients with Small Peripheral NSCLC and Pathologically Confirmed Node-Negative Disease

In a large, randomised study conducted in patients with small (≤2 cm), peripheral non-small cell lung cancer (NSCLC), clinical stage T1aN0, sublobar resection was noninferior to lobectomy with respect to study primary endpoint of disease-free survival (DFS). Overall survival (OS), secondary endpoint, was similar with the two procedures. The results of post hoc exploratory analyses that examined the association between relevant demographic and clinical variables and DFS and OS were consistent with the overall results. No substantial difference between the two groups was seen in the incidences or patterns of disease recurrence. The findings are published by Dr. Nasser Altorki of the Weill Cornell Medicine, New York–Presbyterian Hospital in New York, NY, US and colleagues on 9 February 2023 in The New England Journal of Medicine.

The authors wrote in the background that in 1995, the Lung Cancer Study Group reported the results of a randomised study comparing lobectomy with sublobar resection in patients with clinical stage T1N0 NSCLC. The frequency of local recurrence was 3x higher with sublobar resection as with lobectomy, and lung cancer–related mortality was 50% higher with sublobar resection. These results established lobectomy as the standard of surgical care for patients with clinical T1N0 NSCLC.

However, advances in imaging and staging since then have allowed the detection of smaller and earlier tumours. Japanese investigators recently reported the results of a large, randomised JCOG0802 study comparing lobectomy with anatomical segmentectomy in patients with clinical stage IA NSCLC with a tumour size of 2 cm or less. After a median follow-up of approximately 7 years, anatomical segmentectomy was superior to lobectomy for OS (primary endpoint) and noninferior to lobectomy for relapse-free survival.

The increased detection of small-sized peripheral NSCLC has renewed interest in sublobar resection. The CALGB 140503 investigators conducted a multicentre, international noninferiority, phase III study in which patients with NSCLC clinically staged as T1aN0 with tumour size ≤2 cm were randomly assigned to undergo sublobar or lobar resection after intraoperative confirmation of node-negative disease. The primary endpoint was DFS, defined as the time between randomisation and disease recurrence or death from any cause. Secondary endpoints were OS, locoregional and systemic recurrence, and pulmonary functions.

From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for DFS (hazard ratio [HR] for disease recurrence or death 1.01, 90% confidence interval [CI] 0.83 to 1.24). Furthermore, OS after sublobar resection was similar to that after lobar resection (HR for death 0.95, 95% CI 0.72 to 1.26).

The 5-year DFS was 63.6% (95% CI 57.9 to 68.8) after sublobar resection and 64.1% (95% CI 58.5 to 69.0) after lobar resection. The 5-year OS was 80.3% (95% CI 75.5 to 84.3) after sublobar resection and 78.9% (95% CI 74.1 to 82.9) after lobar resection.

No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. Locoregional recurrences were slightly numerically higher after sublobar resection than after lobectomy (13.4% vs. 10.0%). Although the study team did not mandate the extent of lymph node dissection beyond sampling of major hilar and two mediastinal nodal stations, regional recurrence occurred in 1.8% of the patients after sublobar resection and 2.6% of the patients after lobectomy.

At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favouring the sublobar resection group.

The authors stated that it is important that these results are interpreted strictly within the constraints of the eligibility criteria mandated by the study. These results will become increasingly relevant as the proportion of patients with early-stage NSCLC increases with expanded implementation of lung cancer screening and as the number of older persons with early-stage disease in whom sublobar resection may be the preferred surgical option increases. Another proposed benefit of sublobar resection is preservation of pulmonary function as measured by expiratory flow rates.

Regardless of the differences in study design, the concordance of results between the CALGB 140503 and JCOG0802 is reassuring. Together, these findings affirm that sublobar resection for patients with clinical T1aN0 disease by either anatomical segmentectomy or wedge resection is an effective management approach for this subgroup of patients with NSCLC.

In an accompanied editorial article, Dr. Valerie W. Rusch of the Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center in New York, NY, US wrote that although all these operations are now safe, sublobar resection is associated with an even lower risk than lobectomy. Patients who are cured of their first NSCLC remain at high risk for metachronous primary NSCLC and sublobar resections leave open more treatment options for such patients. The editorialist advocates that safeguards must be preserved in routine practice: thoracic surgeons will need to expand their expertise in sublobar resections, especially complex segmentectomies, and will need to collaborate closely with pathologists in assessing margins of resection, adequacy of lymph node staging, and tumour characteristics that may predict recurrence. When appropriate, lobectomy should still be performed, but the era of ‘precision’ surgery for NSCLC has arrived.

The study was supported by the US National Cancer Institute of the National Institutes of Health awards provided to the Alliance for Clinical Trials in Oncology and to the Canadian Cancer Trials Group, and in part supported by Covidien (formerly Tyco Healthcare) and Ethicon.