SUMMARY: The American Cancer Society estimates that for 2022, about 236,740 new cases of lung cancer will be diagnosed and 135,360 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers and Adenocarcinoma now is the most frequent histologic subtype of lung cancer.
Lobectomy is the standard of care for early-stage resectable Non-Small Cell Lung Cancer (NSCLC). Pneumonectomy is rarely performed due to unacceptably high mortality rate. Sublobar resection (Wedge resection or Segmentectomy) is considered a “compromise operation” in selected high risk patients with early stage lung cancer. With the approval of lung cancer screening in high risk individuals and subsequent detection of small tumors, Sublobar resections have been on the rise, even in good-risk patients in many institutions. Sublobar resection includes wedge resection and segmentectomy. In wedge resection, the lung tumor is removed with a surrounding margin of normal lung tissue, and is not an anatomical resection. Segmentectomy, unlike wedge resection, is an anatomical resection that usually includes one or more pulmonary parenchymal segments with the dissection of intraparenchymal and hilar lymph nodes. Wedge resection is inferior to anatomic segmentectomy and is associated with an increased risk of local recurrence and decreased survival in patients with Stage I NSCLC.
The clinical benefits and survival outcomes of segmentectomy have not been investigated in a randomized trial setting. The aim of this study was to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC. In this randomized, controlled, multicenter, non-inferiority trial, 1106 patients (intention-to-treat population) were enrolled in Japan between Aug, 2009 and Oct 2014, and were randomly assigned 1:1 to receive either lobectomy (N=554) or segmentectomy (N=552). Enrolled patients had clinical Stage IA NSCLC based on contrast-enhanced CT scan and had a single tumor 2 cm or less in diameter, not located in the middle lobe, the center of which was in the outer third of the lung field, with no evidence of lymph node metastasis. Patient baseline clinicopathological factors were well balanced between the two treatment groups. The Primary endpoint was Overall Survival and Secondary endpoints included postoperative respiratory function at 6 months and 12 months, Relapse-Free Survival, proportion of local relapse and adverse events.
At a median follow up of 7.3 years, the 5-year Overall Survival was 94.3% for segmentectomy and 91.1% for lobectomy. Both superiority and non-inferiority in Overall Survival were confirmed using a stratified Cox regression model (HR=0.663; one-sided P<0.0001 for non-inferiority and P=0.0082 for superiority). This improved Overall Survival benefit was observed consistently across all predefined subgroups in the segmentectomy group. At 1 year follow-up, the significant difference in the reduction of median FEV1 between the two treatment groups was 3.5% (P<0.0001), but this however did not reach the predefined threshold for clinical significance of 10%. The 5-year Relapse-Free Survival was 88% for segmentectomy and 87.9% for lobectomy and was not statistically significant. The probability of local recurrence was approximately doubled and was 10.5% for segmentectomy and 5.4% for lobectomy (P=0.0018). Postoperative complications of grade 2 or worse occurred at similar frequencies in both treatment groups.
The authors concluded that this study is the first Phase III trial to show Overall Survival benefit with segmentectomy, compared to lobectomy, in patients with small-peripheral NSCLC. They added that segmentectomy should be the standard surgical procedure for this population of patients.
Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Saji H, Okada M, Tsuboi M, et al. The Lancet 2022;399:1607-1617.
