After a nearly 20-year wait, the results are finally in: sublobar surgery has been found to be noninferior to lobectomy and may be the new standard of care of patients with small, early-stage non–small cell lung cancer (NSCLC). Results of the phase III Alliance trial, presented at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer, showed a 5-year disease-free survival of 63.6% for patients with NSCLC tumors up to 2 cm who were randomly assigned to undergo sublobar resection, compared with 64.3% for those who had lobar resection (hazard ratio [HR] = 1.01).1 Study authors also reported noninferiority with respect to recurrence rate and overall survival for sublobar vs lobar resection.
“The results ofthe trial, combined with results from the JCOG 0802/WJOG 4607L trial released earlier this year, establish sublobar resection as the standard of care for patients with peripheral cT1aN0 NSCLC (≤ 2 cm) without metastases to major hilar and mediastinal lymph nodes,” said lead study author Nasser Altorki, MD, Professor of Cardiothoracic Surgery and Director of the Division of Thoracic Surgery at NewYork-Presbyterian/Weill Cornell Medical Center, New York.
Nasser Altorki, MD
As Dr. Altorki explained, resection of the entire lobe has been the surgical standard of care for cT1aN0 NSCLC since 1995, but this approach has been questioned due to better imaging, improved staging, and increased screening. Results of a recent, larger randomized trial in Japan (JCOG 0802/WJOG 4607L) showed that segmentectomy, a type of sublobar resection, is equivalent to lobectomy.2
Study Methods and Endpoints
Dr. Altorki and colleagues began recruiting patients for the multicenter, noninferiority phase III Alliance trial (CALGB 140503) in 2007 and completed accrual in 2017. The investigators randomly assigned patients with NSCLC (clinically staged as T1aN0 with tumor measuring ≤ 2 cm) to lobar or sublobar resection.
To be eligible for the study, patients had to have pathologically confirmed NSCLC and node-negative disease at level 10, as well as up to two mediastinal stations prior to randomization. Of the 1,080 patients enrolled, 697 patients were intraoperatively assigned randomly to either lobar (357 patients) or sublobar (340 patients) resection.
The primary endpoint was disease-free survival. Secondary endpoints included overall survival and the difference in pulmonary functions at 6 months postoperatively betweenthe treatment arms. Minimally invasive approaches such as video-assisted thoracoscopic surgery were used for 80% of all resections.
As Dr. Altorki reported, the study met its primary endpoint. Disease-free survival at 5 years for sublobar resection (63.9%) was found to be noninferior to lobar resection (64.3%), and the rates of recurrence or death from lung cancer were also overlapping.
Subgroup analysis showed no difference in disease-free survival regarding various clinical factors, including age, sex, and histology. Of note, said Dr. Altorki, stratification based on tumor size also showed no difference in outcomes.
With respect to the secondary endpoint of overall survival, sublobar resection was again found to be noninferior to lobar resection (HR = 0.95). The 5-year overall survival rate was 80% with sublobar resection vs 78% with lobar resection. “There may even be an overall survival advantage to sublobar resection, but we could not show that in our trial,” said Dr. Altorki. “However, the Japanese study definitely showed an advantage.”
The 30- and 90-day mortality rates were 1.1% and 1.7% after lobar resection and 0.6% and 1.2% after sublobar resection, respectively.
Finally, analysis of forced expiratory volume and idle capacity showed some preservation of pulmonary function with sublobar vs lobar resection. However, Dr. Altorki noted that the difference was not as large as expected. “I think we may have looked at the wrong metrics here,” he hypothesized. “Functional metrics like the 6-minute walk test and pulmonary exercise testing might have been able to detect a greater difference.”
Nevertheless, Dr. Altorki underscored the strong evidence in favor of sublobar resection in this cohort of highly selected patients. “Sublobar resection is safe, advisable, and in fact the new standard of care,” he concluded.
DISCLOSURE: Dr. Altorki disclosed financial relationships with AstraZeneca, Janssen Pharmaceuticals, New York Genome Center, and Regeneron.
REFERENCES
1. Altorki NK, Wang X, Kozono D, et al: Lobar or sublobar resection for peripheral clinical stage IA = 2 cm non-small cell lung cancer: Results from an international randomized phase III trial (CALGB 140503 [Alliance]). 2022 World Conference on Lung Cancer. Abstract PL03.06. Presented August 8, 2022.
2. Konno H, Ohde Y: [Current status of limited resection for lung cancer as minimally invasive surgery]. Kyobu Geka 72:51-56, 2019.
