Sublobar resection is noninferior to a full lobectomy in patients with carefully staged cT1aN0 non-small cell lung cancer (NSCLC), according to research presented at the IASLC 2022 World Conference on Lung Cancer.1
Based on these findings, researchers recommend that sublobar resection be offered to NSCLC patients with small peripheral tumors who do not have lymph node metastasis.
“The results of this trial and of JCOG 0802 establish sublobar resection as a new standard of care for this subset of patients,” said study presenter Nasser K. Altorki, MD, of Weill Cornell Medicine and NewYork-Presbyterian Hospital in New York, New York.
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Dr Altorki noted that lobar resection has been the standard procedure for patients with cT1N0 NSCLC since 1995, and sublobar resection has been reserved for patients with marginal pulmonary reserve.2
However, a recent phase 3 trial of NSCLC patients in Japan — the JCOG 0802 trial — showed that sublobar resection can produce superior overall survival (OS) in comparison with complete lobectomy for patients with tumors measuring 2 cm or smaller.3
Dr Altorki and colleagues conducted a similar phase 3 trial — CALGB 140503 — to compare lobar and sublobar resection in North American and Australian patients with cT1aN0 NSCLC tumors measuring 2 cm or smaller.1
CALGB 140503 Trial Details
The CALGB 140503 trial (ClinicalTrials.gov Identifier: NCT00499330) included 697 randomized patients with stage IA NSCLC. The patients were randomly assigned to lobar resection (357 patients) or sublobar resection (340 patients) after histologic confirmation of NSCLC and node-negative disease by frozen section examination of level 10 lymph nodes and at least 2 mediastinal stations.
Demographic and clinical characteristics (smoking status, histology, and tumor size) were well balanced between the 2 arms. A minority of the lobectomy arm (9.8%) and the sublobar resection arm (8.2%) had never been smokers. The tumor histology was adenocarcinoma in 63.3% and 64.1% of patients, respectively. Roughly 40% of patients in each arm (41.2% lobectomy and 40.6% sublobar resection) had tumors measuring 1.6-2.0 cm.
Among the patients assigned to undergo sublobar resection, the majority (58.8%) had wedge resections.
Noninferiority of Sublobar Surgery
The primary endpoint was disease-free survival (DFS). At a median follow-up of 7 years, DFS in patients treated with sublobar resection was noninferior to DFS in patients who had lobectomy.
The stratified hazard ratio (HR) for DFS was 1.01 (90% CI, 0.83-1.24; 1-sided P for noninferiority =.0176). The 5-year DFS rate was 63.6% for the sublobar arm and 64.1% for the lobar resection arm. There were no significant differences in DFS between the arms by tumor size or in the eventual sites of recurrence (locoregional, regional, distant, or combined sites).
For OS, the stratified HR was 0.95 (90% CI, 0.75-1.21; 1-sided P for noninferiority =.014). The 5-year OS rate was 80.3% with sublobar resection and 78.9% with lobar resection.
There were no significant differences between the arms with respect to lung cancer-related deaths (HR, 0.99; 95% CI, 0.74-1.33; P =.9521) and deaths from other causes (HR, 1.12; 95% CI, 0.75-1.68; P =.5897).
There was a significant difference from baseline in median forced expiratory volume in the first second (FEV1) between the lobectomy and sublobar resection arms (-6.0 and -4.0, respectively; P =.0006). However, the change in forced vital capacity (FVC) from baseline was not significantly different between the arms (-5 and -3, respectively; P =.0712).
Implications for Patients
Like the JCOG 0802 trial, the CALGB 140503 trial demonstrated noninferior DFS for sublobar resection in comparison with full lobectomy. The CALGB trial showed noninferior OS as well, but the JCOG 0802 trial showed superior OS with sublobar resection.
It is important to note, however, that there were some baseline differences between the 2 trial populations, said Hisashi Saji, MD, PhD, of St Marianna University School of Medicine in Kawasaki, Japan, who was invited to discuss the CALGB 140503 results at WCLC 2022.
The CALGB trial participants more often had squamous cell histology, were more likely to be current or former smokers, and had worse performance status, Dr Saji noted. These differences may explain the fact that CALGB participants had lower rates of 5-year DFS and OS, more locoregional recurrences, and more adverse events of grade 3 or higher.
Nevertheless, both trials demonstrated noninferiority for DFS, similar rates of grade 3 or higher adverse events between the treatment arms, and a roughly 3% difference in loco-regional recurrence between the arms.
Based on these findings, Dr Saji concluded that sublobar resection must be considered standard care for NSCLC patients with small peripheral tumors who do not have lymph node metastasis. He added that using sublobar resection in this patient group allows for the possibility of more extensive treatment for subsequent life-threatening diseases, such as second primary cancer, respiratory disease, or cerebrovascular disease.
Disclosures: Dr Altorki disclosed affiliations with AstraZeneca LLC, Janssen Pharmaceuticals, the New York Genome Center, and Regeneron. Dr Saji disclosed affiliations with Astellas Pharma, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharma, Covidien, Ethicon, Fujifilm Medical, Japan Blood Products Organization, Lilly, Merck Sharpe & Dohme, Novartis, Taiho, Teijin, Takeda Pharmaceutical Company Limited, and Yakult.
References
- Altorki NK, Wang X, Kozono D, et al. Lobar or sub-lobar resection for peripheral clinical stage IA = 2 cm NSCLC: Results from an international randomized phase III trial (CALGB 140503 [Alliance]). Presented at WCLC 2022. August 6-9, 2022. Abstract 3051.
- Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995;60(3):615-622; discussion 622-623. doi:10.1016/0003-4975(95)00537-u
- Saji H, Okada M, Tsuboi M, et al. 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. Lancet. 2022;399(10335):1607-1617. doi:10.1016/S0140-6736(21)02333-3
