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Guideline-Concordant Lymph Node Sampling Does Not Increase Complications After NSCLC Resection

By: Wendy LaGrego
Posted: Friday, August 14, 2026

A large retrospective cohort study published in JAMA Network Open found that adherence to the current guideline-recommended lymph node sampling strategy during surgical resection for early-stage non–small cell lung cancer (NSCLC) was not associated with an increased risk of postoperative complications. Led by Isheeta Madeka, MD, of Thomas Jefferson University Hospital, Philadelphia, the study provides evidence supporting the safety of the National Comprehensive Cancer Network (NCCN) and American College of Surgeons Commission on Cancer (ACS-CoC) recommendation for station-based lymph node sampling.

Background and Study Methods

Accurate lymph node staging is essential in early-stage NSCLC because it guides prognosis and selection of adjuvant therapies. Current NCCN and ACS-CoC guidelines recommend sampling at least 3 mediastinal (N2) and 1 hilar (N1) nodal stations, known as the "3 + 1 rule." Although this approach offers oncologic benefits, concerns have persisted that more extensive sampling could increase postoperative morbidity.

The investigators analyzed data from the Society of Thoracic Surgeons General Thoracic Database, identifying 28,439 patients (median age = 69 years, interquartile range = 66–75 years) with clinical stage T1 to T3, N0, M0 NSCLC who underwent surgical resection with documented lymph node sampling between July 2021 and January 2023. The primary endpoint was postoperative complications, including overall postoperative events, atrial arrhythmia, pleural effusion requiring drainage, pneumonia, and respiratory failure, among others. To minimize confounding, the investigators performed a 1:1 propensity score–matched analysis adjusting for demographic, clinical, and surgical characteristics.

Key Results

Overall, 18,939 patients (66.6%) met the 3 + 1 sampling criteria. Before matching, patients who underwent guideline-concordant sampling had longer median operative times (224 vs 210 minutes, P < .001) and higher rates of pathologic upstaging (13.3% vs 9.7%, P < .001). However, these differences were no longer significant after propensity matching.

The matched cohort included 4,029 patients in each group. Overall postoperative complication rates were nearly identical among patients who did and did not meet the 3 + 1 criteria (29.5% vs 30.0%; P = .33). Likewise, no significant differences were observed in individual complications, including atrial arrhythmias (7.1% vs 7.0%), prolonged air leak (11.5% vs 11.6%), pneumonia (2.3% vs 2.4%), respiratory failure (1.3% vs 1.7%), pulmonary embolism (0.5% vs 0.3%), or sepsis (0.7% vs 0.5%). Median hospital length of stay was 3 days in both groups, with no differences in operative duration, 30-day readmission (7.1% vs 7.4%), or pathologic upstaging after matching. Although mean length of stay and 30-day mortality differed slightly, the investigators considered these findings clinically insignificant.

"This study found that the 3 + 1 rule was not associated with increased postoperative complications in a matched cohort of patients with early-stage NSCLC who underwent lung resection," the authors concluded, although they emphasized that additional studies are needed to determine its effects on long-term survival and recurrence.

DISCLOSURE: This study was funded by the Department of Surgery at Thomas Jefferson University Hospital, Philadelphia. For full disclosures of the study authors, visit jamanetwork.com.


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