3+1 Lymph Node Sampling Not Associated With Increased Postoperative Complications in NSCLC

Adhering to the current guideline standard for intraoperative nodal assessment in resected non–small cell lung cancer (NSCLC), commonly known as the 3+1 lymph node sampling (LNS) rule, was not associated with increased postoperative complications, according to a study recently published in JAMA Network Open.¹

Evolving Standards for LNS in Early-Stage NSCLC

For early-stage NSCLC, surgical resection with LNS is the standard of care, and accurate lymph node staging is considered essential for prognosis and treatment selection, including eligibility for emerging therapies. However, the definition of “adequate” LNS has evolved as evidence has accumulated.

Mediastinal lymph node dissection was previously considered standard, but the 2006 ACOSOG-Z0030 trial (NCT00003831) found no survival or recurrence advantage compared with mediastinal LNS in select early-stage patients.² This finding helped shift guideline recommendations toward less extensive but systematic nodal evaluation, including earlier proposals to sample a minimum number of lymph nodes.¹ Subsequent studies, however, showed inconsistent associations between the total number of nodes sampled and survival outcomes.

Current National Comprehensive Cancer Network (NCCN) and American College of Surgeons Commission on Cancer (ACS-CoC) guidelines instead emphasize a station-based approach, known as the “3+1 rule,” requiring sampling of at least 3 N2 (mediastinal) and 1 N1 (hilar) nodal stations. Despite growing adoption of this strategy, there is limited evidence on its real-world surgical impact, particularly regarding postoperative complications. Because of this, investigators assessed whether adherence to the 3+1 LNS rule is associated with increased postoperative morbidity.

3+1 Rule Not Associated With Increased Postoperative Morbidity

The analysis used data from the Society of Thoracic Surgeons General Thoracic Database, the largest clinical thoracic surgery registry in North America. Eligible patients included those with clinical stage T1 to T3, N0, or M0 NSCLC who underwent resection with known LNS between July 2021 and January 2023. The researchers used a 1:1 propensity score match to compare complication rates by 3+1 status, balancing 14 characteristics, including age, smoking history, T stage, surgical approach, and performance status.

The overall population included 28,439 patients. They had a median age of 69 years, 59.5% were female, and 66.6% satisfied the 3+1 rule. The match yielded 4029 pairs, well-balanced across demographics, comorbidities, histology, and surgical approach, with robotic-assisted surgery comprising 58% of procedures in each arm.

In the matched cohort, overall postoperative event rates were nearly identical between patients who met the 3+1 criteria and those who did not (29.5% vs 30.0%; P = .33). No individual complication, including atrial arrhythmia, air leak, pneumonia, respiratory failure, chylothorax, or recurrent laryngeal nerve injury, differed significantly between groups. Similarly, 30-day readmission rates were equivalent in both cohorts (7.1% vs 7.4%; P = .77).

Mean length of stay (LOS) was nominally shorter in the 3+1 group (4.0 vs 4.7 days; P < .001), though the authors noted that wide standard deviations make this difference clinically unreliable; median LOS was 3 days in both arms. In addition, pathologic upstaging, which appeared more frequent in the 3+1 arm before adjustment, was no longer significantly different after matching (10.8% vs 10.2%; P = .45), indicating the unadjusted signal had been driven by confounders such as the extent of resection.

Next Steps in 3+1 Guideline Research

The researchers acknowledged several study limitations, including residual confounding from unmeasured variables that may remain despite the use of propensity score matching to balance baseline covariates. They also used a retrospective database, which may introduce selection bias. Still, the researchers expressed confidence in their findings and used them to suggest areas for further research.

"This study's results support the use of the 3+1 rule in terms of overall safety profile for surgeons who elect to use station-based LNS, in concordance with current recommendations from the NCCN and ACS-CoC," the authors concluded. “Further research is needed to evaluate its effects on long-term survival and local and regional recurrence after implementation of the current recommendations.”

References

1. Madeka I, Noueihed K, Woodroof J, et al. Lymph node dissection and postoperative complications after lung cancer resection. JAMA Network Open. 2026;9(6):e2615894. doi:10.1001/jamanetworkopen.2026.15894
2. Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg. 2006;81(3):1013-1020. doi:10.1016/j.athoracsur.2005.06.066