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Association of Lymph Node Sampling Criteria on Pathologic Nodal Upstaging, Short-Term Recurrence-Free Survival, and Overall Survival in Patients with Non-Small Cell Lung Cancer
Ryan C. Jacobs1, Raheem D. Bell1, Maxime A. Visa1, Austin B. Chang1, Kelley Chan2, Jonathan E. Williams3, Kalvin C. Lung1, *Samuel S. Kim1, Ankit Bharat1, David J. Bentrem1, David D. Odell3
1Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States, 2Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States, 3Surgery, University of Michigan, Ann Arbor, Michigan, United States
Background: General lymph node and lobe-specific sampling criteria have been proposed for optimal intraoperative lymph node assessment during curative intent lung cancer resections. Oncologic outcomes by lymph node sampling criteria across anatomic lobes and clinical stages of disease have not been compared. This study evaluates the association of lymph node sampling criteria on pathologic nodal upstaging, recurrence-free survival, and overall survival for patients with non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective cohort analysis using data from a single health system for patients with non-metastatic NSCLC undergoing elective first-time operations from 2018-2023. Patients were categorized into those meeting general lymph node sampling criteria per American College of Surgeons Commission on Cancer (ACS CoC) guidelines (3 N2 and 1 N1 station sampled), those meeting lobe specific sampling criteria per European Society for Thoracic Surgeons (ESTS) guidelines (right upper and middle lobes: 2R, 4R, & 7; right lower lobe: sampling of 4R, 7, 8, & 9; left upper lobe: sampling of 5, 6, & 7; left lower lobe: sampling of stations 7, 8, & 9), or meeting neither criteria across all anatomic lobes and clinical stages of disease. Patients meeting lobe-specific sampling criteria only were excluded as only 3 patients met this criterion. We performed multivariable logistic regression to evaluate pathologic nodal upstaging, multivariable Fine and Gray competing risks modeling to evaluate recurrence-free survival, and multivariable Cox proportional hazard modeling to evaluate overall survival by lymph node sampling criteria. Results: Of 961 total patients, 406 (42.3%) met general lymph node sampling criteria (ACS CoC), 118 (12.3%) met general lymph node sampling and lobe-specific sampling criteria (ACS CoC+ESTS), and 437 (45.5%) met neither lymph node sampling criteria. Clinical T1N0 NSCLC comprised 247 (60.9%) meeting ACS CoC criteria, and 66 (55.9%) meeting ACS CoC+ESTS sampling criteria, and 305 (69.8%) of patients meeting neither lymph node sampling criteria (p<0.001). Unadjusted rates of pathologic nodal upstaging were 13.0% for patients meeting ACS CoC sampling criteria, 11.2% for patients meeting ACS CoC+ESTS sampling criteria, and 7.9% for patients meeting neither lymph node sampling criteria (p=0.060). After adjusting for covariates, compared to patients meeting ACS CoC sampling criteria, patients meeting ACS CoC+ESTS sampling criteria had no significant difference in odds of identifying pathologic nodal upstaging (aOR 0.69 95% CI [0.32-1.48]), and patients meeting neither lymph node sampling criteria had a 51% lower odds of identifying pathologic nodal upstaging (aOR 0.49 95% CI [0.31-0.78]). Compared to patients meeting ACS CoC sampling criteria, no significant differences were observed between patients meeting ACS CoC+ESTS sampling criteria or neither criteria in recurrence-free survival (aSHR 1.28 95% CI [0.71-2.33], aSHR 1.11 [0.51-2.42]) or overall survival (aHR 1.03 95% CI [0.54-1.99], aHR 0.86 95% CI [0.48-1.53]). Conclusions: Patients who meet lobe-specific sampling criteria often meet general lymph node sampling criteria. Lobe-specific sampling criteria does not offer a difference in identifying pathologic nodal upstaging compared to a general lymph node sampling criteria, with no differences in recurrence-free or overall survival observed. When considering dissemination of lymph node sampling guidelines on a national scale, a general lymph node sampling strategy may be sufficient when considering optimizing intraoperative lymph node assessment for oncologic outcomes.
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