Impact of a Lymph Node Specimen Collection Kit on the Distribution and Survival Implications of the Proposed Revised Lung Cancer Residual Disease Classification: A Propensity-Matched Analysis

IMPORTANCE: The International Association for the Study of Lung Cancer (IASLC) has proposed a revision of the residual disease (R-factor) classification, to R0, ‘R-uncertain’, R1 and R2. We previously demonstrated longer survival after surgical resection with a lymph node specimen collection kit, and now evaluate R-factor redistribution as the mechanism of its survival benefit. OBJECTIVE: We retrospectively evaluated surgical resections for lung cancer in the population-based observational ‘Mid-South Quality of Surgical Resection’ cohort from 2009-2019, including a full-cohort and propensity-score matched analysis. RESULTS: Of 3,505 resections, 34% were R0, 60% R-uncertain, and 6% R1 or R2. The R0 percentage increased from 9% in 2009 to 56% in 2019 (p < 0.0001). Kit cases were 66% R0 and 29% R-uncertain, compared to 14% R0 and 79% R-uncertain in non-kit cases (p < 0.0001). Compared with non-kit resections, kit resections had 12.3 times the adjusted odds of R0 versus R-uncertainty. Of 2,100 R-uncertain resections, kit cases had lower percentages of non-examination of lymph nodes, 1% vs. 14% (p < 0.0001) and non-examination of mediastinal lymph nodes, 8% vs. 35% (p < 0.0001). With the kit, more R-uncertain cases had examination of stations 7 (43% vs. 22%, p < 0.0001) and 10 (67% vs. 45%, p < 0.0001). The adjusted hazard ratio (aHR) for kit cases versus non-kit cases was 0.75 (confidence interval [CI]: 0.66–0.85, p < 0.0001). In 2,100 subjects with R-uncertain resections, kit cases had an aHR of 0.79 versus non-kit cases ([CI: 0.64–0.99], p=0.0384); however, in the 1,199 R0 resections the survival difference was not significant (aHR: 0.85[0.68–1.07], p = 0.17). CONCLUSIONS AND RELEVANCE: A lymph node kit increased overall survival by increasing R0, reducing the probability of R-uncertain resections, and diminishing extreme R-uncertainty.