Beyond Margin Status: Population-Based Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification Recategorization.

INTRODUCTION: The International Association for the Study of Lung Cancer's (IASLC's) proposal to recategorize the residual tumor (R) classification for resected NSCLC needs validation.
METHODS: Using a 2009 to 2019 population-based multi-institutional NSCLC resection cohort from the United States, we classified resections by Union for International Cancer Control (UICC) and IASLC R criteria and compared the distribution of R classification variables and their survival associations.
RESULTS: Of 3361 resections, 95.3% were R0, 4.3% were R1, and 0.4% were R2 by UICC criteria; 33.3% were R0, 60.8% were R-uncertain, and 5.8% were R1/2 by IASLC criteria; 2044 patients (63.8%) migrated from UICC R0 to IASLC R-uncertain. Median survival was not reached, 69 (95% confidence interval [CI]: 64-77), and 25 (95% CI: 18-36) months, respectively, for patients with IASLC R0, R-uncertain, and R1 or R2 resections. Failure to achieve nodal dissection criteria caused 98% of migration to R-uncertainty, metastasis to the highest mediastinal node station, 5.8%. Compared with R0, R-uncertain resections with mediastinal nodes, no mediastinal nodes, and no nodes had adjusted hazard ratios of 1.28 (95% CI: 1.10-1.48), 1.47 (95% CI: 1.24-1.74), and 1.74 (95% CI: 1.37-2.21), respectively, suggesting a dose-response relationship between nodal R-uncertainty and survival. Accounting for mediastinal nodal involvement, the highest mediastinal station involvement was not independently prognostic. The incomplete resection variables were uniformly prognostic.
CONCLUSIONS: The proposed R classification recategorization variables were mostly prognostic, except the highest mediastinal nodal station involvement. Further categorization of R-uncertainty by severity of nodal quality deficit should be considered.