Beyond Margin Status: Population-Based Validation of the Proposed IASLC Residual Tumor Classification Re-categorization

Abstract Introduction The International Association for the Study of Lung Cancer’s (IASLC’s) proposal to re-categorize the residual tumor (R) classification for resected non-small cell lung cancer needs validation. Methods Using a 2009-2019 population-based multi-institutional non-small cell lung cancer resection cohort from the United States, we classified resections by Union for International Cancer Control (UICC) and IASLC R criteria, compared the distribution of R classification variables and their survival associations. Results Of 3361 resections, 95.3% were R0, 4.3% R1 and 0.4% were R2 by UICC criteria; 33.3% were R0, 60.8% 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 (CI, 64-77), and 25 (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 to R0, R-uncertain resections with mediastinal nodes, no mediastinal nodes and no nodes had adjusted hazard ratios of 1.28 (CI, 1.10-1.48), 1.47 (CI, 1.24-1.74) and 1.74 (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, excepting highest mediastinal nodal station involvement. Further categorization of R-uncertainty by severity of nodal quality deficit should be considered.