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.