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. 2020 Mar;15(3):371-382.
doi: 10.1016/j.jtho.2019.11.009. Epub 2019 Nov 26.

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

Raymond U Osarogiagbon  1 , Nicholas R Faris  2 , Walter Stevens  2 , Carrie Fehnel  2 , Cheryl Houston-Harris  2 , Philip Ojeabulu  2 , Olawale A Akinbobola  2 , Yu-Shen Lee  3 , Meredith A Ray  3 , Matthew P Smeltzer  3
Affiliations

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

Raymond U Osarogiagbon et al. J Thorac Oncol. 2020 Mar.

Abstract

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.

Keywords: Complete; Incomplete; Lung cancer; Lymph node; Resection margin; Staging.

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Figures

Figure 1.
Figure 1.
Cohort survival stratified by IASLC R classification: complete; uncertain; and incomplete. ‘R-incomplete’ combines microscopically and grossly incomplete resections. Hazard ratio adjusted for: age at surgery, sex, race, primary insurance, histology, extent of resection, total comorbidities, and pathologic T-category.
Figure 2.
Figure 2.
Survival stratified by IASLC R classification: A.) pathologic N0 resections; B.) pathologic node-positive resections. ‘R-incomplete’ combines microscopically and grossly incomplete resections. Hazard ratio adjusted for: age at surgery, sex, race, primary insurance, histology, extent of resection, total comorbidities, and pathologic T-category.
Figure 2.
Figure 2.
Survival stratified by IASLC R classification: A.) pathologic N0 resections; B.) pathologic node-positive resections. ‘R-incomplete’ combines microscopically and grossly incomplete resections. Hazard ratio adjusted for: age at surgery, sex, race, primary insurance, histology, extent of resection, total comorbidities, and pathologic T-category.
Figure 3.
Figure 3.
Survival of IASLC R0 resection patients with systematic v lobe-specific nodal dissection.
Figure 4.
Figure 4.
Survival of patients with positive highest mediastinal lymph node station v R0- with positive mediastinal lymph node v R-uncertain with positive ‘other than highest’ mediastinal lymph node station.
Figure 5.
Figure 5.
Survival of cohort with R-uncertain category stratified by quality of nodal evaluation.
Figure 5.
Figure 5.
Survival of cohort with R-uncertain category stratified by quality of nodal evaluation.
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