Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases

A new lung adenocarcinoma classification is being proposed by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS). This proposal has not yet been tested in clinical datasets to determine whether it defines prognostically significant subgroups of lung adenocarcinoma. In all, 514 patients who had pathological stage I adenocarcinoma of the lung classified according to the Union for International Cancer Control/American Joint Committee on Cancer 7th Edition, and who had undergone a lobectomy with mediastinal lymph node dissection were retrospectively reviewed. Comprehensive histological subtyping was used to estimate the percentage of each histological subtype and to identify the predominant subtype. Tumors were classified according to the proposed new IASLC/ATS/ERS adenocarcinoma classification. Statistical analyses were made including Kaplan-Meier and Cox regression analyses. There were 323 females (63%) and 191 males (37%) with a median age of 69 years (33-89 years) and 298 stage IA and 216 stage IB patients. Three overall prognostic groups were identified: low grade: adenocarcinoma in situ (n=1) and minimally invasive adenocarcinoma (n=8) had 100% 5-year disease-free survival; intermediate grade: non-mucinous lepidic predominant (n=29), papillary predominant (n=143) and acinar predominant (n=232) with 90, 83 and 84% 5-year disease-free survival, respectively; and high grade: invasive mucinous adenocarcinoma (n=13), colloid predominant (n=9), solid predominant (n=67) and micropapillary predominant (n=12), with 75, 7170 and 67%, 5-year disease-free survival, respectively (P < 0.001). Among the clinicopathological factors, stage 1B versus 1A (P<0.001), male sex (P<0.008), high histological grade (P<0.001), vascular invasion (P=0.002) and necrosis (P<0.001) were poorer prognostic factors on univariate analysis. Both gross tumor size (P=0.04) and invasive tumor size adjusted by the percentage of lepidic growth (P<0.001) were significantly associated with disease-free survival with a slightly stronger association for the latter. Multivariate analysis showed the prognostic groups of the IASLC/ATS/ERS histological classification (P=0.038), male gender (P=0.007), tumor invasive size (P=0.026) and necrosis (P=0.002) were significant poor prognostic factors. In summary, the proposed IASLC/ATS/ERS classification of lung adenocarcinoma identifies histological categories with prognostic differences that may be helpful in identifying candidates for adjunctive therapy. The slightly stronger association with survival for invasive size versus gross size raises the need for further studies to determine whether this adjustment in measuring tumor size could impact TNM staging for small adenocarcinomas. Modern Pathology (2011) 24, 653-664; doi:10.1038/modpathol.2010.232; published online 21 January 2011