Validation of the Novel International Association for the Study of Lung Cancer Grading System for Invasive Pulmonary Adenocarcinoma and Association With Common Driver Mutations

Introduction: We aimed to validate the use of the novel grading system proposed by the International Association for the Study of Lung Cancer pathology committee for prognosis stratification of invasive pulmonary adenocarcinomas (ADCs) in Chinese patients. Correlations between the grading system, common driver mutations, and adjuvant chemotherapy (ACT) were also investigated.

Methods: From 2008 to 2016, the histologic patterns of a large cohort of 950 patients with invasive ADCs (stage I-III) were retrospectively analyzed and classified according to the proposed grading system. Subsequently, tumor grading was correlated with genetic data, ACT, and patient outcome.

Results: Compared with conventional predominant pattern-based groups, the novel grading system carried improved survival discrimination (area under the curve = 0.768 for recurrence-free survival and 0.775 for overall survival). The area under the curve was not further improved when incorporated lymphovascular invasion status. EGFR mutations (p < 0.001) were correlated with moderate grade, whereas KRAS mutations (p = 0.041) and ALK fusions (p = 0.021) were significantly more prevalent in poor grade. The reclassification of the grading system based on EGFR mutation status revealed excellent survival discrimination (p < 0.001). In particular, patients on stage Ib to III with novel high-grade ADCs had an improved prognosis with ACT.

Conclusions: The novel International Association for the Study of Lung Cancer grading system is a practical and efficient discriminator for patient prognosis and should be part of an integrated pathologic-genetic subtyping to improve survival prediction. In addition, it may support patient stratification for aggressive adjuvant chemotherapy.