Histologic subtyping in pathologic stage I-IIA lung adenocarcinoma provides risk-based stratification for surveillance

Background: We hypothesize that recurrence hazard following resection for stage I-IIA lung adenocarcinoma (ADC) varies according to histologic subtype, which may provide risk stratification for surveillance better than the current uniform follow-up protocol. Results: Presence (≥5%) of high-grade histologic subtypes (MIP and/or SOL) was associated with a significantly higher recurrence hazard: (1) presence of either MIP or SOL was associated with a significant increase in recurrence hazard during the first two years after surgery; (2) presence of SOL was associated with an increase in recurrence hazard-in particular, distant recurrence hazard-during the first year after surgery; (3) absence of high-grade subtypes (515/1,572 patients) was associated with a very low recurrence hazard (<2% risk/year) during the first ten years after surgery. Methods: All hematoxylin and eosin-stained tumor slides from pathologic stage I-IIA lung ADC (n = 1572) were reviewed for quantification of the percentage of each histological subtype. Recurrence hazard was estimated using the Kernel-Epanechnikov smoothing procedure. The association between recurrence hazard and high-grade histologic subtypes (micropapillary [MIP] and solid [SOL]) was assessed. Conclusions: Our findings suggest that histologic subtyping has utility for identifying recurrence hazard for surgically resected stage I-IIA lung ADC patients and provide rationale for establishing risk-based surveillance.