Vascular Invasion Predicts Recurrence in Stage IA2-IB Lung Adenocarcinoma but not Squamous Cell Carcinoma

NCCN-guidelines list vascular invasion (VI) as a risk-factor warranting consideration of adjuvant therapy among stage IB NSCLC. Among resected stage IA2-IB LUAD (n =344) and LUSC (n =102), VI predicted worse 5-year RFS for LUAD (64% vs. 90%, P <0.001) but not LUSC (83% vs. 80%, P =0.852). Guidelines should be modified to specify VI as a risk-factor only for stage I adenocarcinoma. Background: Lymphovascular invasion (LVI) is an adverse prognostic feature in resected stage I non-small cell lung cancer (NSCLC); however, it is unclear if the prognostic significance applies to both lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Materials and Methods: A retrospective review of H&E-stained slides from surgically resected AJCC 8th ed. stage IA2-IB LUAD (n = 344) and LUSC (n = 102) from two institutions was performed. LVI was defined as either lymphatic (LI) or vascular (VI) invasion. Outcomes were assessed by 5-year recurrence-free survival (RFS) estimates using the Kaplan-Meier method. Results: The cohorts of LUAD and LUSC showed no significant differences in 5-year RFS (81% each), stage, age, race, or surgical procedure. The presence of LVI, VI, and LI was predictive of 5-year RFS for LUAD (LVI + 71% vs. LVI -92%, P < 0.001; VI + 64% vs. VI -90%, P < 0.001; LI + 75% vs. LI -84%, P = 0.030) but not LUSC (LVI + 84% vs. LVI -79%, P = 0.740; VI + 83% vs. VI-80%, P = 0.852; LI + 84% vs. LI -81%, P = 0.757). Among LUAD with LVI, VI was a stronger predictor of 5-year RFS than the remaining subset of VI-LI + tumors (64% vs. 87%, P = 004). Subset analysis of LI among LUAD stratified by VI showed no significant prognostic advantage to adding LI for risk stratification (VI-LI + 87% vs. VI-LI -92%, P = 0.347 & VI + LI + 62% vs. VI + LI-66%, P = 0.422). VI was present in 36% of LUAD. Conclusion: Vascular invasion is a strong predictor of recurrence in stage IA2-IB LUAD but not in LUSC. Adjuvant therapy trials should be directed at this subgroup.