The additive effect of high-risk tumor features on long-term survival and recurrence in pathologic stage I non-small cell lung cancer.

Abstract

The standard of care for stage I non-small cell lung cancer (NSCLC) is curative-intent surgical resection without adjuvant therapy. However, many patients experience recurrence or death after surgery. This study aimed to assess the impact of high-risk tumor features in patients with stage I NSCLC. We performed a retrospective study of patients with completely resected pathologic stage I NSCLC measuring <3 cm (N = 847). The impact of high-risk features (positron emission tomography maximum standardized uptake value, lymphovascular invasion [LVI], and visceral pleural invasion [VPI]) and their additive effect was analyzed for overall survival (OS) using Cox proportional hazards models and for recurrence using Fine-Gray competing-risk models. In univariate analysis, high maximum standardized uptake value was associated with recurrence (hazard ratio, 2.46; 95% CI, 1.71-3.55) and reduced OS (hazard ratio, 2.23; 95% CI, 1.45, 3.52); LVI was associated with recurrence (hazard ratio, 2.59; 95% CI, 1.51-4.45) and reduced OS (hazard ratio, 2.96; 95% CI, 1.68-5.22); VPI was also associated with recurrence (hazard ratio, 1.63; 95% CI, 1.02-2.60) and reduced OS (hazard ratio, 1.76; 95% CI, 1.18-2.63). The association between LVI and mortality was robust in multivariate analysis (hazard ratio, 3.23; 95% CI, 1.05-5.92). There was an additive effect with the presence of 1, 2, and 3 high-risk features associated with recurrence (hazard ratio, 2.13; 95% CI, 11.41-3.22, hazard ratio, 2.79; 95% CI, 1.61-4.82, and hazard ratio, 7.08; 95% CI, 2.87-17.50, respectively). Similarly, 1, 2, and 3 high-risk features were associated with reduced OS (hazard ratio, 1.81; 95% CI, 1.09-3.00, hazard ratio, 2.50; 95% CI, 1.34-4.66, and hazard ratio, 6.29; 95% CI, 2.41-16.41). High-risk tumor features are significantly and cumulatively associated with postresection recurrence and mortality in pathologic stage I NSCLC. Although external validation is necessary, the presence of multiple high-risk features can identify patients at increased risk for worse outcomes. Future adjuvant therapy clinical trials should focus on these patients.