Novel biologic factors correlated to visceral pleural invasion in early-stage non-small cell lung cancer less than 3 cm.

Background: Visceral pleural invasion (VPI) in early-stage non-small cell lung cancer (NSCLC) is traditionally believed as the result of too much close distance between cancerous lesion and the visceral pleura, but whether there are any other biologic factors correlated to VPI beyond our instinctive thoughts remains unclear. Therefore, we conducted this study to investigate potential factors correlated to VPI comprehensively.

Methods: Both clinical and pathological characteristics of patients undergoing surgery for NSCLC with a size of ≤3 cm were retrospectively analysed.

Results: A total of 403 patients were included for analysis. Patients with VPI had older age than those without (61.1 vs. 56.1 years; P<0.001). The mean size of NSCLCs with VPI was larger than those without (2.1 vs. 1.6 cm; P<0.001). Moreover, NSCLCs with VPI were located closer to visceral pleura (0.8 vs. 1.3 cm; P<0.001) and showed larger rates of pleural indentation (86.8% vs. 45.6%; P<0.001) and spiculation (59.7% vs. 34.7%; P<0.001) than those without. Pathologically, NSCLCs with VPI tended more likely to be adenocarcinomas (96.9% vs. 92.7%; P=0.097), and was more likely to be poorly differentiated (38.0% vs. 15.3%; P<0.001), to have cancer embolus (6.2% vs. 0.7%; P=0.001) and lymph node metastasis (29.5% vs. 10.2%; P<0.001) than those without. Besides shorter distance to visceral pleura [odds ratio (OR)=2.169, 95% CI: 1.221-3.855; P=0.008], older age [OR =2.119, 95% confidence interval (CI): 1.255-3.503; P=0.005], pleural indentation (OR =3.679, 95% CI: 1.888-7.169; P<0.001), adenocarcinoma (OR =4.741, 95% CI: 1.383-16.255; P=0.013), and poor tumor differentiation (OR =11.816, 95% CI: 4.470-31.234; P<0.001) were also found to be closely correlated to VPI in early-stage NSCLC.

Conclusions: Besides shorter distance to visceral pleura and pleural indentation, elderly, adenocarcinoma, and poor tumor differentiation were novel biologic factors correlated to VPI in early-stage NSCLC, which may explain why VPI was an unfavorable prognostic factor for early-stage NSCLC.