The prognostic value of visceral pleural infiltration in ≤3cm non-small cell lung cancer presenting with ground glass opacity: An inverse probability of treatment weighting study

Background: Visceral pleural infiltration (VPI) has been identified as an important risk factor in non-small cell lung cancer (NSCLC) for many decades. However, for patients who present with ground glass opacity (GGO), the prognostic value of VPI is still elusive. We aimed to investigate whether the VPI is a significant prognostic factor in surgically resected ≤3 cm stage I NSCLC who presented with GGO. Materials and methods: Patients with primary NSCLC who underwent surgical resection between December 2009 and December 2018 were collected. Stage I tumors that presented as GGO nodule with a tumor size of less than 3 cm were included and divided into two groups based on VPI status (positive and negative). Clinical, pathological, and prognostic data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using the Cox proportional hazards model and Kaplan-Meier method. Results: A total of 2043 patients were included in this study (VPIs were found in 196 patients). After IPTW weighting, all factors between the two groups were balanced. The median follow-up time was 67.3 months. According to the multivariable Cox models, the VPI was not a significant prognostic factor for OS (HR = 2.00, 95% CI, 0.96-4.17; P = 0.063), but was significant for RFS (HR =2.00, 95% CI, 1.12-3.55; P = 0.019). In subgroup analysis, we found VPI was significant for OS (HR=3.17, 95%CI: 1.09-9.26, P =0.035) and RFS (HR=4.07, 95%CI: 1.76-9.40, P =0.001) in patients with a tumor size >1 cm and a consolidation to tumor ratio (CTR) >50%. For patients with a tumor size ≤1 cm or a CTR ≤50%, the VPI was not significant. Conclusions: VPI may be a significant risk factor for GGOs in NSCLC patients with a tumor size >1 cm and a CTR >50%. Further prospective studies conducted across multi-centers with a larger sample size are needed.