Lymph but Not Blood Vessel Invasion Is Independent Prognostic in Lung Cancer Patients Treated by VATS-Lobectomy and Might Represent a Future Upstaging Factor for Early Stages

SIMPLE SUMMARY: Lung cancer is the second most common cancer entity and the leading cause of cancer-related deaths worldwide despite constant advantages in immune-oncology and personalized medicine. Invasion of the lymphatic and vascular system has been investigated as a risk factor in the past and available data suggested a strong prognostic impact. However, many studies did not distinguish between the invasion of the lymphatic and the vascular system. Furthermore, this issue has not yet been studied in a homogenous cohort treated by a VATS lobectomy and staged by the most recent 8th edition of the TNM staging. We hence examined the role of lymphatic and vascular invasion as two separate risk factors in NSCLC patients treated by a modern minimal-invasive VATS lobectomy to re-encourage the scientific interest in the prognostic role of vascular invasion and to further improve NSCLC risk stratification. ABSTRACT: Lung cancer is the most frequent cause of cancer-related death worldwide. The patient’s outcome depends on tumor size, lymph node involvement and metastatic spread at the time of diagnosis. The prognostic value of lymph and blood vessel invasion, however, is still insufficiently investigated. We retrospectively examined the invasion of lymph vessels and blood vessels separately as two possible prognostic factors in 160 patients who underwent a video-assisted thoracoscopic lobectomy for non-small-cell lung cancer at our institution between 2014 and 2019. Lymph vessel invasion was significantly associated with the UICC stage, lymph node involvement, tumor dedifferentiation, blood vessel invasion and recurrence. Blood vessel invasion tended to be negative prognostic, but missed the level of significance (p = 0.108). Lymph vessel invasion, on the other hand, proved to be a prognostic factor for both histological subtypes, adenocarcinoma (p < 0.001) as well as squamous cell carcinoma (p = 0.018). After multivariate analysis apart from the UICC stage, only lymph vessel invasion remained independently prognostic (p = 0.018). Remarkably, we found analogue survival curve progressions of patients with stage I, with lymph vessel invasion, compared to stage II non-small-cell lung cancer. After further validation in prospective studies, lymph vessel invasion might be considered as an upstaging factor in resectable lung cancer. Especially in the early-stage of the disease, it might represent an additional risk factor to consider adjuvant therapy after surgical resection.