Visceral Pleural Invasion as a Determinant of Surgical Strategy in Non-Small Cell Lung Cancer: A Multicenter Study.

BACKGROUND: Visceral pleural invasion (VPI) has traditionally been regarded as a negative prognostic indicator in non-small-cell lung cancer (NSCLC). However, with the increasing adoption of sublobar resection for small-sized NSCLC, the clinical significance of VPI is being fundamentally reassessed. Specifically, it remains uncertain whether VPI is indicative of tumor size or represents distinct metastatic behavior. METHODS: We conducted a retrospective comprehensive multicenter study involving 2464 patients with pathologically confirmed NSCLC ≤ 3 cm who underwent complete resection at three Japanese institutions. The prevalence, metastatic patterns, and prognostic impact of VPI were systematically evaluated, with particular focus on histological growth patterns. RESULTS: VPI was identified in 370 patients (15%). Notably, VPI-positive tumors demonstrated a doubled incidence of lymph node metastasis (31% vs. 15%, p < 0.001) and a distinct metastatic profile characterized by preferential hilar spread (#12, 16.9%) and an increased risk of skip N2 metastasis (4.0% vs. 2.0%). Five-year recurrence-free survival was significantly reduced in the VPI group (33.7% vs. 50.6%, respectively). Conversely, adenocarcinomas with lepidic characteristics demonstrated a minimal risk of VPI or nodal metastasis, with incidences of 2% and 1%, respectively. This finding highlights the heterogeneity in the biological aggressiveness of small-sized NSCLC. CONCLUSIONS: Our findings suggest that VPI is not merely a histopathological descriptor but also acts as a clinically significant indicator of aggressive metastatic behavior, potentially enhancing surgical and staging approaches beyond just considering tumor size. With the increasing adoption of sublobar resection for small-sized NSCLC, recognizing that VPI appears to be associated with predominant hilar involvement and an elevated risk of skip N2 metastasis may help refine decisions on the extent of lung and lymph node resection.