The Impact of Visceral Pleural Invasion in Node-Negative Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

Abstract

Visceral pleural invasion (VPI) is considered an aggressive and invasive factor in non-small cell lung cancer (NSCLC). Recent studies found that depending on tumor size, VPI influences T stage, but there is no consensus on whether VPI is important in node-negative NSCLC. In addition, its role in stage IB NSCLC is still uncertain. In this meta-analysis, we assessed the role of VPI in node-negative NSCLC according to various tumor sizes and especially in stage IB disease. A systematic literature search of four databases (EBSCO, PubMed, Ovid, and Springer) was performed to find relevant articles. The primary end point was 5-year overall survival. Pooled ORs were calculated using control as a reference group, and significance was determined by the Z-test. Thirteen relevant studies in 27,171 patients were included in this study. The number of patients with VPI was 5,821 (21%). VPI was a significant adverse prognostic factor in patients with tumor size ≤ 3 cm (OR, 0.71; 95% CI, 0.64-0.79; P < .001), > 3 but ≤ 5 cm (OR, 0.69; 95% CI, 0.56-0.86; P < .001), and > 5 but ≤ 7 cm (OR, 0.70; 95% CI, 0.54-0.91; P = .007). A further comparison was made with stage IB NSCLC. Tumor size ≤ 3 cm with VPI was associated with a better survival than tumor size > 3 but ≤ 5 cm regardless of VPI (OR, 1.31; 95% CI, 1.19-1.45; P < .001). Exploratory analysis found no survival benefit between tumor size ≤ 3 cm with VPI and tumor size > 3 but ≤ 5 cm without VPI (OR, 1.16; 95% CI, 0.95-1.43; P = .15); however, the prognosis for tumor size > 3 but ≤ 5 cm with VPI was not as good as that for tumor size ≤ 3 cm with VPI. VPI together with tumor size has a synergistic effect on survival in node-negative NSCLC. Patients with stage IB NSCLC and larger tumor size with VPI might be considered for adjuvant chemotherapy after surgical resection and need careful preoperative evaluation and postoperative follow-up. Further randomized clinical trials to determine the impact of adjuvant chemotherapy in patients with stage IB NSCLC with VPI are warranted.