Adjuvant chemotherapy for visceral pleural invasion in 3-4-cm non-small-cell lung cancer improves survival

Abstract

Objectives: Visceral pleural invasion (VPI) guidelines, for tumours ≤4 cm are ambiguous. Non-small-cell lung cancers (NSCLCs) 3 to ≤4 cm are assigned the T2a designation. Similarly, any tumours with VPI, smaller than 3 cm, are upstaged and also assigned the same T2a designation. We hypothesized that adjuvant chemotherapy would significantly improve 5-year survival for NSCLC ≤4 cm with VPI.

Methods: The National Cancer Database was queried from 2010 to 2016 for cases of NSCLC with clinical stage I disease, ≤4 cm, who subsequently underwent surgical resection. These stage I NSCLCs were stratified according to clinical tumour sizes (0 to ≤1, 1 to ≤2, 2 to ≤3 and 3 to ≤4 cm). This cohort was then divided into groups with and without VPI and further split based on the administration of adjuvant chemotherapy. Kaplan-Meier analysis was used to calculate 5-year overall survival (OS) for patients categorized by tumour size, VPI status, and receipt of adjuvant chemotherapy. Multivariable Cox regression adjusting for tumour size and VPI status was used to determine associations between use of adjuvant chemotherapy and OS.

Results: A total of 61 454 patients with NSCLC and clinical tumour sizes <4 cm were identified and grouped based on size along with VPI and adjuvant chemotherapy. The 5-year OS for combined tumour sizes without VPI was higher than for patients with VPI (66.2% vs 59.5%, P < 0.001). The OS for tumour size (0 to ≤1, 1 to ≤2, 2 to ≤3 and 3 to ≤4 cm) was lower for patients with VPI regardless of size (all P ≤ 0.010). When all tumour sizes were combined, patients with VPI who received adjuvant chemotherapy had an improved 5-year OS compared to patients without adjuvant chemotherapy (65.5% vs 58.8%, P < 0.001). When cohorts were created by tumour size, only VPI tumours 3 to ≤4 cm had a statistically significant increase in 5-year OS for patients receiving adjuvant chemotherapy (68.8% vs 49.9%, P < 0.001). On multivariable Cox regression for OS, adjuvant chemotherapy was associated with significantly longer 5-year OS in tumour size 3 to ≤4 (hazard ratio = 0.62, 95% confidence interval 0.46-0.83, P = 0.001).

Conclusions: VPI remains a poor prognostic factor in clinically node-negative, T2a or less, NSCLC patients. Guidelines recommend considering chemotherapy for high-risk T2aN0, margin-negative patients-including those patients with VPI. Based on the analysis, adjuvant chemotherapy should be considered specifically for 3 to ≤4 cm with VPI due to an observed 5-year OS advantage.

Keywords: Adjuvant chemotherapy; Non-small-cell lung cancer; Stage I; Surgery; Visceral pleural invasion.