Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification to Upgrade Extracapsular Extension of Tumor in Nodes From R0 to Incomplete Resection

Abstract

Introduction

The International Association for the Study of Lung Cancer (IASLC) proposed a revised R classification to upstage extracapsular extension (ECE) of tumor in nodes from R0 to R1. Nevertheless, evidence to confirm this proposal is insufficient.

Methods

The study included 4061 surgical patients with NSCLC. After reclassification by IASLC-R classification, overall survival (OS) was analyzed to compare patients with ECE with those with R0, R(un), and incomplete resection (R1 and R2). The recurrence pattern of ECE was evaluated to determine whether it correlated with incomplete resection.

Results

Among 1136 patients with N disease, those without ECE (n = 754, 67%) had a significantly better OS than those with ECE (n = 382, 33%) (p < 0.001). This negative prognostic significance was consistent across multiple subgroups. Multivariate analysis revealed that ECE was an independent prognostic risk factor (p < 0.001). When patients with ECE were separated from the IASLC-R1 group, their OS was significantly worse than that of IASLC-R(un) patients, but comparable to that of the remaining patients in the IASLC-R1 patients when analyzing all patients and patients with N disease. Moreover, patients with ECE had an increased risk of local recurrence in the mediastinum (p < 0.001), ipsilateral lung (p = 0.031), and malignant pleural effusion or nodes (p = 0.004) but not distant recurrence including contralateral or both lungs (p = 0.268), liver (p = 0.728), brain (p = 0.252), or bone (p = 0.322).

Conclusions

The prognosis of ECE patients is comparable with that of R1 patients. Moreover, their higher risk of local recurrence strongly suggests the presence of occult residual tumor cells in the surgical hemithoracic cavity. Therefore, upgrading ECE into incomplete resection is reasonable.