Poor prognosis of NSCLC located in lower lobe is partly mediated by lower frequency of EGFR mutations

Hyun Woo Lee,Young Sik Park,Sangshin Park,Chang-Hoon Lee

doi:10.1038/s41598-020-71996-7

Abstract

It is controversial whether a tumor located in the lower lobe is related with worse outcome of non-small cell lung cancer (NSCLC). This study aimed to clarify the prognostic role of primary tumor location in NSCLC. Patients newly diagnosed with NSCLC in a tertiary referral hospital from January 2011 to December 2014 were followed up for 5 years. Of the 2,289 NSCLC cases, 911 (39.8%) cases pertained to lower lobe cancers. Patients with lower lobe cancer showed a higher all-cause mortality rate than those with non-lower lobe cancer (48.6% vs. 40.3%, p < 0.001). Patients with lower lobe cancer had a lower proportion of adenocarcinoma histology and epidermal growth factor receptor (EGFR) mutations. Furthermore, compared to patients with non-lower lobe cancer, those with lower lobe cancer had a higher level of tumor markers (neuron-specific enolase and cytokeratin fragment 21-1). Mediation analysis revealed that the association between lower lobe cancer and higher all-cause mortality could be explained by an indirect pathway through EGFR mutations (percent mediated = 17.3%, p = 0.005). The sensitivity analysis for adenocarcinoma patients showed similar results (percent mediated = 18.8%, p = 0.021). Lower lobe cancer is associated with a higher all-cause mortality risk in patients with NSCLC, which is partly mediated by a lower proportion of EGFR mutations.

Highlights

Lung cancer is the second most commonly detected cancer and the most leading cause of cancer death in the world, incidence and mortality have been decreased in recent d ecades[1]
The patients with non-small cell lung cancer (NSCLC) located in the lower lobes had a higher all-cause mortality rate than those with non-lower lobe cancers (48.6% and 40.3% respectively, P < 0.001)
The patients with lower lobe cancer had a higher proportion of non-adenocarcinoma histology, a higher tumor marker level, and a lower proportion of epidermal growth factor receptor (EGFR) mutations, which were associated with an increased risk for 5-year all-cause mortality

Summary

Introduction

Lung cancer is the second most commonly detected cancer and the most leading cause of cancer death in the world, incidence and mortality have been decreased in recent d ecades[1]. The location of non-small cell lung cancer (NSCLC) is considered as an important factor in predicting treatment efficacy and clinical prognosis. Differences of histologic type[7,8] and epidermal growth factor receptor (EGFR) m utations[9] were found according to tumor location. It has not been clearly explained how tumor location relates to clinical prognosis. It is unclear whether lower lobe cancer is significantly associated with worse prognosis.

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Conclusion