Factors associated with distant recurrence following R0 lobectomy for pN0 lung adenocarcinoma

Abstract

Objective: We investigated factors associated with distant recurrence, disease-free survival (DFS), and overall survival (OS) following R0 lobectomy for pathologic node-negative (pN0) lung adenocarcinoma.

Methods: We performed a retrospective analysis of a prospectively maintained database of patients with pT1-3N0M0 non-small cell lung cancer. Exclusion criteria included metachronous lung cancer, sublobar/incomplete resection, nonadenocarcinoma histology, and induction/adjuvant therapy. The primary outcome was distant recurrence; secondary outcomes were DFS and OS. Associations between variables and outcomes were assessed by Fine-Gray competing-risk regression for distant recurrence and Cox proportional hazard models for DFS and OS.

Results: Of 2392 patients identified with pT1-3N0M0 lung adenocarcinoma, 893 met the inclusion criteria. Median follow-up was 35.0 months (range, 0.1-202 months). Thirteen percent of patients developed recurrence (n = 115), of which 86% (n = 99) were distant. The 5-year cumulative incidence of distant recurrence was 14% (95% confidence interval [CI], 11%-17%). On multivariable analysis, pT2a (hazard ratio [HR], 2.84; 95% CI, 1.56-5.16; P = .001) and pT2b/3 (HR, 6.53; 95% CI, 3.17-13.5; P < .001) tumors were associated with distant recurrence. Recent surgery was associated with decreased distant recurrence (HR, 0.43; 95% CI, 0.20-0.91; P = .028), and lymphovascular invasion was strongly associated with distant recurrence (HR, 1.62; 95% CI, 1.00-2.63; P = .05). DFS was independently associated with pT stage (P < .001) and lymphovascular invasion (P = .004).

Conclusions: In patients undergoing R0 lobectomy with pN0 lung adenocarcinoma, pT stage and lymphovascular invasion were associated with distant recurrence and decreased DFS. These observations support the inclusion of these patients in future clinical trials investigating adjuvant targeted and immunotherapies.

Keywords: lobectomy; lung adenocarcinoma; lymphovascular invasion; pathologic tumor stage; recurrence.