Prognostic significance of micropapillary pattern and risk factors in patients with resected stage I lung adenocarcinoma and possible benefit of adjuvant therapy: a real-world multicenter study

Micropapillary (MP) pattern has been identified as a negative prognostic factor in patients with lung adenocarcinoma, but it has not been recognized as a high-risk factor for patients with stage IB lung adenocarcinoma treated with adjuvant chemotherapy. This multicenter cohort study aimed to evaluate the prognostic value of histological subtypes for stage I lung adenocarcinoma and to determine the relative survival benefit of adjuvant chemotherapy for subgroups based on MP pattern. This retrospective study included 412 patients with stage I lung adenocarcinoma [according the eighth edition of the tumor-node-metastasis (TNM) classification] with MP pattern who underwent complete surgical resection between January 2010 and December 2019. Patients were classified into 3 groups based on the proportion of MP component (10% and 50% as the threshold): MP component >50% (n=8), 10-50% (n=273) and <10% (n=131). Among the 412 patients, the median age was 63 years, and 73.4% (113/154) patients with MP component ≥10% and 63.8% (51/80) of those with MP component <10% had epidermal growth factor receptor (EGFR) mutations. Patients with MP component >50% had a shorter overall survival (OS) compared with those with MP components of 10-50% [10-50% vs. >50%: hazard ratio (HR) =0.293, 95% confidence interval (CI): 0.083-1.027; P=0.052] or <10% (<10% vs. >50%: HR =0.214, 95% CI: 0.056-0.816; P=0.02). Notably, in the univariate analysis, the factors associated with a worse recurrence-free survival (RFS) were spread-through-air-space (STAS) status (HR =2.131, 95% CI: 1.104-4.112; P=0.02), male sex (HR =1.693, 95% CI: 1.048-2.735; P=0.03), smoking history (HR =1.817, 95% CI: 1.126-2.931; P=0.01), and tumor size >2 cm (HR =1.832, 95% CI: 1.138-2.949; P=0.01). MP component and risk factors might be considered critical features for patients with stage I lung adenocarcinomas and may inform the selection of patients who may benefit from adjuvant chemotherapy although no randomized evidence is available.