Benefit of adjuvant chemotherapy for patients with stage IB non-small cell lung cancer: a systematic review and meta-analysis

Background: Adjuvant chemotherapy (ACT) is routinely the recommended treatment for patients with advanced non-small cell lung cancer (NSCLC) but remains a controversial option in stage IB patients. We therefore pooled the current evidence to determine the prognostic impact of ACT in stage IB NSCLC patients in the context of the eighth tumor, node, metastasis (TNM) staging system. Methods: Five electronic databases were searched for eligible studies up to December 2020 without language restrictions. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS). Search results were filtered by a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The risk of bias was assessed independently using a modified set. Stata 16.0 was used for general data analysis and meta-analysis, and subgroup analyses were performed to investigate the source of interstudy heterogeneity. Results: In all, 12 eligible studies were identified and 15,678 patients included. Our results demonstrated that ACT was associated with improved OS [n=11; hazard ratio (HR) =0.65; 95% confidence interval (CI): 0.60-0.70; P<0.001; I-2=33.4%, P=0.131] and DFS (n=9; HR =0.73; 95% CI: 0.63-0.83; P<0.001; I-2=66.7%, P=0.002) in stage IB NSCLC patients. Subgroup analysis by histology indicated that administration of ACT conferred more favorable survival to both stage IB squamous cell carcinoma (n=1; HR =0.56; 95% CI: 0.28-0.84; P<0.001) and adenocarcinoma (n=6; HR =0.59; 95% CI: 0.47-0.71; P<0.001; I-2=31.0%, P=0.203). Meanwhile, both platinumbased ACT (n=7; HR =0.62; 95% CI: 0.51-0.74; P<0.001; I-2=44.8%, P=0.093) and other regimens (n=2; HR =0.66; 95% CI: 0.61-0.72; P<0.001; I-2=0.7%, P=0.316) could benefit patients with stage IB disease. Discussion: ACT might provide survival benefits to patients with stage IB NSCLC irrespective of histology or regimens. Patient selection and time trend biases were inevitable due to the limitation of retrospective studies. More prospective studies should be initiated to investigate the optimal ACT regimens in different histologic types in stage IB NSCLC patients.