Oncological outcomes of unsuspected pN2 in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

Objectives: Optimal treatment of stage IIIA (N2) non-small-cell lung cancer (NSCLC) is controversial. Guidelines advise induction therapy before surgical resection. A proportion of patients with cN0 NSCLC are postoperatively upstaged due to unsuspected N2 disease. Survival of unsuspected N2 NSCLC treated with surgery varies and technical feasibility of video-assisted thoracic surgery (VATS) is unknown. The purpose of this study was to assess prevalence and survival of unsuspected N2 NSCLC treated with thoracotomy or VATS.

Methods: A systematic review and meta-analysis was performed of all available literatures through Pubmed, Cochrane, EMBASE, Web of Science, Trials registries and System for Information on Grey Literature (SIGLE) from 2000 to 2019. Outcomes of interest were prevalence, overall survival (OS) and disease-free survival of unsuspected N2 NSCLC. Secondary outcomes were number of harvested lymph nodes, postoperative complications and survival of unsuspected N2 NSCLC treated with VATS.

Results: Seventeen studies with patients with clinical stage N0-1 and unsuspected pN2 NSCLC were included. Prevalence of unsuspected pN2 was 8.6%. Three- and 5-year OS was 58% [95% confidence interval (CI) 37-78%) (N = 4337] and 35% (95% CI 28-43%) (N = 4337). Three- and 5-y ear disease-free survival was 48% (95% CI 30-66%) (N = 109) and 35% (95% CI 24-46%) (N = 517). VATS resulted in a low complication rate with similar 5-year OS as thoracotomy.

Conclusions: In patients with cN0-1 NSCLC, a minority has unsuspected pN2 NSCLC. Even for these patients, 5-year OS and disease-free survival are reasonable. VATS with adequate lymph node dissection is the treatment of choice when in experienced hands. Adjuvant therapy should be provided in absence of relevant comorbidity.