Neoadjuvant chemotherapy followed by surgery versus upfront surgery in non-metastatic non-small cell lung cancer: systematic review and meta-analysis of randomized controlled trials

BACKGROUND: The favorable effect of postoperative chemotherapy on long-term survival has been well acknowledged in non-small cell lung cancer (NSCLC), while the role of neoadjuvant chemotherapy (NAC) remains obscure. This meta-analysis enrolling high-quality randomized controlled trials (RCTs) aimed at comparing NAC followed by surgery with upfront surgery (US) in efficacy and safety among non-metastatic NSCLC patients. MATERIALS AND METHODS: Relevant literatures were searched systematically from MEDLINE, EMBASE, and the Cochrane Library. We also screened references of relevant publications and conference proceedings. Primary outcomes were overall survival (OS), disease free survival (DFS), 3-year and 5-year survival rates, mortality, and recurrence. Secondary outcomes included tumor-free (R0) resection rates, response rate, and postoperative complications. Subgroup analysis according to ethnicity was further conducted. RESULTS: A total of 11 eligible RCTs comparing NAC (n = 1624) with US (n = 1639) and published from 1998 to 2013 were included. Compared to US, NAC contributed to longer OS and DFS, higher 3-year and 5-year DFS rates, and lower incidences of total mortality, overall recurrence and metastasis, and tended to cause higher 5-year OS rates. NAC was associated with reduced risks in recurrence compared to US. Patients receiving NAC had lower surgery and resection rates, but higher R0 resection incidence among resected cases. NAC especially benefited occident patients. The overall NAC response rate was 52.1%, and NAC-related toxicity rate was 58.3%. CONCLUSION: NAC may provide better survival, reduced recurrence, and improved R0 resection rates among NSCLC patients who had surgery, especially in occident patients. Further studies are needed to clarify the ethnic differences.