Randomized controlled trials of induction treatment and surgery versus combined chemotherapy and radiotherapy in stages IIIA-N2 NSCLC: a systematic review and meta-analysis

Background: The efficacy of induction treatment plus surgery for improving postoperative survival in patients with non-small-cell lung cancer (NSCLC) in stages IIIA-N2 is controversial, especially compared with the combined chemotherapy and radiotherapy. We therefore performed a systematic review and meta-analysis of the published phase III randomized clinical trials (RCTs) to quantitatively evaluate the survival benefit of preoperative induction treatment vs. combined chemoradiotherapy.

Methods: We systematically searched for trials that started after January, 1980. We excluded relevant studies using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards. Our primary endpoint, overall survival (OS), was defined as the time from randomisation until death (any cause). Secondary endpoint was progression free survival (PFS). PubMed, EMBASE and Cochrane library were used for the study search. All analyses were by intention to treat.

Results: Three studies (1,084 patients) were centrally selected and analyzed for the present meta-analysis. Combination of the three randomized controlled trials showed that there was no significant benefit of induction treatment plus surgery compared to combined chemoradiotherapy on 2-year OS [risk ratio (RR) =1.00; 95% CI, 0.85-1.17; P=0.98] and 4-year OS (RR =1.13; 95% CI, 0.85-1.51; P=0.39). However, from the subgroup analysis, it showed a significant PFS benefit (RR =1.78; 95% CI, 1.08-2.92; P=0.02) regarded chemoradiotherapy as preoperative induction treatment, compared with chemotherapy alone for induction treatment (PFS) (RR =1.05; 95% CI, 0.61-1.81; P=0.86).

Conclusions: There was no significant OS benefit of induction treatment plus surgery compared with combined chemoradiotherapy in patients with NSCLC (stages IIIA-pN2) at 2 and 4 years. However, we could conclude PFS could be improved when radiation therapy was added into preoperative induction treatment. Given the potential advantages of adding radiation preoperatively, clinicians should consider using this treatment strategy in the stage IIIA-N2 disease after fully assessment of the patients.