Outcome of surgery versus radiotherapy after induction treatment in patients with N2 disease: systematic review and meta-analysis of randomised trials

Abstract

Surgery should be considered as part of multimodality treatment for patients with resectable lung cancer and ipsilateral mediastinal nodal disease. In trials where patients received surgery as part of trimodality treatment, overall survival was better than chemoradiotherapy alone.

Management of Stage IIIA (N2) Non-Small Cell Lung Cancer: A Transatlantic Perspective

“…Furthermore, in trials of NSCLC with N2 disease, patients who underwent operations as part of a trimodality treatment had improved overall survival compared with those who received chemoradiotherapy alone. A recent metaanalysis and an editorial from Europe suggest that in patients with PET-CT-positive ipsilateral, nonbulky N2 disease, surgical staging of the mediastinum should be eliminated and upfront operations performed, followed by adjuvant chemotherapy [17,18]. There are no prospective trials to support this approach, and in the United States (where induction therapy is favored for any N2 disease) this may be challenging; nonetheless, this is an interesting and potential clinical trialprovoking observation.…”

Combined modality therapy in Stage IIIA non–small cell lung cancer: clarity or confusion despite the highest level of evidence?

“…[25]Induction CHT ± RT + surgery vs concurrent RT-CHT3RCT ( N  = 1,048)

2-year OS: HR 1.00; 95% CI 0.85–1.17; P  = 0.98

4-year OS: HR 1.13; 95% CI 0.85–1.51; P  = 0.39

3-year PFS: HR 1.05; 95% CI 0.61–1.81; P  = 0.86

No superiority of trimodality Tx over concurrent RT-CHT in both OS and PFS

McElnay et al . [26]Bimodality approach (CHT+surgery) vs concurrent RT-CHT4RCT ( N  = 229) (bimodality trials)HR 1.01; 95% CI 0.82–1.23; P  = 0.954No superiority of either bimodality or trimodality Tx over concurrent RT-CHTTrimodality approach (RT-CHT+surgery) vs concurrent RT-CHT2RCT ( N  = 820) (trimodality trials)HR 0.87; 95% CI 0.75–1.01; P  = 0.0686RCT ( N  = 1049) (all trials combined)HR 0.92; 95% CI 0.81–1.03; P  = 0.157Xu X-L et al . [27]Induction CHT ± RT + surgery vs concurrentRT-CHT5RCT only ( n  = 851)HR 0.94; 95% CI 0.81–1.09; P  = 0.686

No difference in OS in RCTs

OS superior with surgical approach in retrospective studies

Pooled studies suggest superiority in OS of surgical approach

No difference in PFS

Retrospective studies disproportionate weighting

4Retrospective only ( n  = 11 154)HR 0.58; 95% CI 0.46–0.71; P  = 0.0089Pooled studies ( n  = 12 005)HR 0.70; 95% CI 0.56–0.87; P  = 0.000Guo SX et al .…”

“…[26] identified six relevant trials [12–16, 18] and separated them into bimodality (CHT followed by surgery) and trimodality (RT-CHT followed by surgery) groups. The results of both bimodality and trimodality trials were the same: there was no statistically significant difference in OS when either of the two were compared with RT-CHT alone; this was also confirmed when the data of all studies were pooled.…”

“…Which is the most effective curative approach: induction CHT, with or without RT, followed by surgery, or RT-CHT alone?McElnay et al . [26] B. Which is the most effective curative approach: induction CHT, with or without RT, followed by surgery, or RT-CHT alone?Xu X-L et al .…”

Advances in the use of surgery and multimodality treatment for N2 non-small cell lung cancer

“…However as discussed above, the role of bimodality versus trimodality regimens is still not well established. In order to make more definitive recommendations a recent meta-analysis evaluated survival outcomes of patients with N2 disease in multimodality trials of chemotherapy, radiotherapy and surgery (31). Six trials with a total of 868 patients were included, 4 applying induction chemotherapy and 2 induction chemo-radiotherapy.…”