PubMed and the Cochrane Library were used to initiate the search of relevant papers. The search was performed in August 2013 and included the years 2000–2013. Search terms included non-small cell lung cancer, induction therapy, neoadjuvant chemotherapy, neoadjuvant radiation therapy, pulmonary resection, morbidity, mortality, and cancer free survival. The papers that were included were those in English in which there was a clear explanation of the procedure performed. Other inclusion criteria of papers were the stage of the cancer treated, perioperative morbidity and mortality and long-term survival. Review papers were also analyzed for appropriate cross-references of other articles.

Several studies have evaluated patients undergoing pneumonectomy after neoadjuvant therapy for non-small cell lung cancer. Key studies will be summarized in this section. Using the Lung Cancer Study Group data, the overall baseline mortality rate for pneumonectomy for lung cancer was identified to be 6.2 % [1].

Daly et al. from the Boston Medical Center evaluated their data from 30 patients who received 5,940 cGy of radiation and two concurrent cycles of etoposide and cisplatin [2]. The authors examined morbidity, mortality and survival in this patient population. Eighteen patients underwent right pneumonectomy and 12 underwent left pneumonectomy. Thirty four percent (10/29) of these patients had a complete pathologic response. Fifty percent (3/6) of the patients with N1 nodal disease were node negative after neoadjuvant therapy, and 5/11 patients with N2 disease were down staged. 13.3 % (4/30) died in the postoperative period. Of these four patients, one had undergone a right pneumonectomy and expired from aspiration, myocardial infarction and heart failure. Three patients died who underwent left pneumonectomy; one from pneumonia, one from bronchopleural fistula, and another from a massive pulmonary embolism. Morbidity included 16.7 % (5/30) (all five from pneumonia, three due to aspiration). Median survival was 22 months and 5-year survival was 38 % [2].

The Radiation Therapy Oncology Group (RTOG) led a phase III multi-centered intergroup trial in patients with N2 non-small cell lung cancer (Int 0139). Patients were randomized to either concurrent platin based chemotherapy plus radiation therapy (45 Gy) followed by surgery or chemotherapy with definitive radiotherapy and no surgery. Patients in both arms were offered two additional cycles of chemotherapy. In this study, 16 of the 54 patients who underwent pneumonectomy died (29.6 %), the vast majority of whom had a right pneumonectomy. In addition, 45 % of the patients who underwent pneumonectomy were found to have T0N0 disease at the time of surgery. While the overall survival for the two study groups was not significantly different, there was a significant difference in survival and time to recurrence favoring the surgery arm in those patients who did not undergo pneumonectomy. The authors hypothesized that trimodality treatment might be beneficial if a complete resection could be accomplished without pneumonectomy, especially on the right side [3].

Martin et al. from Memorial Sloan Kettering performed a retrospective evaluation of patients undergoing pulmonary resection after induction chemotherapy or chemo radiation [4]. Of the 470 patients undergoing pulmonary resection, 97 (20.6 %) underwent pneumonectomy and of these, 55 patients underwent a standard pneumonectomy, 1 an extrapleural resection, 38 an intrapericardial resection, 2 a combined extrapleural and intrapericardial operation, and 1 a completion pneumonectomy. The overall mortality for all patients was 3.8 % (18/470). Within the pneumonectomy group, overall mortality was 11.3 % (11/97). In-hospital and late mortality in this group were 6.2 and 5.1 % and all deaths were in the 46 patients who underwent a right pneumonectomy. The overall morbidity in the pneumonectomy group alone was 46.4 % (58.7 % for right pneumonectomy and 35.3 % for left pneumonectomy). Multivariate analysis found right pneumonectomy, increased blood loss, and low FEV to be significant predictors of higher morbidity [4].

D’Amato et al. reported their data from the University of Pittsburgh and Ottawa Hospital in Canada [5]. In a retrospective fashion, the group compared 247 patients who underwent pneumonectomy alone versus 68 patients who underwent induction chemotherapy followed by pneumonectomy. Of these 68 patients, 33 received neoadjuvant radiation with an average dose of 45.6 Gy. The overall operative mortality was 9.2 % (10.5 % for right and 7.0 % for left). There was no significant difference in the overall incidence of bronchopleural fistula/empyema, respiratory failure, pneumonia, or 30-day mortality with regards to the side of the pneumonectomy. When comparing the groups who underwent neoadjuvant therapy versus surgery alone, there was also no significant difference in the incidence of bronchopleural fistula/empyema, respiratory failure, pneumonia, or arrhythmia. However, 30-day mortality in the neoadjuvant group was 21 % versus 6.1 % in the surgery alone group. The incidence of bronchopleural fistula and empyema was higher in patients undergoing neoadjuvant therapy and right pneumonectomy compared to left pneumonectomy (16.2 % versus 0 %) [5].

Maurizi et al. compared bronchial and/or vascular sleeve resection with patients undergoing pneumonectomy [6]. All patients received three cycles of chemotherapy consisting of cisplatin-gemcitabine, carboplatin-vinorelbine, or cisplatin-paclitaxel. Patients who underwent radiotherapy were excluded from this study. Thirty nine patients underwent sleeve lobectomy and 39 patients underwent pneumonectomy (19 right and 20 left). Final pathologic stage in the sleeve resection group was stage I in 17 (46.3 %), stage II in ten (25.6 %), and stage III in eight (20.5 %) patients. Complete pathological response was observed in four (10.3 %) patients. Final pathologic stage in the pneumonectomy group was stage I in six (15.4 %), stage II in 15 (38.5 %), and stage III in 18 (46.1 %) patients. 79.5 % of the sleeve resection group had down staging and 53.8 % of the pneumonectomy group had down staging. The postoperative complication rate in the pneumonectomy group was 33.3 % (13) and in the sleeve resection group was 28.2 % (11). There was one patient death in the pneumonectomy group immediately postoperatively (2.6 %) and none in the sleeve resection group. There was no difference in recurrence rate. The 3 and 5 year survival were 68.3 ± 8 and 64.8 ± 8 % for the sleeve resection group and 59.5 ± 5 and 34.5 ± 8 % for the pneumonectomy group. This may have reflected a much greater percentage of Stage III tumors in the pneumonectomy group. It is important to note that right-sided pneumonectomy did not confer a significant difference in morbidity or mortality [6].