Comment on “Treatment of Non-small Cell Lung Cancer Stage IIIA: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)”

Abstract

To the Editor: We read with concern the recent simple-article “ACCP Clinical Practice Guidelines for the Treatment of Stage IIIA (N2) Non-small Cell Lung Cancer” (NSCLC) [September 2007].1Robinson LA Ruckdeschel JC Wagner Jr, H et al.Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition).Chest. 2007; 132: 243S-265SAbstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar The authors concluded that “in patients with N2 disease identified preoperatively (IIIA3), platinum-based combination chemoradiotherapy is recommended as primary treatment.” We feel this recommendation is not supported by the available literature and ignores subsets of patients with stage N2 disease who should be considered for induction chemotherapy and surgical resection. Robinson et al1Robinson LA Ruckdeschel JC Wagner Jr, H et al.Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition).Chest. 2007; 132: 243S-265SAbstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar based their recommendations regarding the superiority of chemotherapy and radiation (C/RT) vs chemotherapy and surgery primarily on four purportedly “randomized, controlled” trials.1Robinson LA Ruckdeschel JC Wagner Jr, H et al.Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition).Chest. 2007; 132: 243S-265SAbstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar They erroneously included a study by Taylor et al,2Taylor NA Liao ZX Cox JD et al.Equivalent outcome of patients with clinical stage IIIA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection.Int J Radiat Oncol Biol Phys. 2004; 58: 204-212Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar which was a retrospective review of 107 patients with clinical stage N2 NSCLC, not a randomized trial. Additionally, the prematurely terminated Radiation Therapy Oncology Group (or RTOG) 89-01 trial3Johnstone DW Byhardt RW Ettinger D et al.Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2): final report of RTOG 89-01; Radiation Therapy Oncology Group.Int J Radiat Oncol Biol Phys. 2002; 54: 365-369Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar was underpowered, accruing only 27% of the target sample size. As the authors of that study pointed out, “patient accrual in this trial makes its results inconclusive.” Regarding the European Organisation for Research and Treatment of Cancer (or EORTC) trial,4van Meerbeeck JP Kramer GW Van Schil PE et al.Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.J Natl Cancer Inst. 2007; 99: 442-450Crossref PubMed Scopus (585) Google Scholar Robinson and colleagues1Robinson LA Ruckdeschel JC Wagner Jr, H et al.Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition).Chest. 2007; 132: 243S-265SAbstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar failed to mention that the study included only patients with unresectable stage N2 disease. Extrapolating the findings to patients with resectable stage N2 disease would seem inappropriate. Furthermore, the pneumonectomy rate in this study was high (55% of those undergoing resection), and only 50% of patients had complete tumor resection. Importantly, lobectomy resulted in no operative mortality and a 5-year survival rate of 27%, compared to only 13% for pneumonectomy and 14% for C/RT. In addition, local control was better with chemotherapy and surgery (68% vs 45%, respectively; significance not reported). Last, Intergroup trial 0139 showed a significantly better progression-free survival rate for induction chemoradiation/surgery compared to the definitive C/RT (22% vs 11%, respectively; p = 0.017), despite similar overall survival.5Albain KS Swann RS Rusch VR et al.Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA (pN2 non-small cell lung cancer: outcomes update of North American Intergroup 0139 (RTOG 9309) [abstract].J Clin Oncol. 2005; 23: 7014Crossref Google Scholar However, matching for age, gender, performance status, and T stage, patients who underwent lobectomy had a better overall survival rate than patients who were treated with definitive C/RT (36% vs 18% at 5 years, respectively; p = 0.002). This fact was overlooked in the review. As a multidisciplinary group, we disagree that the available data demonstrate the superiority of definitive C/RT over induction therapy plus surgery for all patients with stage IIIA/N2 NSCLC. Clearly, there are patients who are best treated with definitive C/RT, but there are also subsets of patients who may benefit from regimens that include surgery, such as patients with resectable tumors not requiring pneumonectomy, and those who are downstaged with induction therapy to stage ypN0 or ypN1. The current American College of Chest Physicians guidelines do not adequately address these favorable prognostic subgroups and oversimplify the management of what is a very heterogeneous NSCLC disease stage.