Journal of the National Cancer Institute Advance Access originally published online on July 24, 2007
JNCI Journal of the National Cancer Institute 2007 99(15):1210; doi:10.1093/jnci/djm051
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Re: Randomized Controlled Trial of Resection Versus Radiotherapy After Induction Chemotherapy in Stage IIIA-N2 Non–Small-Cell Lung Cancer
Affiliations of authors: Departments of Thoracic Surgery (FL, PS, GV, FP, LS), Oncology (TDP, G. Curigliano), and Radiotherapy (G. Catalano, GP), European Institute of Oncology, Milan, Italy; University of Milan School of Medicine, Milan, Italy (LS)
Correspondence to: Francesco Leo, MD, PhD, Department of Thoracic Surgery, European Institute of Oncology, Via Ripamonti, 435, Milan, 20141, Italy (e-mail: francesco.leo{at}ieo.it).
We read with interest the paper from van Meerbeeck et al. (1) on the final results of European Organisation for Research and Treatment of Cancer 08941 trial comparing radiotherapy and surgery in patients with N2 non–small-cell lung cancer after induction chemotherapy. They concluded that in selected patients who responded to chemotherapy, radiotherapy should be considered to be the preferred locoregional treatment.
We congratulate the authors for their excellent work. Nevertheless, there are some important considerations, given the impact of this publication. First, van Meerbeeck et al. cannot conclude that patients do not benefit from surgery because they did not select the right group. Patients with unresectable tumors are not good candidates for surgery, by definition. No information was given on the local extent of nodal disease, which means that bulky extracapsular N2 disease was not separated from limited N2 disease (the group that can really benefit from surgery). Extended nodal mediastinal involvement often means superior vena cava or tracheal carina involvement, and it can justify the high rate of exploratory thoracotomy of the study (14%), given that in these N2 patients surgery is not a reasonable option (2,3). This lack of selection can hide the possible advantage from surgery. To further confound the study conclusion, there is the problem of the sample size. Apart from the fact that the trial was closed after enrolling 50% of the planned population, the study hypothesis is not correct. The authors stated that the expected 5-year survival in the surgery arm was 25%. Survival ranging between 20% and 30% has been reported for patients "with various combinations of favorable features, such as complete resection, single-node or single-level involvement, microscopic or intracapsular metastasis, N2 confirmed to lower stations, and left upper lobe cancers with N2 limited to the subaortic level" (4). Thus, an expected survival rate of 25% can be obtained in patients only with truly resectable N2 disease, not in the whole group of patients with unresectable disease. The indirect proof is that patients with complete resection reached a 27% 5-year survival (1) even in the study of van Meerbeeck et al.
The final consideration relates to standards and quality of surgery. Dr Van Schil is an outstanding surgeon, and his work in the field of thoracic oncology is well known (5). However, the idea that the quality of surgery is equivalent worldwide should be abandoned. It is currently not acceptable that a study on the surgical treatment of N2 disease that recruits patients from 41 different institutions does not specify rules of mediastinal staging, type, and extent of mediastinal lymph node dissection and completeness of resection, as smaller studies previously did (6). The surgeon performing the operation is the only judge of the radicality of the resection; it cannot be established retrospectively by reviewing surgical and pathology reports only. The quality criteria of the radiotherapy treatment were reviewed in 1999 (7). Why weren’t the surgery quality criteria also reviewed in the surgery arm?
REFERENCES
(1) van Meerbeeck J, Kramer GWPM, Van Schil PEY, Legrand C, Smit EF, Schramel F, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Institute (2007) 99:442–50.
(2) Regnard JF, Perrotin C, Giovannetti R, Schussler O, Petino A, Spaggiari L, et al. Resection for tumors with carinal involvement: technical aspects, results, and prognostic factors. Ann Thorac Surg (2005) 80:1841–6.
(3) Spaggiari L, Leo F, Veronesi G, Solli P, Galetta D, Tatani B, et al. Superior vena cava resection for lung and mediastinal malignancies: a single-center experience with 70 cases. Ann Thorac Surg (2007) 83:223–9.
(4) Ponn RB, LoCicero J, Daly BDT. Surgical treatment of non-small cell lung cancer. In: General thoracic surgery—Shields TW, LoCicero J, Ponn RB, Rusch VW, eds. (2005) 6th ed. Philadelphia (PA): Lippincott Williams & Wilkins. 1570.
(5) Lardinois D, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg (2006) 30:787–92.
(6) Sugarbaker DJ, Herndon J, Kohman LJ, Krasna MJ, Green MR. Results of Cancer and Leukemia Group B protocol 8935. A multiinstitutional phase II trimodality trial for stage IIIA (N2) non-small-cell lung cancer. J Thorac Cardiovasc Surg (1995) 109:473–85.
(7) Kramer GW, Legrand CL, Van Schil P, Uitterhoeve L, Smit EF, Schramel F, et al. Quality assurance of thoracic radiotherapy in EORTC 08941: a randomised trial of surgery versus thoracic radiotherapy in patients with stage IIIA non-small-cell lung cancer (NSCLC) after response to induction chemotherapy. Eur J Cancer (2006) 42:1391–8.[CrossRef][ISI][Medline]
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 442-450.
J Natl Cancer Inst 2007 99: 1210-1211.
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