Early Stage Non–Small-Cell Lung Cancer: Surgical Implications of the New Adenocarcinoma Classification
Authors: Raymond U. Osarogiagbon, Ramon Rami-Porta
Journal: Journal of Thoracic Oncology (2013)

In Response: Cafarotti et al.1Cafarotti S Dutly A Cardillo G Granone P Early stage non-small-cell lung cancer: surgical implications of the new adenocarcinoma classification.J Thorac Oncol. 2013; 8: e45Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar raise several questions about the optimal surgical lymph node staging procedure in patients with relatively low-risk non–small-cell lung cancer, especially adenocarcinoma in situ and minimally invasive adenocarcinoma. Their departure point was a report in this journal, of poor correlation between surgical mediastinal lymph node examination claims and an audit of lymph nodes identified in the pathology report.2Osarogiagbon RU Allen JW Farooq A Wu JT Objective review of mediastinal lymph node examination in a lung cancer resection cohort.J Thorac Oncol. 2012; 7: 390-396Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar The roles of minimally invasive lung resection and sublobar resection are not addressed in the reference publication.2Osarogiagbon RU Allen JW Farooq A Wu JT Objective review of mediastinal lymph node examination in a lung cancer resection cohort.J Thorac Oncol. 2012; 7: 390-396Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar But neither the technique of resection (open, video-assisted, robotic-assisted), nor the extent of resection (wedge, segmental, lobar, or more extensive) alter the need for an oncologically sound operation with negative margins and proper nodal staging. Until the results of the ongoing North American (Cancer and Leukemia Group B 140503 [ClinicalTrials.gov #00499330]) and Japanese (Japan Clinical Oncology Group 0802/West Japan Oncology Group 4607L) trials of sublobar resection for small tumors with different percentages of ground-glass opacity are available, caution must be exercised when recommending sublobar resection even for ground-glass opacity lesions of 2 cm or less because local recurrence has been observed after a follow-up period of more than 5 years.3Nakao M Yoshida J Goto K et al.Long-term outcomes of 50 cases of limited-resection trial for pulmonary ground-glass opacity nodules.J Thorac Oncol. 2012; 7: 1563-1566Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar Because of its prognostic value and the limitations of clinical staging, proper pathologic staging of resected lung cancer is mandatory. The definition of proper has been debated. Accepted options range from (variously defined) systematic sampling to en-bloc systematic nodal dissection.4Lardinois D De Leyn P Van Schil P et al.ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2006; 30: 787-792Crossref PubMed Scopus (499) Google Scholar American College of Surgeons Oncology Group Z0030 compared a thorough systematic node sampling (stations 2R, 4R, 7, and 10R on the right; 5, 6, 7, and 10 L on the left) to a more extensive mediastinal lymph node dissection, and found no difference in survival.5Darling GE Allen MS Decker PA et al.Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial.J Thorac Cardiovasc Surg. 2011; 141: 662-670Abstract Full Text Full Text PDF PubMed Scopus (539) Google Scholar All patients in this study received a thorough systematic sampling procedure before randomization to cessation of further dissection, or completion of a more extensive dissection. This trial cannot be invoked in defence of any practice of less extensive dissection than noted above. The European Society for Thoracic Surgery accepts lobe-specific nodal dissection for peripheral T1 squamous tumors, but requires examination of at least three mediastinal nodal stations, including station 7.4Lardinois D De Leyn P Van Schil P et al.ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2006; 30: 787-792Crossref PubMed Scopus (499) Google Scholar Attempts to limit mediastinal lymph node examination to less than selective dissection have adopted a sentinel lymph node examination strategy.6Nomori H Iwatani K Kobayashi H Mori A Yoshioka S Omission of mediastinal lymph node dissection in lung cancer: its techniques and diagnostic procedures.Ann Thorac Cardiovasc Surg. 2006; 12: 83-88PubMed Google Scholar However, this has proven infeasible in clinical trials.7Liptay MJ D'amico TA Nwogu C Thoracic Surgery Subcommittee of the Cancer and Leukemia Group B et al.Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial.J Thorac Oncol. 2009; 4: 198-202Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar There are no prospective studies of a strategy of no mediastinal lymph node examination, even in adenocarcinoma in situ and minimally invasive adenocarcinoma. The reference report demonstrated the unreliability of terminology thrown about to label the mediastinal lymph node examination procedure. Three observers (the operating surgeon, an auditing surgeon and the pathologist in his final report) had poor concordance in identifying the procedure performed. Most concordant cases were those in which no lymph node examination had been performed. Low lymph node counts suggested a severe problem in the quality of the examinations performed overall. The authors suggested that the etiology of the problem was mainly in the operating room practice, but also entertained the possibility of problems in pathology examination practices because of greater concordance between the operating and auditing surgeons than between the surgeons and the pathologist.2Osarogiagbon RU Allen JW Farooq A Wu JT Objective review of mediastinal lymph node examination in a lung cancer resection cohort.J Thorac Oncol. 2012; 7: 390-396Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar The question of the optimal lymph node examination procedure for patients with ostensibly low risk of lymph node metastasis will increase in importance with adoption of computed tomography screening for lung cancer.8The National Lung Screening Trial Research Team Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6870) Google Scholar However, there is currently no compelling evidence to support a strategy of ignoring the surgical lymph node examination. Unexpected lymph node metastasis can be detected in sufficient proportions of low-risk patients; hence this practice cannot be recommended, even in the era of positron emission tomography scans. In fact, two recent publications indicate that intraoperative nodal assessment should not be spared even in subcentimeter9Zhou Q Suzuki K Anami Y Oh S Takamochi K Clinicopathologic features in resected subcentimeter lung cancer—status of lymph node metastases.Interact Cardiovasc Thorac Surg. 2010; 10: 53-57Crossref PubMed Scopus (34) Google Scholar and in clinical T1a peripheral carcinomas.10Matsumura Y Hishida T Yoshida J Aokage K Ishii G Nagai K Reasonable extent of lymph node dissection in intentional segmentectomy for small-sized peripheral non-small-cell lung cancer: from the clinicopathological findings of patients who underwent lobectomy with systematic lymph node dissection.J Thorac Oncol. 2012; 7: 1691-1697Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Molecular staging methods may someday enable us to identify patients at low risk for lymph node metastasis, in whom surgical lymph node examination would be superfluous. Some day, adjuvant therapy will become so effective that the presence of locoregional lymph node metastasis will lose its prognostic significance, as seems to have happened in breast cancer.11Giuliano AE Hunt KK Ballman KV et al.Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.JAMA. 2011; 305: 569-575Crossref PubMed Scopus (2246) Google Scholar We are not there yet. Although we will get there someday, the road to that destination is narrow, rocky, and uphill. It will take a tremendous amount of labor to identify truly independent molecular predictors, which must be prospectively validated in well-characterized groups of patients in whom the best current prognostic tool, the pTNM staging system, has been correctly applied.12Osarogiagbon RU Predicting survival of patients with resectable non-small cell lung cancer: beyond TNM.J Thorac Dis. 2012; 4: 214-216PubMed Google Scholar