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McLoud Staging of Lung Cancer Centennial Article Commentary A CENTURY OF MEDICAL IMAGING "A System for the Clinical Staging of Lung Cancer"--A Commentary Theresa C. McLoud1 McLoud TC Each month the American Journal of Roentgenology will republish online one of the 100 most-cited articles from its first century. A corresponding commentary in the print journal by a contemporary radiologist will provide a current perspective. For a full list of these articles, see page 3 of the January 2006 issue of the AJR or go to www.ajronline.org. Keywords: cancer, cardiopulmonary imaging, chest imaging, lung disease DOI:10.2214/AJR.05.1968 Received November 8, 2005; accepted without revision November 17, 2005. 1Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Founders 216, Fruit St., Boston, MA 02114. Address correspondence to T. C. McLoud. AJR 2006; 187:269270 0361803X/06/1872269 American Roentgen Ray Society his seminal article by Mountain et T al. [1] is the first description of the application of the TNM classification scheme to the clinical staging of lung cancer. This original study consisted of 2,155 proven cases of lung cancer. The staging was based on results of physical examination findings, radiographic studies, endoscopic studies, mediastinoscopy, and thoracentesis. More than 300 survival curves were plotted for various characteristics of the primary tumor, spread to the regional lymph nodes, and distant metastases in various combinations. Various TNM sets were then assigned to stage groups to indicate prognosis. The TNM system (which was already in place at the time of the article by Mountain et al. [1]) uses common language to provide a basis for categorizing extent of disease. This classification by Mountain et al. [1] meets several important clinical objectives by aiding the clinician in the planning of treatment and making a quantitative estimate of prognosis. It makes possible comparison of the results of different treatments. The TNM staging classification is applicable to nonsmall cell lung cancer (NSCLC) and has been in universal use since 1986. It was modified in 1997 to more accurately group patients with similar prognosis and treatment options and in particular to identify patients who would benefit from surgery [2]. Since the introduction of this classification, imaging has played an important role in the clinical staging of lung cancer. At the time of the original publication by Mountain et al. [1], only standard chest radiography and conventional tomography were available for chest imaging, and assessment of distant metastatic disease was generally limited to nuclear medicine studies such as bone scintigraphy. CT has now become the most important diagnostic imaging procedure for the regional staging of lung cancer [3]. Helical CT and MDCT systems with automated bolus injection of contrast material provide detailed images of both local tumor extent (the T factor) and nodal metastases (the N factor). The introduction of the American Thoracic Society CT map of nodal stations has permitted accurate CT localization of abnormal nodes [4]. However, CT has important limitations in staging of the primary tumor. Sensitivity and specificity for both chest wall involvement and mediastinal invasion can be less than 65% [58]. These are critical areas that may determine surgical versus nonsurgical management. In the 1990s, many studies compared CT findings with the gold standard of mediastinoscopy or surgery for staging of lymph node metastases. Those studies showed that, regardless of the threshold size of lymph node chosen, CT findings in isolation could not be taken as clear evidence of malignant nodal involvement. About 20% of all nodes deemed malignant based on CT criteria will be benign [3, 58]. CT, however, continues to play an important and necessary part in the evaluation of patients with lung cancer. MRI plays an important role in the evaluation and staging of superior sulcus (or Pancoast's) tumors. Direct multiplanar imaging and large differences in signal intensity between tumor and soft tissue allow better assessment of invasion into the root of the neck, chest wall, and vertebral bodies [6, 911]. Because of the limitations of CT and MRI, the search for a better noninvasive technique for staging of lung cancer has led to the application of 18F-FDG PET for imaging both the mediastinum for nodal disease and the remainder of the body for distant metastases. A meta-analysis has confirmed that PET is significantly more accurate than CT in the detection of nodal mediastinal metastases, with a sensitivity and specificity of 79% and 91%, respectively, for PET versus 60% and 77% for CT [12]. The development of fusion im- AJR:187, August 2006 269 McLoud aging with PET/CT has permitted more precise localization of lymphadenopathy, allowing accurate separation of N1 from N2 disease and N2 from N3 disease. PET is sufficiently sensitive that a patient with negative mediastinal PET results may proceed directly to surgical resection of the primary tumor without a staging mediastinoscopy [13]. PET has also been shown to be more sensitive than conventional imaging in the detection of extrathoracic metastases--except brain metastases because of the high glucose uptake of the normal brain [13]. One of the major benefits of PET is its ability to minimize unnecessary thoracotomies [14]. In conclusion, the TNM classification system for the staging of lung cancer has led to important advances in the determination of prognosis and treatment of patients with this disease. Imaging, particularly CT and PET, has become an important tool for the determination of the extent of disease and appropriate clinical staging. The original work by Mountain et al. [1] provided an important framework for the appropriate management of patients with lung cancer. References 1. Mountain CF, Carr DT, Anderson WAD. A system for the clinical staging of lung cancer. AJR 1974; 120:130138 2. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111:17101717 3. Spiro SG, Porter JC. State of the art. Lung cancer: where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med 2002; 166:11661196 4. Tisi GM, Friedman PH, Peters RM, et al. American Thoracic Society: Clinical staging of primary lung cancer. Am Rev Respir Dis 1983; 127:659664 5. Quint LE, Francis IR. Radiologic staging of lung cancer. J Thorac Imaging 1999; 14:235246 6. Webb WR, Gatsonis C, Zerhouni EA, et al. CT and MR imaging in staging nonsmall cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. Radiology 1991; 178:705713 7. Dales RE, Stark RM, Raman S. Computed tomography to stage lung cancer: approaching a controversy using meta-analysis. Am Rev Respir Dis 1990; 141:10961101 8. McLoud TC, Bourgouin PM, Greenberg RW, et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992; 182:319323 9. Shiotani S, Sugimura K, Sugihara M, et al. Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging. Radiat Med 2000; 18:283290 10. McLoud TC, Swenson SJ. Lung carcinoma. Clin Chest Med 1999; 20:697713 11. Heelan RT, Demas BE, Caravelli JF, et al. Superior sulcus tumors: CT and MR imaging. Radiology 1989; 170:637641 12. Dwamena BA Sonnad SS, Angobaldo JO, Wahl RL. Metastases from nonsmall cell lung cancer: mediastinal staging in the 1990s--meta-analytic comparison of PET and CT. Radiology 1999; 213:530536 13. Marom EM, McAdams HP, Erasmus JJ, et al. Staging nonsmall cell lung cancer with whole-body PET. Radiology 1999; 212:803809 14. van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected nonsmall cell lung cancer: the PLUS Multicentre Randomized Trial. Lancet 2002; 359:13881393 270 AJR:187, August 2006