REVIEW
Mediastinal Staging in Lung Cancer. The quest for a cost-effective strategy
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1
Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA
2
Department of Pulmonary Medicine, 401 General Army Hospital, Athens, Greece
3
Department of Pulmonary Medicine, “Hygeia” General Hospital, Athens, Greece
Corresponding author
Vasileios S. Skouras
Department of Pulmonary and Sleep Medicine
401 General Army Hospital
1 Kanellopoulou Street, 11526, Athens, Greece
Pneumon 2014;27(1):52-67
KEYWORDS
ABSTRACT
Lung cancer is the most lethal cancer worldwide. The most favourable prognosis is achieved with complete resection of the malignant tumour, which is only feasible in the absence of both distant metastases and mediastinal involvement. The suitability for surgery in patients without metastases is therefore determined by accurate mediastinal staging. The methods available for this purpose include imaging and invasive techniques, but as no single method is sufficiently accurate at ruling in and ruling out mediastinal involvement in lung cancer a strategy based on the sequential use of staging methods is required. The cost-effectiveness of such a strategy depends on the sequence of the methods chosen and the requirement for further confirmation of the results of each method. The management of positive results derived from the various staging methods is well documented, but not the management of negative results, for which the current literature is not conclusive. The estimation by probability analysis of negative post-test probabilities following the use of the various methods can assist in the management of negative results and also provides guidance for future research related to the design of the most cost-effective strategy for staging mediastinal involvement in lung cancer.
ABBREVIATIONS
ACCP: American College of Chest Physicians,
AJCC: American Joint Committee on Cancer,
APW: aortopulmonary window,
CT: computed tomography,
DW-MRI: diffusion-weighted MRI,
EBUS-TBNA: endobronchial ultrasound TBNA,
EUS-NA: endoscopic ultrasound needle aspiration,
IASLC: International Association for the Study of Lung Cancer,
MLN: mediastinal lymph node,
MRI: magnetic resonance imaging,
n-PTP: negative post-test probability,
p-PTP: positive post-test probability,
PET: positron-emission tomography,
QALY: quality-adjusted life years,
STIR-SE-MRI: short-inversion time, inversion recovery, turbo spin-echo MRI,
SUVmax: maximum standard uptake value,
SVC: superior vena cava,
TBNA: transbronchial needle aspiration,
VAM: video-assisted mediastinoscopy,
VATS: video-assisted thoracoscopy
FUNDING
There was no funding for the present study .
REFERENCES (99)
1.
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2.
Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging Non-Small Cell Lung Cancer. Diagnosis and management of lung cancer: ACCP evidence-based clinical practice guidelines (3rd edition). Chest 2013;143:211-250.
3.
Minn AJ, Massague J. Invasion and Metastasis. In: DeVita VT, Lawrence TS, Rosenberg SA, (editors). DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology, 9th edn. Lippincott Williams & Wilkins, Philadelphia, PA, USA, 2011, pp. 113-27.
4.
Boffa DJ. The revised stage classification system for primary lung cancer. Clin Chest Med 2011;32:741-748.
5.
Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009;136:260-271.
6.
Albertine KH. Anatomy of the lungs. In: Mason RJ, Courtney Broaddus V, Martin TR, King Jr TE, Schraufnagel DE, Murray JF, et al., (editors). Murray and Nadel’s Textbook of Respiratory Medicine. Saunders (Elsevier Inc), Philadelphia, PA, USA, 2010, pp. 3-25.
7.
Robinson LA, Ruckdeschel JC, Wagner H, Jr., et al. Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl):243S-265S.
8.
Tournoy KG, Keller SM, Annema JT. Mediastinal staging of lung cancer: novel concepts. Lancet Oncol 2012;13:e221-229.
9.
Mountain CF, Carr DT, Anderson WA. A system for the clinical staging of lung cancer. Am J Roentgenol Radium Ther Nucl Med 1974;120:130-138.
10.
AJCC, UICC. AJCC cancer staging manual. Edge S, Byrd DR, Compton CC, editors. New York: Springer; 2009.
11.
Goldstraw P, Crowley J. The International Association for the Study of Lung Cancer International Staging Project on Lung Cancer. J Thorac Oncol 2006;1:281-286.
12.
(IASLC) IAftSoLC. Staging Manual in Thoracic Oncology. Goldstraw P, editor. Orange Park, FL, USA: Editorial Rx Press; 2009. 157 p.
13.
Dhillon SS, Dhillon JK, Yendamuri S. Mediastinal staging of non-small-cell lung cancer. Expert Rev Respir Med 2011;5:835- 850; quiz 51.
14.
Raptis CA, Bhalla S. The 7th Edition of the TNM staging system for lung cancer: what the radiologist needs to know. Radiol Clin North Am 2012;50:915-933.
15.
Detterbeck F, Puchalski J, Rubinowitz A, Cheng D. Classification of the thoroughness of mediastinal staging of lung cancer. Chest 2010;137:436-442.
16.
Lardinois 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;30:787-792.
17.
Silvestri GA, Jett JR. Clinical aspects of lung cancer. In: Mason RJ, Courtney Broaddus V, Martin TR, King Jr TE, Schraufnagel DE, Murray JF, et al., (editors). Murray and Nadel’s Textbook of Respiratory Medicine2010, pp. 1116-1144.
18.
Lepper PM, Ott SR, Hoppe H, et al. Superior vena cava syndrome in thoracic malignancies. Respir Care 2011;56:653-666.
19.
Koike T, Koike T, Yamato Y, et al. Predictive risk factors for mediastinal lymph node metastasis in clinical stage IA non-small-cell lung cancer patients. J Thorac Oncol 2012;7:1246-1251.
20.
Liu HB, Gu XL, Ma XQ, et al. Preoperative platelet count in predicting lymph node metastasis and prognosis in patients with non-small cell lung cancer. Neoplasma 2013;60:203-208.
21.
Wang JH, Zhang SC, Liu ZD, et al. [Correlation between the mRNA levels of carcinoembryonic antigen and cytokeratin 19 in peripheral blood with staging, treatment response and prognosis in patients with lung cancer]. Zhonghua Jie He He Hu Xi Za Zhi 2005;28:773-776.
22.
Shafazand S, Gould MK. A clinical prediction rule to estimate the probability of mediastinal metastasis in patients with non-small cell lung cancer. J Thorac Oncol 2006;1:953-959.
23.
De Leyn P, Vansteenkiste J, Cuypers P, et al. Role of cervical mediastinoscopy in staging of non-small cell lung cancer without enlarged mediastinal lymph nodes on CT scan. Eur J Cardiothorac Surg 1997;12:706-712.
24.
Wahl RL, Hutchins GD, Buchsbaum DJ, et al. 18F-2-deoxy2-fluoro-D-glucose uptake into human tumor xenografts. Feasibility studies for cancer imaging with positron-emission tomography. Cancer 1991;67:1544-1550.
25.
Paul NS, Ley S, Metser U. Optimal imaging protocols for lung cancer staging: CT, PET, MR imaging, and the role of imaging. Radiol Clin North Am 2012;50:935-949.
26.
Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;343:254-261.
27.
Duhaylongsod FG, Lowe VJ, Patz EF, Jr., et al. Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET). J Thorac Cardiovasc Surg 1995;110:130-139; discussion 9-40.
28.
Patz EF, Jr., Lowe VJ, Hoffman JM, et al. Focal pulmonary abnormalities: evaluation with F-18 fluorodeoxyglucose PET scanning. Radiology 1993;188:487-490.
29.
Hellwig D, Graeter TP, Ukena D, et al. 18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense? J Nucl Med 2007;48:1761-1766.
30.
Tournoy KG, Maddens S, Gosselin R, et al. Integrated FDG-PET/ CT does not make invasive staging of the intrathoracic lymph nodes in non-small cell lung cancer redundant: a prospective study. Thorax 2007;62:696-701.
31.
Cerfolio RJ, Bryant AS. Ratio of the maximum standardized uptake value on FDG-PET of the mediastinal (N2) lymph nodes to the primary tumor may be a universal predictor of nodal malignancy in patients with nonsmall-cell lung cancer. Ann Thorac Surg 2007;83:1826-1829; discussion 9-30.
32.
Lv YL, Yuan DM, Wang K, et al. Diagnostic performance of integrated positron emission tomography/computed tomography for mediastinal lymph node staging in non-small cell lung cancer: a bivariate systematic review and meta-analysis. J Thorac Oncol 2011;6:1350-1358.
33.
Wu Y, Li P, Zhang H, et al. Diagnostic value of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for the detection of metastases in non-small-cell lung cancer patients. Int J Cancer 2013;132:E37-47.
34.
Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 2003;139:879-892.
35.
Darling GE, Dickie AJ, Malthaner RA, et al. Invasive mediastinal staging of non-small-cell lung cancer: a clinical practice guideline. Curr Oncol 2011;18:e304-310.
36.
Hishida T, Yoshida J, Nishimura M, et al. Problems in the current diagnostic standards of clinical N1 non-small cell lung cancer. Thorax 2008;63:526-531.
37.
Watanabe S, Asamura H, Suzuki K, Tsuchiya R. Problems in diagnosis and surgical management of clinical N1 non-small cell lung cancer. Ann Thorac Surg 2005;79:1682-1685.
38.
Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg 2005;80:1207-1213; discussion 13-4.
39.
Darling GE, Maziak DE, Inculet RI, et al. Positron emission tomography-computed tomography compared with invasive mediastinal staging in non-small cell lung cancer: results of mediastinal staging in the early lung positron emission tomography trial. J Thorac Oncol 2011;6:1367-1372.
40.
Ravenel JG. Evidence-based imaging in lung cancer: a systematic review. J Thorac Imaging 2012;27:315-324.
41.
Herth FJ, Eberhardt R, Krasnik M, Ernst A. Endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes in the radiologically and positron emission tomographynormal mediastinum in patients with lung cancer. Chest 2008;133:887-891.
42.
Wang J, Welch K, Wang L, Kong FM. Negative predictive value of positron emission tomography and computed tomography for stage T1-2N0 non-small-cell lung cancer: a meta-analysis. Clin Lung Cancer 2012;13:81-89.
43.
Sommer G, Wiese M, Winter L, et al. Preoperative staging of non-small-cell lung cancer: comparison of whole-body diffusion-weighted magnetic resonance imaging and 18Ffluorodeoxyglucose-positron emission tomography/computed tomography. Eur Radiol 2012;22:2859-2867.
44.
Sieren JC, Ohno Y, Koyama H, et al. Recent technological and application developments in computed tomography and magnetic resonance imaging for improved pulmonary nodule detection and lung cancer staging. J Magn Reson Imaging 2010;32:1353-1369.
45.
Matsumoto Y, Kuroda M, Matsuya R, et al. In vitro experimental study of the relationship between the apparent diffusion coefficient and changes in cellularity and cell morphology. Oncol Rep 2009;22:641-648.
46.
Ohno Y, Koyama H, Nogami M, et al. STIR turbo SE MR imaging vs. coregistered FDG-PET/CT: quantitative and qualitative assessment of N-stage in non-small-cell lung cancer patients. J Magn Reson Imaging 2007;26:1071-1080.
47.
Yeh DW, Lee KS, Han J, et al. Mediastinal nodes in patients with non-small cell lung cancer: MRI findings with PET/CT and pathologic correlation. AJR Am J Roentgenol 2009;193:813- 821.
48.
Schieppati E. [Mediastinal puncture thru the tracheal carina]. Rev Asoc Med Argent 1949;63:497-499.
49.
Wang KP, Brower R, Haponik EF, Siegelman S. Flexible transbronchial needle aspiration for staging of bronchogenic carcinoma. Chest 1983;84:571-576.
50.
Epstein SK, Winslow CJ, Brecher SM, Faling LJ. Polymicrobial bacterial pericarditis after transbronchial needle aspiration. Case report with an investigation on the risk of bacterial contamination during fiberoptic bronchoscopy. Am Rev Respir Dis 1992;146:523-525.
51.
Herth FJF. Transbronchial needle aspiration and endobronchial ultrasound. In: Strausz J, Bolliger CT, (editors). Interventional Pulmonology. 48. European Respiratory Society Monograph, UK, 2010, pp. 317.
52.
Sherling BE. Complication with a transbronchial histology needle. Chest 1990;98:783-784.
53.
Witte MC, Opal SM, Gilbert JG, et al. Incidence of fever and bacteremia following transbronchial needle aspiration. Chest 1986;89:85-87.
54.
Holty JE, Kuschner WG, Gould MK. Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis. Thorax 2005;60:949-955.
55.
Harrow EM, Abi-Saleh W, Blum J, et al. The utility of transbronchial needle aspiration in the staging of bronchogenic carcinoma. Am J Respir Crit Care Med 2000;161(2 Pt 1):601-607.
56.
Schenk DA, Chambers SL, Derdak S, et al. Comparison of the Wang 19-gauge and 22-gauge needles in the mediastinal staging of lung cancer. Am Rev Respir Dis 1993;147:1251-1258.
57.
Chin R, Jr., McCain TW, Lucia MA, et al. Transbronchial needle aspiration in diagnosing and staging lung cancer: how many aspirates are needed? Am J Respir Crit Care Med 2002;166:377- 381.
58.
Davenport RD. Rapid on-site evaluation of transbronchial aspirates. Chest 1990;98:59-61.
59.
Diette GB, White P, Jr., Terry P, et al. Utility of on-site cytopathology assessment for bronchoscopic evaluation of lung masses and adenopathy. Chest 2000;117:1186-1190.
60.
Patelli M, Lazzari Agli L, Poletti V, et al. Role of fiberscopic transbronchial needle aspiration in the staging of N2 disease due to non-small cell lung cancer. Ann Thorac Surg 2002;73:407-411.
61.
Bernasconi M, Chhajed PN, Gambazzi F, et al. Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC. Eur Respir J 2006;27:889-894.
62.
Baram D, Garcia RB, Richman PS. Impact of rapid on-site cytologic evaluation during transbronchial needle aspiration. Chest 2005;128:869-875.
63.
Medford AR, Bennett JA, Free CM, Agrawal S. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA): applications in chest disease. Respirology 2010;15:71-79.
64.
Gu P, Zhao YZ, Jiang LY, et al. Endobronchial ultrasoundguided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer 2009;45:1389-1396.
65.
Herth FJ, Rabe KF, Gasparini S, Annema JT. Transbronchial and transoesophageal (ultrasound-guided) needle aspirations for the analysis of mediastinal lesions. Eur Respir J 2006;28:1264- 1275.
66.
Herth FJ, Eberhardt R. Actual role of endobronchial ultrasound (EBUS). Eur Radiol 2007;17:1806-1812.
67.
Eapen GA, Shah AM, Lei X, et al. Complications, consequences, and practice patterns of endobronchial ultrasound-guided transbronchial needle aspiration. Chest 2013;143:1044-1053.
68.
Yasufuku K, Nakajima T, Motoori K, et al. Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer. Chest 2006;130:710-718.
69.
Lee HS, Lee GK, Lee HS, et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal staging of non-small cell lung cancer: how many aspirations per target lymph node station? Chest 2008;134:368-374.
70.
Memoli JS, El-Bayoumi E, Pastis NJ, et al. Using endobronchial ultrasound features to predict lymph node metastasis in patients with lung cancer. Chest 2011;140:1550-1556.
71.
Trisolini R, Cancellieri A, Tinelli C, et al. Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial. Chest 2011;139:395- 401.
72.
Yarmus LB, Akulian J, Lechtzin N, et al. Comparison of 21-gauge and 22-gauge needle in endobronchial ultrasound-guided transbronchial needle aspiration. Results of the American College of Chest Physicians quality improvement registry, education, and evaluation registry. Chest 2013;143: 036-1043.
73.
Silvestri GA, Hoffman BJ, Bhutani MS, et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996;61:1441-1445; discussion 5-6.
74.
Micames CG, McCrory DC, Pavey DA, et al. Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging: A systematic review and metaanalysis. Chest 2007;131:539-548.
75.
Zhang R, Ying K, Shi L, et al. Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal lymph node staging of lung cancer: A meta-analysis. Eur J Cancer 2013.
76.
Wallace MB, Pascual JM, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA 2008;299:540-546.
77.
Gildea TR, Mazzone PJ, Karnak D, et al. Electromagnetic navigation diagnostic bronchoscopy: a prospective study. Am J Respir Crit Care Med 2006;174:982-989.
78.
Walker CM, Chung JH, Abbott GF, et al. Mediastinal lymph node staging: from noninvasive to surgical. AJR Am J Roentgenol 2012;199:W54-64.
79.
Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest 2012;142:385-393.
80.
Wlson DS, Bartlett RJ. Improved diagnostic yield of bronchoscopy in a community practice: combination of electromagnetic navigation sys- tem and rapid on-site evaluation. J Bronchol 2007;14:227-232.
81.
Kuzdzal J, Szlubowski A, Grochowski Z, Czajkowski W. Current evidence on transcervical mediastinal lymph nodes dissection. Eur J Cardiothorac Surg 2011;40:1470-1473.
83.
Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. BMJ 2004;329:168-169.
84.
Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA 2010;304:2245-2252.
85.
Farjah F, Flum DR, Ramsey SD, et al. Multi-modality mediastinal staging for lung cancer among medicare beneficiaries. J Thorac Oncol 2009;4:355-363.
86.
Gold MR. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996. xxiii, 425 p. p..
87.
Bleichrodt H, Quiggin J. Life-cycle preferences over consumption and health: when is cost-effectiveness analysis equivalent to cost-benefit analysis? J Health Econ 1999;18:681-708.
88.
Prieto L, Sacristan JA. Problems and solutions in calculating quality-adjusted life years (QALYs). Health Qual Life Outcomes 2003;1:80.
89.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727-1736.
90.
Sogaard R, Fischer BM, Mortensen J, et al. The optimality of different strategies for supplemental staging of non-small-cell lung cancer: a health economic decision analysis. Value Health 2013;16:57-65.
91.
Bugalho A, Ferreira D, Eberhardt R, et al. Diagnostic value of endobronchial and endoscopic ultrasound-guided fine needle aspiration for accessible lung cancer lesions after nondiagnostic conventional techniques: a prospective study. BMC Cancer 2013;13:130.
92.
Harewood GC, Pascual J, Raimondo M, et al. Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer. Lung Cancer 2010;67:366-371.
93.
Alzahouri K, Lejeune C, Woronoff-Lemsi MC, et al. Cost-effectiveness analysis of strategies introducing FDG-PET into the mediastinal staging of non-small-cell lung cancer from the French healthcare system perspective. Clin Radiol 2005;60:479- 492.
94.
Dietlein M, Weber K, Gandjour A, et al. Cost-effectiveness of FDG-PET for the management of potentially operable nonsmall cell lung cancer: priority for a PET-based strategy after nodal-negative CT results. Eur J Nucl Med 2000;27:1598-1609.
95.
Sharples LD, Jackson C, Wheaton E, et al. Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial. Health Technol Assess 2012;16:1-75, iii-iv.
96.
Medford AR, Agrawal S, Free CM, Bennett JA. A performance and theoretical cost analysis of endobronchial ultrasound-guided transbronchial needle aspiration in a UK tertiary respiratory centre. QJM 2009;102:859-864.
97.
Callister ME, Gill A, Allott W, Plant PK. Endobronchial ultrasound guided transbronchial needle aspiration of mediastinal lymph nodes for lung cancer staging: a projected cost analysis. Thorax 2008;63:384.
98.
Ang SY, Tan RW, Koh MS, Lim J. Economic analysis of endobronchial ultrasound (EBUS) as a tool in the diagnosis and staging of lung cancer in Singapore. Int J Technol Assess Health Care 2010;26:170-174.
99.
Farjah F, Lou F, Sima C, et al. A prediction model for pathologic n2 disease in lung cancer patients with a negative mediastinum by positron emission tomography. J Thorac Oncol 2013;8:1170- 1180.