PET with 18F-fluorodeoxyglucose for staging of non-small cell lung cancer

W. A. Weber; M. Dietlein; D. Hellwig; C.-M. Kirsch; H. Schicha; M. Schwaiger

doi:10.1055/s-0038-1625183

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2003; 42(04): 135-144
DOI: 10.1055/s-0038-1625183

Original Article

Schattauer GmbH

PET with ¹⁸F-fluorodeoxyglucose for staging of non-small cell lung cancer

Evidence-based recommendations and cost-effectivenessPET mit ¹⁸F-Fluordeoxyglukose in der Diagnostik des nicht kleinzelligen BronchialkarzinomsEvidenzbasierte Empfehlungen und Kosten/Nutzenabwägungen

Authors

W. A. Weber

¹Nuklearmedizinische Klinik und Poliklinik (Direktor: Prof. Dr. M. Schwaiger) der Technischen Universität München
M. Dietlein

²Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. H. Schicha) der Universität zu Köln
D. Hellwig

³Abteilung für Nuklearmedizin (Direktor: Prof. Dr. Dr. C.-M. Kirsch) der Radiologischen Universitätsklinik Homburg/Saar, Deutschland
C.-M. Kirsch

³Abteilung für Nuklearmedizin (Direktor: Prof. Dr. Dr. C.-M. Kirsch) der Radiologischen Universitätsklinik Homburg/Saar, Deutschland
H. Schicha

²Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. H. Schicha) der Universität zu Köln
M. Schwaiger

¹Nuklearmedizinische Klinik und Poliklinik (Direktor: Prof. Dr. M. Schwaiger) der Technischen Universität München

Abstract

Summary:

Aims: To evaluate studies on the use of positron emission tomography with the glucose analog ¹⁸F-fluorodeoxyglucose (FDG-PET) for the preoperative staging of patients with non-small cell lung cancer (NSCLC) according to the criteria of evidence based medicine and to discuss the cost-effectiveness of the technique. Methods: Clinical studies published between 1995 and 2002 on the preoperative staging of non-small cell lung cancer were used for this analysis. Studies that did not meet the criteria published by the European Agency for the Evaluation of Medicinal Products (EMEA) were excluded. The validity of the studies was evaluated by a standardized rating system developed by the Agency for Health Care Policy and Research (AHCPR). Results: For the detection of mediastinal lymph node metastases the mean sensitivity and specificity of FDG-PET on a patient basis is 85% and 87% (16 studies, 1355 patients). In studies that compared FDG-PET and computed tomography (CT) the mean sensitivity of CT was 66% at a specificity of 71%. In the detection of distant metastases FDG-PET correctly changed the tumor stage in 18% of the patients when compared to CT based staging (10 studies, 1073 patients). Five cost effectiveness analyses from the USA, Japan, and Germany concluded that FDG-PET improves the outcome of treatment at reduced or only slightly increased overall costs. Improvement of patient outcome was also demonstrated in a randomized trial, which found that the risk of a futile thoracotomy was reduced by 51% (p = 0.003) when FDG-PET was added to the preoperative staging. Conclusion: According to the criteria of the AHCPR the use of FDG-PET for detection of mediastinal lymph node and distant metastases is documented at a level of evidence Ia and Ib, respectively. Since systematic analyses also indicate a favorable cost-effectiveness ratio FDG-PET has to be considered as ”strictly indicated“ for the preoperative staging of non-small cell lung cancer.

Zusammenfassung:

Ziele: In dieser Arbeit wurde die Positronenemissionstomographie mit ¹⁸F-Fluordeoxyglukose (FDG-PET) zum präoperativen Staging des nicht kleinzelligen Bronchial-karzinoms (NSCLC) nach Kriterien der evidenzbasierten Medizin bewertet und Analysen zur Kosteneffektivität des Verfahrens diskutiert. Methodik: Von 1995 bis 2002 veröffentlichte Studien zur präoperativen NSCLCDiagnostik mittels FDG-PET wurden nach den Kriterien der European Agency for the Evaluation of Medicinal Products (EMEA) ausgewählt und nach einem standardisierten Rating-System der Agency for Health Care Policy and Research (AHCPR) bzgl. Validität ihrer Aussagen beurteilt. Ergebnisse: Die mittlere Sensitivität und Spezifität der FDG-PET beträgt auf Patientenbasis 85% bzw. 87% (16 Studien, 1355 Patienten). Für den direkten Vergleich mit der Computertomographie (CT) ergibt sich eine mittlere Sensitivität und Spezifität von 66% bzw. 71%. Beim Nachweis von Fernmetastasen führt die FDG-PET bei 18% der Patienten zu einer korrekten Veränderung des Tumorstadiums im Vergleich zur CT-basierten Diagnostik (10 Studien, 1073 Patienten). Fünf Kosten/Nutzenanalysen aus den USA, Japan und Deutschland kamen zu dem Schluss, dass FDG-PET das Behandlungsergebnis verbessern kann und zu reduzierten oder nur geringfügig erhöhten Gesamtkosten für Diagnostik und Therapie führt. Die Verbesserung des Behandlungsergebnisses wurde auch in einer randomisierten Studie belegt, in der das Risiko einer nicht kurativen Thorakotomie durch die FDG-PET um 51% verringert wurde (p = 0,003). Schlussfolgerung: Nach den AHCPR-Kriterien ist die Diagnostik von NSCLCLymphknoten- bzw. -Fernmetastasen auf Evidenzstufe Ia bzw. Ib belegt. Da außerdem eine günstige Kosten/ Nutzenrelation besteht, ist nach medizinischen und gesundheitsökonomischen Kriterien die FDG-PET zum präoperativen Staging des Bronchialkarzinoms als »streng empfohlen« anzusehen.

Key words:

EBM - NSCLC - staging - ¹⁸F-FDG-PET - cost-effectiveness analysis

Schlüsselwörter:

EbM - nicht kleinzelliges Bronchialkarzinom - Staging - ¹⁸F-FDG-PET - Kosten/Nutzenanalyse

Full Text

References

Literatur
1 Ausschuss_Krankenhaus.. Bekanntmachung der Verfahrensregeln zur Bewertung von Untersuchungs- und Behandlungsmethoden im Krankenhaus gemäß § 137 c SGB V. 2002.
2 Berlangieri SU, Scott AM, Knight SR. et al. F-18 fluorodeoxyglucose positron emission tomography in the non-invasive staging of non-small cell lung cancer. Eur J Cardiothorac Surg 1999; 16 (Suppl. 01) S25-30.
3 Boyer M, Viney R, Fulham M. et al. A Randomised Trial of Conventional Staging (CS) With or Without Positron Emission Tomography (PET) in Patients (Pts) with Stage 1 or 2. Non-Small Cell Lung Cancer (NSCLC), ASCO 2001: 1233.
4 Bury T, Dowlati A, Paulus P. et al. Whole-body ¹⁸FDG positron emission tomography in the staging of non- small cell lung cancer. Eur Respir J 1997; 10: 2529-34.
5 Changlai SP, Tsai SC, Chou MC. et al. Whole body ¹⁸F-2-deoxyglucose positron emission tomography to restage non-small cell lung cancer. Oncol Rep 2001; 8: 337-9.
6 Clancy C. Ensuring health care quality: an AHCPR perspective. Clin Ther 1997; 19: 1564-1571.
7 CPMP.. Points to consider on the evaluation of diagnostic agents. London: European Agency for the evaluation of medicinal products 2001
8 Dietlein M, Weber K, Gandjour A. et al. Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results. Eur J Nucl Med 2000; 27: 1598-609.
9 Dwamena BA, Sonnad SS, Angobaldo JO. et al. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s—meta-analytic comparison of PET and CT. Radiology 1999; 213: 530-6.
10 ECRI.. Positron emission tomography (PET) for the diagnosis and staging of non-small-cell lung cancer. part 1: results of ECRI’s meta-analyses. Health technology assessment information service. No 72 1998;
11 ECRI.. Positron emission tomography (PET) for the diagnosis and staging of non-small-cell lung cancer. part 2: cost-effectiveness analysis. Health technology assessment information service. No. 73 1998;
12 Eschmann SM, Friedel G, Paulsen F. et al. FDG PET for staging of advanced non-small cell lung cancer prior to neoadjuvant radio-chemo-therapy. Eur J Nucl Med Mol Imaging 2002; 29: 804-8.
13 Fischer BM, Mortensen J, Hojgaard L. Positron emission tomography in the diagnosis and staging of lung cancer: a systematic, quantitative review. Lancet Oncol 2001; 2: 659-66.
14 Gambhir SS, Hoh CK, Phelps ME. et al. Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med 1996; 37: 1428-36.
15 Gupta NC, Graeber GM, Bishop HA. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small (<1 cm), intermediate (1 to 3 cm), and large (>3 cm) lymph node lesions. Chest 2000; 117: 773-8.
16 Gupta NC, Graeber GM, Rogers 2nd JS. et al. Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer. Ann Surg 1999; 229: 286-91.
17 Gupta NC, Tamim WJ, Graeber GG. et al. Mediastinal lymph node sampling following positron emission tomography with fluorodeoxyglucose imaging in lung cancer staging. Chest 2001; 120: 521-7.
18 Hellwig D, Ukena D, Paulsen F. et al. Metaanalyse zum Stellenwert der Positronen-Emissions-Tomographie mit F-18-Fluorodesoxyglukose (FDG-PET) bei Lungentumoren. Pneumologie 2001; 55: 367-77.
19 Kernstine KH, McLaughlin KA, Menda Y. et al. Can FDG-PET reduce the need for mediastinoscopy in potentially resectable nonsmall cell lung cancer?. Ann Thorac Surg 2002; 73: 394-401 discussion 401-2.
20 Kernstine KH, Stanford W, Mullan BF. et al. PET, CT, and MRI with Combidex for media-stinal staging in non-small cell lung carcinoma. Ann Thorac Surg 1999; 68: 1022-8.
21 Kiyono K, Sone S, Sakai F. et al. The number and size of normal mediastinal lymph nodes: A postmortem study. Ajr Am J Roentgenol 1988; 150: 771-776.
22 Kosuda S, Ichihara K, Watanabe M. et al. Decision-tree sensitivity analysis for cost-effectiveness of chest 2-fluoro-2-D-[(18)F]fluorodeoxyglucose positron emission tomography in patients with pulmonary nodules (non-small cell lung carcinoma) in Japan. Chest 2000; 117: 346-53.
23 Lauterbach K. Gesundheitsökonomie als Teil der Qualitätsverbesserung. in Lauterbach K, Schrappe M. (eds) Gesundheitsökonomie, Qualitätsmanagement und Evidence-based Medicine. Stuttgart: Schattauer; 2001
24 Lauterbach K, Schrappe M. Gesundheitsökonomie, Qualitätsmanagement und Evidence-based Medicine – Eine systematische Einführung. Stuttgart: Schattauer; 2001
25 Liewald F, Grosse S, Storck M. et al. How useful is positron emission tomography for lymph-node staging in non-small-cell lung cancer?. Thorac Cardiovasc Surg 2000; 48: 93-6.
26 Marom EM, McAdams HP, Erasmus JJ. et al. Staging non-small cell lung cancer with whole-body PET. Radiology 1999; 212: 803-9.
27 Mijnhout GS, Hooft L, van Tulder MW. et al. How to perform a comprehensive search for FDG-PET literature. Eur J Nucl Med 2000; 27: 91-7.
28 Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997; 111: 1710-7.
29 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: 254-61.
30 Poncelet AJ, Lonneux M, Coche E. et al. PETFDG scan enhances but does not replace pre-operative surgical staging in non-small cell lung carcinoma. Eur J Cardiothorac Surg 2001; 20: 468-74 discussion 474-5.
31 Sackett D, Haynes R. The architecture of diagnostic research. BMJ 2002; 324: 539-541.
32 Saunders CA, Dussek JE, O’Doherty MJ. et al. Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer. Ann Thorac Surg 1999; 67: 790-7.
33 Schiller JH. Current standards of care in small-cell and non-small-cell lung cancer. Oncology 2001; 61 (Suppl. 01) 3-13.
34 Scott WJ, Shepherd J, Gambhir SS. Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg 1998; 66: 1876-83 discussion 1883-5
35 Steinert HC, Hauser M, Allemann F. et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology 1997; 202: 441-6.
36 Valk PE, Pounds TR, Hopkins DM. et al. Staging non-small cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 1995; 60: 1573-81 discussion 1581-2
37 van Tinteren H, Hoekstra OS, Smit EF. et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet 2002; 359: 1388-93.
38 Vansteenkiste JF, Stroobants SG, De Leyn PR. et al. Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients. J Clin Oncol 1998; 16: 2142-9.
39 Vesselle H, Pugsley JM, Vallieres E. et al. The impact of fluorodeoxyglucose F 18 positron-emission tomography on the surgical staging of non-small cell lung cancer. J Thorac Cardiovasc Surg 2002; 124: 511-9.
40 von Haag DW, Follette DM, Roberts PF. et al. Advantages of positron emission tomography over computed tomography in mediastinal staging of non-small cell lung cancer. J Surg Res 2002; 103: 160-4.
41 Weder W, Schmid RA, Bruchhaus H. et al. Detection of extrathoracic metastases by positron emission tomography in lung cancer. Ann Thor-ac Surg 1998; 66: 886-92 discussion 892-3
42 Weng E, Tran L, Rege S. et al. Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer. Am J Clin Oncol 2000; 23: 47-52.