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Originally published as JCO Early Release 10.1200/JCO.2005.04.7480 on March 27 2006 © 2006 American Society of Clinical Oncology.
New Horizons in Staging for Non–Small-Cell Lung CancerUniversity Hospital Zurich, Zurich, Switzerland To determine the most appropriate therapy in patients with non–small-cell lung cancer (NSCLC), accurate staging is mandatory. The primary goal of staging is to select patients who are likely to benefit from primary surgery or from a multimodality treatment. The optimal strategy for staging should be simple, accurate, noninvasive, and cost effective. Computed tomography (CT) scan of the chest has been considered as the standard modality to assess the intrathoracic spread of NSCLC and is part of the traditional work-up used for staging purpose.1 CT provides excellent morphologic information on the extent of disease, but has limited ability to differentiate between benign and malignant lesions in an organ or in lymph nodes.2 CT has also limited usefulness in the detection of chest wall and mediastinal invasion with a sensitivity and specificity ranging from 50% to 70%, which impairs the evaluation of the resectability of such tumors.3,4 Furthermore, several meta-analyses reported low sensitivities and specificities of CT in the assessment of mediastinal lymph-node involvement, ranging from 50% to 65% and from 65% to 85%, respectively.5,6 The search for metastatic disease is very important to avoid futile thoracotomies and requires a careful clinical evaluation since approximately 40% of the patients with newly diagnosed lung cancer present with symptoms as of advanced disease.7 International guidelines by the American Thoracic Society and the European Respiratory Society recommended no additional diagnostic testing in patients without abnormal clinical findings, because the likelihood of metastatic disease is very low in such patients.1 On the contrary, other staging practices consisted of a systematic search for distant metastases and included a CT scan of the abdomen, a bone scintigraphy, and a CT or a magnetic resonance imaging scan of the brain in each patient with potentially operable lung cancer. The introduction of positron-emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) has modified the diagnostic and the staging approach for patients with NSCLC. Several studies have demonstrated that PET is more accurate than CT for the diagnosis and staging of NSCLC and can reduce the rate of unnecessary thoracotomy in patients with potentially resectable disease.8-10 The additional information provided is primarily due to the high sensitivity of the technique in detecting small-volume disease with increased metabolic activity. Since commercial PET scanners provide nominal spatial resolution of 4.5 mm to 6.0 mm in the center of the axial field of view, even lesions that are < 1 cm in diameter can be detected on the basis of an increased uptake of FDG.2 In his meta-analysis including 3,438 patients, Toloza5 showed that PET is consistently more accurate than CT for detecting or excluding nodal disease, with a sensitivity and specificity of 85% and 91%, respectively. The high negative predictive value of PET in the assessment of mediastinal lymph-node metastases led to the avoidance of more invasive staging procedures, such as mediastinoscopy in most of the patients with PET-negative mediastinum, and eventually to reserve these other procedures for restaging if required.11 In the article published by Herder et al12 in this issue of the Journal of Clinical Oncology, the number of patients requiring at least one invasive procedure for mediastinal staging was significantly lower in patients who underwent early PET in comparison with patients who underwent the traditional work-up for diagnosis and staging of NSCLC. According to the assessment of the extension of the disease, previous studies demonstrated the high accuracy of whole-body PET in the detection of unsuspected extrathoracic metastases in up to 17% of patients.4,8,13 High sensitivity of PET has been shown in the detection of adrenal metastases and bone metastases, but not in the diagnosis of brain metastases. PET produces fewer false-positive results in degenerative, inflammatory, and post-traumatic bone disease compared with bone scintigraphy.14 The ability of PET imaging to stage both intra- and extrathoracic sites in one single examination with a better accuracy than conventional imaging has a potential impact on stage assignment and therapeutic decision making. The PET in Lung Cancer Staging (PLUS) trial and the American College of Surgeons Oncology group trial confirmed the role of PET to upstage up to 25% of the patients and to improve selection of surgically curable patients with NSCLC when added to the standard work-up.10,15,16 As a consequence, PET has become widely adopted as a major tool for the evaluation of patients with NSCLC and has been increasingly incorporated into the routine work-up. In their study, Herder et al12 evaluated if application of PET early in NSCLC diagnostic work-up reduces the number of tests required to stage the patients accurately in comparison with a traditional work-up. This randomized multicenter trial failed to show a reduction of the total of investigations needed for staging in the PET arm. There are several possible reasons to explain these results. The study design and the criteria used to analyze the data, to define a relapse, and to interpret the follow-up, may play an important role. Herder et al12 discuss the variable level of experience in the interpretation of PET imaging among the different institutions.
Patients with all of the stages of the disease were included in the study by Herder et al.12 The patients with early stage of NSCLC represented approximately one half of the patients included in each arm. However, the role of PET in the diagnosis and staging of small peripheral NSCLC is still unclear.17 A recent retrospective study by Port et al18 including 64 patients suggested that PET has no demonstrable benefit in the diagnosis, staging, or prognosis of patients with tumors of The main drawback of PET is the poor quality of its anatomic information. The limitations of PET to depict anatomic landmarks and its limited spatial resolution restrict its use for assessing tumor staging, regarding size of the lesion and potential infiltration of the chest wall and of the mediastinum.2,4 Tracing focal abnormalities to specific single lymph nodes is difficult or even impossible with the use of PET alone, which can make impossible the distinction between N1 and N2 disease. Moreover, the clinical significance of a single focal abnormality on PET remains often unclear, given that FDG accumulation is not specific for malignant tissue. Tissue such as myocardium, intestine, muscle, lymphatic tissue, and inflammatory lesions also show FDG accumulation.20 As a consequence, equivocal findings are not rare with PET and the stage assignment can be difficult. The limited spatial resolution yielded by PET because of a lack of anatomic information could be overcome by combining morphologic CT and metabolic PET data. By using only visual correlation between CT scans and PET scans, the precise location of lesions remained sometimes difficult to determine due to positional and motion-induced misregistrations, and several studies have demonstrated that this approach did not increase the accuracy of mediastinal staging over that obtained by PET alone.2,21 New imaging systems using integrated PET-CT have been developed.22 The results of several studies suggest that integrated PET-CT was superior to PET alone, CT alone, or visual correlation of PET with CT in determining the stage of disease in NSCLC.2,21 Significant improvements in tumor staging with therapeutic implications were found with integrated PET-CT.11 The anatomic correlation of the radionuclide uptake made possible a more precise delineation of the location of the primary tumor with improvement in the diagnosis of chest-wall infiltration and mediastinal invasion by the tumor.2,21,23 Integrated PET-CT permitted a small focal abnormality to be traced to a specific lesion and could potentially reduce the number of false-positive PET studies by correctly factoring in the physiologic variation in uptake in a specific organ or structure and reduce the number of futile thoracotomy by precisely assessing of distant metastases.2,21,23 In a prospective study including 350 patients staged by whole-body integrated PET-CT, solitary extrapulmonary lesions were found in 21% of patients.14 In half of these patients, lesions were not related to lung cancer but represented benign inflammatory lesions or other malignancies which would have been overlooked with conventional staging. The findings of whole-body integrated PET-CT imaging could clearly affect therapeutic management in patients with operable NSCLC.14,21,23 Due to its ability to correlate directly FDG-accumulating lesions with morphologic structures, integrated PET-CT may also have other potential advantages or indications. In the restaging after induction therapy, the correlation between the regression of FDG uptake after induction therapy and the pathologic examination may lead to a better comprehension of the biologic behavior of a tumor and of the prognosis.4 Integrated PET-CT can be used to delineate more accurately the areas of active tumor, which might have an impact on radiation therapy volume delineation in NSCLC. In a study including 26 patients with stages I through III NSCLC, Bradley et al24 found changes in radiation therapy planning in over 50% of patients after integrated PET-CT in comparison with CT targeting. In a study by Keidar et al, integrated PET-CT was demonstrated more effective than PET alone or visual correlation of PET and CT in the diagnosis of lung cancer recurrence.25 PET-CT changed the PET lesion classification in 52% of the patients by determining the precise localization of sites of increased FDG-uptake and changed the management of 29% of the patients.25 Based on the available data, integrated PET-CT provides a more precise staging than all the other imaging techniques, allowing a better selection of the patients for new modalities of therapy in the future. It is to expected that once integrated PET-CT becomes more widely available, it will be performed early in the diagnostic approach of selected patients with potentially resectable NSCLC and will become the preferred approach for determining the stage of disease in NSCLC. However, as mentioned by Herder et al,12 additional trials are required to define more precisely the groups of patients in which integrated PET-CT should be performed routinely and to evaluate if first-line integrated PET-CT is a cost-effective alternative in these patients. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. Author Contributions
REFERENCES
1. Official Statement of The American Thoracic Society and The European Respiratory Society: Pretreatment evaluation of non-small-cell lung cancer. Am J Respir Crit Care Med 156:320-332, 1997 2. Lardinois D, Weder W, Hany TF: Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348:2500-2507, 2003 3. 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 124:511-519, 2002 4. Vansteenkiste J, Fischer BM, Dooms C, et al: Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: Systematic review. Lancet Oncol 5:531-540, 2004[CrossRef][Medline] 5. Toloza EM, Harpole L, McCrory DC: Noninvasive staging of non-small cell lung cancer: A review of the current evidence. Chest 123:137S-146S, 2003 6. Birim O, Kappetein AP, Stijnen T, et al: Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in non small cell lung cancer. Ann Thorac Surg 79:375-381, 2005 7. Silvestri GA, Littenberg B, Colice GL: The clinical evaluation for detecting metastatic lung cancer: A meta-analysis. Am J Respir Crit Care Med 152:225-230, 1995[Abstract] 8. Kelly RF, Tran T, Holmstrom A, et al: Accuracy and cost-effectiveness of [18F]-2-fluoro-deoxy-D-glucose-positron emission tomography scan in potentially resectable non-small cell lung cancer. Chest 125:1413-1423, 2004 9. Lowe VJ, Fletcher JW, Gobar L, et al: Prospective evaluation of positron emission tomography in lung nodules. J Clin Oncol 16:1075-1081, 1998[Abstract] 10. Hoekstra CJ, Stroobandts SG, Hoekstra OS, et al: The value of [18F] fluoro-2-deoxy-D-glucose positron emission tomography in the selection of patients with stage IIIA-N2 non-small cell lung cancer for combined modality treatment. Lung Cancer 39:151-157, 2003[CrossRef][Medline] 11. Kerstine 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 73:394-402, 2002 12. Herder GJM, Kramer H, Hoekstra OS, et al: Traditional versus up-front [18F] fluorodeoxyglucose–positron emission tomography staging of non–small-cell lung cancer: A Dutch Cooperative randomized study. J Clin Oncol 24:1800-1806, 2006 13. Stroobants SG, D'Hoore I, Dooms C, et al: Additional value of whole-body fluorodeoxyglucose positron emission tomography in the detection of distant metastases of non-small-cell lung cancer. Clin Lung Cancer 4:242-247, 2003[Medline] 14. Lardinois D, Weder W, Roudas M, et al: Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer. J Clin Oncol 23:6846-6853, 2005 15. Red CE, Harpole DH, Posther KE, et al: Results of the American College of Surgeons Oncology Group Z0050 trial: The utility of positron emission tomography in staging potentially operable non-small cell lung cancer. J Thorac Cardiovasc Surg 126:1943-1951, 2003 16. Verboom P, van Tinteren H, Hoekstra OS, et al: Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: The PLUS study. Eur J Nucl Med Mol Imaging 30:1444-1449, 2003[CrossRef][Medline] 17. Viney RC, Boyer MJ, King MT, et al: Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 22:2357-2362, 2004 18. Port JL, Andrade RS, Levin MA, et al: Positron emission tomographic scanning in the diagnosis and staging of non-small cell lung cancer 2 cm in size or less. J Thorac Cardiovasc Surg 130:1611-1615, 2005 19. Wu J, Minato H, Tsunezuka Y, et al: Nodal occult metastasis in patients with peripheral lung adenocarcinoma of 2.0 cm or less in diameter. Ann Thorac Surg 71:1772-1778, 2001 20. Engel H, Steinert H, Buck A, et al: Whole-body PET: Physiological and artifactual fluorodeoxyglucose accumulations. J Nucl Med 37:441-446, 1996 21. Halpern BS, Schiepers C, Weber WA, et al: Presurgical staging of non-small cell lung cancer: Positron emission tomography, integrated positron emission tomography/CT, and software image fusion. Chest 128:2289-2297, 2005 22. Hany TF, Steinert HC, Goerres GW, et al: PET diagnostic accuracy: Improvement with in-line PET-CT system: Initial results. Radiology 225:575-581, 2002 23. Shim SS, Lee KS, Kim B, et al: Non-small cell lung cancer: Prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 236:1011-1019, 2005 24. Bradley J, Thorstad WL, Mutic S, et al: Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 59:4-5, 2004[CrossRef][Medline] 25. Keidar Z, Haim N, Guralnik L, et al: PET/CT using 18F-FDG in suspected lung cancer recurrence: Diagnostic value and impact on patient management. Nucl Med 45:1640-1646, 2004
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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2 cm. Furthermore, the use of PET in the evaluation of clinically suspicious, small, solitary, pulmonary lesions was associated with a high false-negative rate. In the series described by Port et al,
