59
6
Radiographic Staging of Lung Cancer:
Computed Tomography and Positron Emission Tomography
Frank C. Detterbeck
PET or invasive tests are not needed), or, con- versely, when staging by clinical evaluation and imaging studies are clearly not suffi ciently reliable.
Clinical staging, as offi cially defi ned, includes any and all staging information available before the initiation of treatment (pathological staging is available only after a resection). More specifi - cally, clinical staging includes the clinical evalu- ation (history and physical exam), imaging tests [e.g., computed tomography (CT) and PET], as well as any biopsies (e.g., mediastinoscopy, needle aspiration of nodes, etc.). Thus, clinical staging can be based on physical signs and symptoms, on radiographic studies, or on invasive procedures.
This chapter assumes that patients have had a clinical evaluation and focuses on the reliability of imaging tests, particularly the role of PET imaging. This in turn defi nes the need for inva- sive clinical staging tests (e.g., mediastinoscopy, needle aspiration of nodes, etc.), but a full discus- sion of the advantages and disadvantages of dif- ferent invasive clinical staging tests is beyond the scope of this chapter.
In this chapter it is assumed that patients with a known or suspected lung cancer have had a chest CT scan. Although the chest CT can itself be viewed as a staging tool, it is done in order to better characterize an abnormality on a chest radiograph (CXR). The chest CT provides a great deal of diagnostic information, and in general, the combination of the patient’s risk factors, pre- sentation, and the CT appearance usually allow a presumptive clinical diagnosis to be made with a high degree of accuracy. This chapter will focus The issue of how to preoperatively stage patients
with known or suspected lung cancer is complex, and remains confusing despite a large number of publications on the subject. Part of the confusion arises from the multiplicity of available tests, but more importantly from the fact that the question to be addressed varies in different patient groups.
There are different subgroups of patients, par- ticularly with respect to mediastinal staging. The patients considered in one study may not be the same as those in another study, and often argu- ments are made for a particular approach in some patients using data that is not applicable because it pertains to a different subgroup. Another major obscuring factor is the frequent difference in per- spective of authors and practicing clinicians. In general, papers addressing the value of a proce- dure have retrospectively included all patients who underwent the procedure, and not defi ned the characteristics of the patients. The clinician, on the other hand, is faced with a patient in whom he can defi ne clinical and radiographic charac- teristics, but then has trouble using the published literature to fi nd data that specifi cally applies to this type of patient.
In this chapter, the approach taken is that from the perspective of the clinician, by considering the patient characteristics fi rst, and then using what can be gleaned from the literature to guide us on how to further evaluate the patient. The focus of the chapter is on the role of positron emission tomography (PET) imaging. More spe- cifi cally, the question is posed whether situations can be defi ned in which the initial clinical staging is suffi ciently reliable (further confi rmation by
on the patients in whom a diagnosis of lung cancer is strongly suspected, and will not pertain to those thought more likely to have another disease process (e.g., sarcoidosis, pneumonia, etc.).
6.1. General Considerations
Positron emission tomography scanning has clearly been shown to be a useful tool in evaluat- ing patients with a wide variety of malignancies.
This is to a large extent because PET can distin- guish tissues based on differences in cellular metabolism, rather than primarily anatomical size as is true for CT and, to a large extent, also conventional magnetic resonance imaging (MRI).
The cost of PET scanning has decreased substan- tially, although it is still a more expensive test than CT. Furthermore, the availability of PET has become quite commonplace in the United States, although in many instances it involves a mobile PET scanner.
In many communities, it has become quite routine to obtain a PET scan in any patient sus- pected of having a lung cancer. This is often done by the family practitioner simply because it is thought to be indicated in patients with lung cancer, but without a clear defi nition of the ques- tions to be addressed by the test, or an under- standing of how the results are to be interpreted.
This practice is deplored. Although PET is clearly a dramatically useful test in many cases, and although the test itself is safe, it does come at a cost of healthcare dollars, and, most importantly, is associated with a risk of misinterpretation or misapplication that has great potential for harm in some patients.
Defi ning appropriate indications for PET scan- ning in patients with suspected lung cancer is often confusing because PET has four different uses. Although any one is suffi cient to justify a PET, it is best to have a clear understanding of what question is to be addressed primarily by the scan. The fi rst use of PET is to aid in making a presumptive diagnosis of the primary lesion.
This is of little use in patients in whom the prob- ability of lung cancer is very high based on the radiographic appearance and the clinical assess- ment (risk factors, presentation), because the PET
will likely not rule out lung cancer, and a positive PET result will not obviate the need for tissue for a histological or cytological diagnosis. PET for diagnosis is primarily useful in patients with a nodule that has an intermediate risk of lung cancer, provided it is greater than 1 cm in diam- eter.1 The role of PET for diagnosis will not be discussed further in this chapter because of the low utility in patients with a strong suspicion of cancer and because patients with a low or inter- mediate suspicion of cancer are not the focus of this chapter.
The second use of PET is for the detection of distant metastases in asymptomatic patients or those with more subtle symptoms.2 The third potential use of PET imaging is for confi rmation of the presence or absence of mediastinal involve- ment.2 These two uses of PET are central to the subject of this chapter and will be discussed in detail. The fourth use of PET is to guide thera- peutic interventions.3 This includes prognos- tication, radiotherapy treatment planning, and assessment of response to chemotherapy. Such indications for PET are beyond the scope of this chapter.
A caveat of PET imaging is in the interpreta- tion of the results. There is a widespread ten- dency to view PET as black and white (positive or negative) with nothing in between. The reality is that PET scans often show areas of indeterminate uptake. There is little doubt that the interpreta- tion of these areas of PET uptake is signifi cantly infl uenced by the clinical information and judg- ment, although there is no literature that quanti- fi es it. The PET radiologist that is interpreting the scan with only limited (sometimes incorrect) clinical information passed on by clerical staff is at a disadvantage. This is particularly true for mobile PET scans, where there is little opportu- nity for the cancer clinician to discuss the PET fi ndings with the radiologist in order to combine the clinical with the radiographic judgment to arrive at a correct interpretation. Furthermore, the quality of the PET images is also variable.
There is clear data that shows that interpretation of PET without a CT scan is inferior, and further- more that a dedicated PET/CT results in improved accuracy. Therefore, as PET scans are more widely available, the expertise of those reading the scans, the ability to correlate this with CT fi ndings and
clinical judgment, and the quality of the scans themselves have become much more variable.
The applicability of the published data may not apply to many settings because this data almost invariably involves dedicated PET experts inter- preting scans in an optimal setting.
6.2. Clinical Stage IV
The fi rst step in evaluating a patient who is strongly suspected to have a non-small cell lung cancer (NSCLC) is always to talk with the patient.
This is an important part of making a clinical diagnosis of lung cancer (based on risk factors for lung cancer and local symptoms such as cough or hemoptysis). A crucial factor in staging the patient is to assess whether there are any signs or symptoms of distant metastases. This includes both constitutional symptoms (fatigue, anorexia, weight loss) as well as organ-specifi c symptoms, particularly with regards to bone and brain metastases (pain, headache, etc.). It is clear that the physician must listen carefully and pay atten- tion to even subtle symptoms.4
Some patients will have quite obvious signs of distant metastases (severe localized bone pain, focal neurological fi ndings, palpable metastases).
In this case, a PET scan is rarely justifi ed. In general, the presence of distant metastases can be confi rmed by a directed test that is much less expensive and can usually be done that same day. Examples are a brain MRI or CT in the patient with focal neurological fi ndings, a plain fi lm of a site of signifi cant bone pain, or a needle aspiration of palpable supraclavicular nodes or subcutaneous metastasis. Similarly, if the patient has a signifi cant pleural effusion, thoracentesis and cytology is the next appropriate step because palliative chemotherapy is the treatment for patients with a malignant pleural effusion regard- less of whether other metastases are demon- strated as well. If the directed test shows typical fi ndings (osteolytic bone lesions, brain meta- stases) in a patient with marked typical symp- toms, the diagnosis of stage IV disease can be made with confi dence without more extensive testing.5
Patients with more subtle symptoms of possi- ble distant metastases should clearly undergo
confi rmatory imaging.5 Although the sensitivity of a carefully done clinical evaluation for distant metastases is high, additional confi rmation is needed because of a false-positive rate of approx- imately 70%.5 Positron emission tomography is ideal because it is more likely to fi nd distant metastases than other imaging studies.6,7 (A brain MRI or CT should also be done because of PET limitations in detecting brain metastases.) Several studies have shown that in a direct comparison, PET scanning is more sensitive and specifi c than bone scanning.8,9 Hence, PET imaging should be preferred, and there is no justifi cation for obtain- ing a bone scan if a PET has already been done.
A small but signifi cant subgroup of patients presents without signs and symptoms of distant metastases, but with a solitary suspicious lesion noted on the chest CT scan. This is usually either an enlarged adrenal gland or a second pulmo- nary lesion in another lobe. It must be borne in mind that benign lesions are frequent (adrenal adenomas occur in 3%–4%, hepatic cysts or ade- nomas in 2% of normal patients,5 and pulmonary nodules in 16% of patients with lung cancer, of which the vast majority are benign.10,11) Further- more, patients with a satellite focus of cancer in the same lobe have an good prognosis, and should undergo evaluation and treatment without further investigation of the satellite nodule.12 Thus, in many cases further testing is not neces- sary if the lesion is typical of a normal benign fi nding. In those patients in whom a signifi cant suspicion of a metastasis exists, a PET scan is generally very useful in sorting out how to approach these patients. Besides demonstration of the presence or absence of uptake in the suspi- cious lesion, PET is useful because most patients with a metastasis will have additional lesions noted on PET (including in mediastinal nodes).
Alternatively, if the suspicion is high enough, a biopsy of the lesion may be warranted instead of PET imaging, which cannot deliver a histological specimen.
Patients who have a solitary site of distant metastasis by PET scan should undergo biopsy confi rmation of metastatic disease.13,14 This is because a substantial number (10%–50%) of these presumed solitary metastases are in fact benign lesions.15–17 Finally, it must be remembered that occasionally patients with a solitary distant
metastasis and no nodal involvement should be considered for a curative approach with resection of the primary and the metastasis.12
6.3. Clinical Stage III
The patients addressed in this section have enlarged mediastinal nodes on a chest CT scan, but are asymptomatic with regards to either con- stitutional or organ-specifi c symptoms (i.e., the defi nition of clinical stage III). The questions to be addressed are how reliable the negative clini- cal evaluation is with regards to distant meta- stases, and how reliable the CT appearance of mediastinal node involvement is. It should be noted that the CT criteria for a suspiciously enlarged mediastinal node is a node that is greater than 1cm in the short axis dimension on a trans- verse CT image.
There is consistent data from multiple sources indicating that asymptomatic clinical stage III patients should undergo further testing to iden- tify possible distant metastases.2 The false- negative rate of the clinical evaluation in these patients is about 15% to 30%.5 Several studies have confi rmed that PET will detect distant metastases in 25% to 30% of stage cIII patients.7,18,19 It has already been mentioned that PET is more sensitive than bone scan to detect bone metasta- ses; furthermore only a minority of the distant metastases found involve the bone.18 Hence, a very strong argument can be made for obtaining a PET scan to look for distant metastases in stage III patients (without a pleural effusion).
The role of either PET or invasive biopsy of mediastinal nodes is more confusing. This is in part because there are different groups of patients with potential mediastinal involvement and the reported data has not always described which groups were included in the analysis. The following paragraphs attempt to arrive at recom- mendations for each group because of the appli- cability to clinical care, realizing though that the data is often imperfect. It is assumed in the next paragraphs in this section that patients do undergo a PET scan (and brain MRI/CT) for the detection of distant metastases; furthermore it is assumed that no distant metastases were found.
Patients with known or suspected lung cancer without symptoms of distant metastases can be divided into four general groups on the basis of the chest CT characteristics (Figure 6.1). Group A has very extensive mediastinal infi ltration, to the point where discrete lymph nodes can no longer be discerned or measured, or where mediastinal structures (i.e., vessels, trachea, etc.) are encir- cled (infi ltrative stage cIIIa,b). Group B involves patients with discrete enlarged mediastinal lymph nodes by CT scan (nodal stage cIIIa or cIIIb). Groups C and D do not have radiographic mediastinal node involvement (by CT), and will therefore be discussed in the sections on clinical stage I and II.
In patients with stage cIII NSCLC with exten- sive mediastinal infi ltration (Group A, infi ltra- tive stage cIIIa,b), clinical experience suggests that this appearance on CT is quite reliable for malignant involvement.20 However, there is no data substantiating this because biopsies to confi rm malignancy have not been felt to be nec- essary. In these situations, PET scanning invari- ably demonstrates signifi cant uptake. Because the CT appearance alone is accepted as reliable without further biopsy, there is no reason to pursue a biopsy to confi rm PET uptake in the mediastinum either. (A biopsy may be necessary simply to confi rm the diagnosis and defi ne the cell type, but that is a different issue than obtain- ing a biopsy because the mediastinal staging is in question.)
Patients with enlargement of discrete medias- tinal nodes represent another group (group B, nodal stage cIIIa or cIIIb). In these patients it is well documented that reliance on the CT appear- ance alone is notoriously inaccurate because approximately 40% of patients do not have medi- astinal involvement.21 Again, such patients should undergo PET imaging to detect distant metasta- ses. However, the value of PET to defi ne the status of the mediastinal nodes is debatable because the data suggests that either a positive or a negative PET result in the mediastinum should be con- fi rmed by a tissue biopsy.2
It is generally agreed that positive PET uptake in the mediastinum should be confi rmed by biopsy20 because of a false-positive rate of 13% to 23%.21–24 Most clinicians would be uncomfortable relying on a negative PET scan in the face of
clearly enlarged mediastinal nodes, although data that pertains to this is limited. One study suggested the false-negative rate of PET in patients with enlarged mediastinal nodes was 8%,22 but a meta-analysis suggests that the prob- ability of N2,3 involvement after a negative PET scan is approximately 30%, given a pretest probability of 60% (for enlarged nodes by CT).24 Thus, in patients with enlarged mediastinal nodes tissue confi rmation should generally be obtained, regardless of the PET results. This can be accomplished either by a traditional medias- tinoscopy or by needle aspiration [using esopha- geal ultrasound, endobronchial ultrasound, or simple landmark-guided transbronchial aspira- tion (TBNA)].20 Each of these procedures has rea- sonably good sensitivity (with the lowest being for blind TBNA), but the false-negative rate of the needle aspiration techniques is 20% to 30%.20
6.4. Clinical Stage II
The role of PET imaging for distant staging in patients with a clinical stage II NSCLC is unclear.
Only one study has specifi cally reported on such patients (involving only 18 cII patients), and found that PET detected distant metastases in 18% of patients.18 Thus, PET can be justifi ed in these patients. Another approach is to argue that the data relating to CT scans in patients with cII NSCLC indicates that approximately 20% have mediastinal node involvement despite normal- sized nodes on CT.21 This approach argues that mediastinoscopy should be done fi rst; if it is posi- tive then a PET would be indicated to look for distant metastases, whereas if it is negative, then the PET could be omitted. However, it must be acknowledged that there is very little data to defi ne an evidence-based approach.
B
D A
C
FIGURE 6.1. Different categories of patients with regards to mediastinal staging by CT. (A) Group A, infiltrative stage cIIIa,b.
Patients with mediastinal infiltration of tumor, making individual lymph nodes impossible to distinguish. (B) Group B, nodal stage cIIIa or cIIIb. Patients with enlargement of discrete mediastinal
nodes. (C) Group C, stage cII or central stage cI. Patients with a central tumor or evidence of N1 nodal enlargement, but with a normal mediastinal CT. (D) Group D, peripheral stage I. Patients with a peripheral clinical stage I tumor and a normal mediastinal CT.
Similarly, the role of PET in staging of the mediastinum in patients with cII NSCLC is unclear. There is ample evidence of a 20% to 25%
chance of N2,3 nodal involvement despite normal- sized mediastinal nodes in these patients.21 This is true both for patients with enlarged N1 nodes as well as in patients with central tumors. These patients are classifi ed as Group C in Figure 6.1 (stage cII or central stage cI). In this group, PET uptake in a mediastinal node should be con- fi rmed, based on the 20% false-positive rate dis- cussed in the previous section. There is no data that directly defi nes the false-negative rate of PET in the mediastinum in these patients, although a false-negative rate of greater than 5% for PET can be estimated when the pretest probability of malignant involvement is 20% to 25%.24
In the absence of direct data for PET, one ratio- nal approach is to pursue invasive biopsy of the mediastinum in cII patients, given what is known from studies involving only CT imaging. In this example, the procedure of choice would be medi- astinoscopy rather that a needle aspiration tech- nique. This is due to the easier ability to sample multiple mediastinal nodes in the most promi- nent nodal areas, and due to the higher false- negative rate (20%–30%) for needle aspiration techniques, especially in normal-sized nodes.23 Another rational approach is to perform PET imaging in cII patients and omit mediastinos- copy if the PET is negative in the mediastinum (and for distant metastases). The advantage of the approach involving mediastinoscopy is that it is based on data that is directly derived from this group of patients, and also yields a tissue biopsy for diagnosis should there be mediastinal involvement.
6.5. Clinical Stage I
There is little role for PET in asymptomatic patients with a peripheral clinical stage I tumor.
If the clinical evaluation is negative, traditional staging tests (bone scan, brain CT, upper abdom- inal CT) detect distant metastases in less than 5% of patients.5 Positron emission tomography imaging also detects distant metastases in less than 5% of patients, as demonstrated by multiple studies (although some included a proportion of
cII patients or did not document a negative clini- cal evaluation).7,16,18,25,26 In fact, the chance of a false-positive PET fi nding is higher than the chance of identifying an actual metastasis, which underscores a danger of obtaining a PET scan in these patients.16 Thus, there is little justifi cation for PET to detect distant metastases in patients with clinical stage I tumors.
Similarly, the data does not strongly support the value of PET scanning to evaluate the medi- astinum in patients with peripheral cI tumors (Group D in Figure 6.1).2 The fact that thoracot- omy and node dissection discloses less than 10%
with positive mediastinal nodes argues against the use of PET for mediastinal staging in these patients.21 Less than 5% of 84 stage cI patients who underwent PET were found to have N2,3 node involvement in one study.26 Moreover, 60%
of the positive PET results in the mediastinum turned out to be false positives,26 underscoring the drawbacks of pursuing such imaging if the incidence of disease is low.
6.6. Summary
Table 6.1 is a general guideline regarding the need for PET imaging in patients with lung cancer. This algorithm assumes the patient has had a careful history and physical exam by a phy- sician experienced in dealing with lung cancer patients, and assumes the patient has had a chest CT scan. This schema represents a rational approach based on the available evidence. It is recognized that no approach is 100% accurate.
There must be a balance between the risk of sub- jecting a patient to futile resection (by miss- ing unsuspected metastases) versus denying the patient a curative approach (because of presumed metastases that are not truly present). Further- more, the process of staging requires judgment about the incremental benefi t versus the risks of further testing (morbidity and potential detri- ment by misleading results).
The text of this chapter provides a numerical assessment of the reliability of particular assess- ments (false-positive and false-negative rates), so that the clinician can weigh the pros and cons of adding another layer of testing in a particular patient. This weighing of pros and cons is the
process of clinical judgment and represents the art of medicine. Table 6.1 does not allow all these nuances to be represented, and inherently involves judgments about what degree of accu- racy is acceptable. In general terms, a less than 5% chance of changing the stage is considered acceptable in avoiding another imaging test, and a less than 10% chance acceptable for avoiding an invasive test.
In patients with very obvious signs of meta- static disease, there is little role for PET imaging, and a directed radiographic study or biopsy is usually more expedient and suffi cient. Patients with subtle signs of possible distant metastases need to be investigated more carefully, and PET represents an ideal test in this situation (as well as a brain MRI; level of evidence 1+; recom- mendation grade B). Furthermore, PET imag- ing is frequently useful in patients in whom a possible metastasis has been detected by the chest CT. In any of these scenarios, if PET imaging shows multiple areas of uptake that are typical for metastases, this is suffi cient; however, a solitary site of possible metastasis by PET or an atypical radiographic appearance or clinical presentation requires a biopsy of the site in question (level of evidence 2+; recommendation grade D).
Asymptomatic patient with radiographic stage cIII tumors (by CT) should undergo a PET and brain MRI/CT because there is a 25% to 30%
chance of fi nding distant metastases (level of evi- dence 2+; recommendation grade C). Patients with discrete nodal enlargement on CT should undergo tissue confi rmation of these nodes regardless of the PET fi ndings (level of evidence 2++; recommendation grade B).
TABLE 6.1. Overview of recommended staging tests in patients with NSCLC.
Clinical scenario Next step Justification
cIV
Strong clinical symptoms Directed radiographic study or biopsy Expediency
Subtle clinical symptoms PET, brain MRI/CT 70% FP rate of clinical evaluation
Specific radiographic issue (e.g., pulmonary PET, brain MRI/CT (vs. biopsy) Settle specific issue, rule in/out additional mets nodule, adrenal)
cIII (asymptomatic)
Mediastinal infiltration PET, brain MRI/CT 30% chance of distant metastases Discrete nodal enlargement PET, brain MRI/CT 25%–30% chance of distant metastases EUS-NA, TBNA (vs. Med) if no distant mets 20% FP, ~20% FN rate of PET in mediastinum cII (asymptomatic, normal mediastinum on CT)
Central tumor or cN1 on CT Mediastinoscopy 20% FN rate of CT in mediastinum, 30% FN rate of TBNA, EUS-NA; unclear value of PET for distant mets or mediastinal assessment PET, brain MRI/CT if Med + 20%–30% chance of distant metastases Resection if Med − <5% chance of distant metastases cI (asymptomatic, normal mediastinum on CT)
cI (peripheral lesion) Resection <5% chance of distant mets, <10% chance of
N2,3 mets
Abbreviations: CT, computed tomography; EUS-NA, esophageal ultrasound and needle aspiration; FN, false negative; FP, false positive; Med, medias- tinoscopy; mets, metastases; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PET, positron emission tomography; TBNA, trans- bronchial needle aspiration.
In patients with obvious metastatic disease, there is little role for PET imaging; patients with subtle signs of possible distant metasta- ses need to be investigated more carefully, and PET represents and ideal test in this situation (level of evidence 1+; recommendation grade B).
A solitary site of possible metastasis by PET requires a biopsy of the site in question (level of evidence 2+; recommendation grade D).
Patients with stage cIII tumors (by CT) should undergo a PET (level of evidence 2+; recom- mendation grade C).
Patients with discrete nodal enlargement on CT should undergo tissue confi rmation of these nodes regardless of the PET fi ndings (level of evidence 2++; recommendation grade B).
Two different approaches to patients with central tumors or stage II lung cancer can be jus- tifi ed, in part because the data for this stage is limited. One strategy involves an initial medias- tinoscopy, and a PET scan is obtained only if it is positive (level of evidence 3; recommendation grade D). This is based on a high incidence of positive N2,3 involvement in normal-sized nodes, which may well not show up on PET (the data regarding the false-negative rate of PET in this situation is unclear). An alternative would be to do a PET scan fi rst, and perform mediastinos- copy only if it is positive in the mediastinum (level of evidence 3; recommendation grade D).
Neither a PET scan nor mediastinoscopy is rec- ommended for patients with peripheral stage I tumors (level of evidence 2+; recommendation grade C).
phy imaging in the diagnosis of pulmonary nodules or masses. Chest 2004;125:2294–2299.
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4. Guyatt GH, Cook DJ, Griffi th LE, et al. Surgeons’
assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Ann Thorac Surg 1999;68:309–315.
5. Detterbeck FC, Jones DR, Molina PL. Extratho- racic staging. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, eds. Diagnosis and Treatment of Lung Cancer: An Evidence-Based Guide for the Practicing Clinician. Philadelphia:
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6. Marom EM, McAdams HP, Erasmus JJ, et al.
Staging non-small cell lung cancer with whole- body PET. Radiology 1999;212:803–809.
7. Weder W, Schmid RA, Bruchhaus H, Hillinger S, von Schulthess GK, Steinert HC. Detection of extrathoracic metastases by positron emission tomography in lung cancer. Ann Thorac Surg 1998;66:886–893.
8. Bury T, Barreto A, Daenen F, Barthelemy N, Ghaye B, Rigo P. Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer. Eur J Nucl Med 1998;25:1244–1247.
9. Cheran SK, Herndon JE 2nd, Patz EF Jr. Compari- son of whole-body FDG-PET to bone scan for detection of bone metastases in patients with a new diagnosis of lung cancer. Lung Cancer 2004;44:317–325.
10. Keogan MT, Tung KT, Kaplan DK, Goldstraw PJ, Hansell DM. The signifi cance of pulmonary nodules detected on CT staging for lung cancer.
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Patients with central tumors or stage II lung cancer can undergo (1) an initial mediastinos- copy with a PET scan obtained only if it is positive; or (2) a PET scan fi rst with mediasti- noscopy only if the PET is positive in the mediastinum (level of evidence 3; recommen- dation grade D).
Neither a PET scan nor mediastinoscopy is recommended for patients with peripheral stage I tumors (level of evidence 2+; recom- mendation grade C).
These recommendations are as evidence-based as possible. However, little data exists for some clinical scenarios. Perhaps future studies will address this so that PET imaging as well as inva- sive testing can be used in a rational, logical manner, avoiding overuse and misinterpretation of results.
Acknowlegments. This work was performed at the Yale University.
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