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(Radiology. 1999;212:56-60.)
© RSNA, 1999

Thoracic Imaging

Lung Cancer Staging and Management: Comparison of Contrast-enhanced and Nonenhanced Helical CT of the Thorax1

Edward F. Patz, Jr, MD, Jeremy J. Erasmus, MD, H. Page McAdams, MD, John E. Connolly, MD, Edith M. Marom, MD, Philip C. Goodman, MD, Richard A. Leder, MD, Mary T. Keogan, MD and James E. Herndon, PhD

1 From the Department of Radiology (E.F.P., J.J.E., H.P.M., J.E.C., E.M.M., P.C.G., R.A.L., M.T.K.) and Biometry Division, Community and Family Medicine (J.E.H.), Duke University Medical Center, Box 3808, Erwin Rd, Durham, NC 27710. Received May 20, 1998; revision requested June 18; final revision received September 2; accepted December 15. Address reprint requests to E.F.P. (e-mail: patz0002@mc.duke.edu).


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To determine whether contrast material–enhanced helical computed tomography (CT) of the thorax and upper abdomen changes the tumor stage and management compared with nonenhanced helical CT in patients with newly diagnosed lung cancer.

MATERIALS AND METHODS: During 15 months, any patient in whom lung cancer was strongly suspected or newly diagnosed and who was scheduled for thoracic CT was considered eligible for the study. All patients underwent nonenhanced thoracic helical CT from the lung apices through the adrenal glands and then contrast-enhanced thoracic helical CT from the lung apices through the entire liver. Each study was read independently, and the thoracic radiologic stage was determined. Tissue sampling was performed and the final pathologic stage assigned.

RESULTS: Ninety-six patients had a final pathologic diagnosis of lung cancer. There was agreement in stage between the nonenhanced and contrast-enhanced examinations in 92 of the 96 patients. In three patients, the tumor stage at nonenhanced CT increased at contrast-enhanced CT, from IA to IIA (n = 1), IIB to IV (n = 1), and IIIB to IV (n = 1). In one patient, the tumor stage decreased from IIIB to IIB. There was no substantial change in management of any patient.

CONCLUSION: The results suggest that contrast-enhanced thoracic CT through the liver for staging lung cancer rarely changes the tumor stage determined with nonenhanced CT through the adrenal glands and does not substantially influence management decisions.

Index terms: Computed tomography (CT), comparative studies, 60.12111, 60.12112, 60.12115, 76.12111, 76.12112, 76.12115, 86.12111, 86.12112, 86.12115 • Computed tomography (CT), helical, 60.12115, 76.12115, 86.12115 • Lung, CT, 60.12111, 60.12112, 60.12115 • Lung neoplasms, 60.321, 60.334, 60.3313, 60.3376, 60.3386 • Lung neoplasms, staging, 60.33


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Computed tomography (CT) is the standard imaging modality used to radiologically stage lung cancer (1–7). CT protocols vary between institutions because the optimal and most cost-effective imaging parameters have not been rigorously established (8). Some radiologists prefer contrast material–enhanced studies through the chest and liver, whereas others prefer nonenhanced CT from the apices of the lungs through the adrenal glands. The former protocol covers a larger anatomic region and may demonstrate abnormalities that might not be seen with nonenhanced CT. This protocol, however, is subject to extra time, expense, and potential complications of intravenous contrast material administration. Furthermore, it is not clear whether the additional information results in more accurate radiologic staging or changes the management of patients with newly diagnosed lung cancer. We performed this study to compare the radiologic stage determined with nonenhanced helical CT with that determined by using contrast-enhanced helical CT of the thorax and upper part of the abdomen to determine whether the latter protocol would result in alterations in clinical management.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
During a 15-month period, all patients who presented to the radiology department for CT evaluation of newly diagnosed lung cancer or with chest radiographic findings strongly suggestive of lung cancer were considered eligible. Ultimately, only those patients with a pathologically proved diagnosis of lung cancer were included in the final analysis.

CT was performed with a CT HiSpeed Advantage scanner (GE Medical Systems, Milwaukee, Wis). The standard procedure at our institution was to perform nonenhanced helical CT from the lung apices through the adrenal glands by using the following imaging parameters: section collimation, 10 mm; pitch, 1; and reconstruction interval, 10 mm. Subsequently, each patient underwent contrast-enhanced helical CT with intravenous administration of 150 mL of iopamidol (Isovue 300; Bracco Diagnostics, Princeton, NJ) at a rate of 3 mL/sec from the lung apices through the lung bases beginning 25 seconds after the start of contrast enhancement; the imaging parameters were identical to those used for nonenhanced CT. Imaging of the liver began 70 seconds after intravenous administration of contrast material with a section collimation of 7 mm, a pitch of 1, and a reconstruction interval of 7 mm (8). Helical CT scans through the thorax were obtained in one breath hold, and a second set of images was obtained through the liver (also in one breath hold).

The scans were obtained by using a standard soft-tissue algorithm (window width, 350 HU; level, 40 HU) and a retrospective lung algorithm (window width, 1,500 HU; level, -600 HU). In addition, liver windows (nonenhanced CT: width, 160 HU; level, 40–60 HU; contrast-enhanced CT: width, 160 HU; level, 90–100 HU) were used to evaluate the abdominal images.

The nonenhanced CT scans of the chest were interpreted independently by at least two experienced thoracic radiologists (E.F.P., J.J.E., H.P.M., J.E.C., E.M.M., P.C.G.), and the abdominal images were interpreted independently by at least two experienced thoracic and/or abdominal radiologists (E.F.P., J.J.E., J.E.C., E.M.M., P.C.G., R.A.L., M.T.K.). Then, a radiologic stage was assigned by each reviewer. The contrast-enhanced scans were similarly interpreted independently and also assigned a radiologic stage by each reviewer. In patients with non–small cell lung cancer, disease was staged according to the newly revised International Staging System (9), and the local size and extension, regional lymph nodes, and distant sites of metastases were evaluated. For this study, lymph nodes larger than 1 cm in the short axis were considered positive. In patients with small cell lung cancer, disease was staged according to the guidelines of the Veterans Administration Lung Cancer Study Group (10). This classification system separates patients into two groups: those who have limited disease (tumor confined within a single radiation therapy port) and those who have extensive disease with distant metastases or noncontiguous metastases to the contralateral lung. Discrepancies in stage between reviewers were resolved by consensus.

Patient management was suggested independently for each nonenhanced and contrast-enhanced examination. If there was agreement in the radiologic stage determined with the nonenhanced and enhanced CT study, then management was, by definition, identical. If there was disagreement in the radiologic stage between the nonenhanced and enhanced CT study, then management decisions were typically as follows: Patients with stage I–IIIB disease underwent bronchoscopy or mediastinoscopy for airway evaluation and lymph node sampling, whereas patients with findings suggestive of metastatic disease underwent sampling of distant sites.

Pathologic sampling by means of transthoracic needle aspiration, bronchoscopy, mediastinoscopy, thoracotomy, or a combination of these procedures was used to determine the pathologic stage. Exact binomial CIs were computed for measures of agreement.


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
One hundred twenty-two patients were eligible for the study. Fourteen patients had diagnoses other than lung cancer, including aspergillosis (n = 1); lymphoma (n = 1); hamartoma (n = 2); fibrosis (n = 1); nonspecific inflammatory process, granuloma, or both (n = 5); actinomycosis (n = 1); tuberculosis (n = 1); pulmonary infarct (n = 1); and sarcoidosis (n = 1). A tissue diagnosis was not obtained in 12 patients. The remaining 96 patients had lung cancer, and they composed the study group.

Non–Small Cell Lung Cancer
Eighty-four patients (60 men, 24 women; mean age, 64 years; age range, 30–85 years) had non–small cell lung cancer. Twenty-four (29%) patients had squamous cell carcinoma, 21 (25%) had adenocarcinoma, three (4%) had large cell carcinoma, and 36 (43%) had unspecified non–small cell lung cancer.

There was complete agreement in the thoracic radiologic stage determined with nonenhanced and contrast-enhanced CT in 80 (95%) of the 84 patients (95% CI: 0.88, 0.99). Twenty-one patients had stage I disease, four had stage II disease, 16 had stage IIIA disease, 18 had stage IIIB disease, and 21 had stage IV disease. In the patients with stage IV disease, the sites of metastases included the liver (n = 8), lungs (n = 6), bone (n = 4), and adrenal glands (n = 5). There was agreement between the radiologic and pathologic stage in 75 (94%) of these 80 patients and disagreement in five (6%) (Table). Patients with radiologic stage I–IIIA disease underwent biopsy of the primary lesion, bronchoscopy, or mediastinoscopy, and patients with stage IIIB–IV disease underwent mediastinoscopy, bronchoscopy, or biopsy of distant sites so a final pathologic stage could be determined. Because there was agreement in radiologic stage between the nonenhanced and contrast-enhanced CT study, by definition there was no change in management.


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  		Agreement between Pathologic Stage and Radiologic Stage before and after Contrast Material Administration
 
There was disagreement in thoracic radiologic stage between nonenhanced and contrast-enhanced CT in four (5%) of the 84 patients. In three patients, the radiologic stage based on findings at contrast-enhanced CT was higher than that determined with nonenhanced CT. In one patient, the disease stage increased from IA (N0) to IIA (N1, hilar nodes); at mediastinoscopy, this patient had N2 disease (and, thus, stage IIIA disease) and was treated with chemotherapy and radiation therapy. In one patient, the disease stage increased from IIB to IV (possible small liver metastases); brain metastases were seen at head CT, which enabled us to confirm stage IV disease. In one patient, the disease stage increased from IIIB to IV (possible small liver metastases); bone metastases were seen on a bone scan, and stage IV disease was diagnosed at pathologic examination. In one patient, the radiologic stage decreased from IIIB (N3, aortopulmonary window nodes) to IIB (N1, hilar nodes) (Fig 1). At mediastinoscopy, this patient had N2 disease (and, thus, stage IIIA disease at pathologic examination) and was not considered a candidate for resection. In none of the patients was treatment changed because of the additional information noted at contrast-enhanced CT. Agreement between the thoracic radiologic stage and pathologic stage in all 84 patients is shown in the Table.



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  		Figure 1a. CT scans obtained in a 76-year-old man with a 4-cm mass in the right upper lobe of the lung. (a) Nonenhanced axial CT scan demonstrates a 1.5-cm, aortopulmonary window (level 5) lymph node (arrow). (b) Contrast-enhanced axial CT scan obtained at approximately the same level as a demonstrates no substantial aortopulmonary window adenopathy. No abnormalities were seen on any of the adjacent images. This patient underwent mediastinoscopy and had a right paratracheal (level 4R) lymph node positive for metastatic disease; stage IIIA non–small cell lung cancer was diagnosed.

 


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  		Figure 1b. CT scans obtained in a 76-year-old man with a 4-cm mass in the right upper lobe of the lung. (a) Nonenhanced axial CT scan demonstrates a 1.5-cm, aortopulmonary window (level 5) lymph node (arrow). (b) Contrast-enhanced axial CT scan obtained at approximately the same level as a demonstrates no substantial aortopulmonary window adenopathy. No abnormalities were seen on any of the adjacent images. This patient underwent mediastinoscopy and had a right paratracheal (level 4R) lymph node positive for metastatic disease; stage IIIA non–small cell lung cancer was diagnosed.

 
Eleven (13%) of the 84 patients with non–small cell lung cancer had at least one small (<5-mm) low-attenuating lesion in the liver that was considered unlikely to represent metastasis and therefore clinically unimportant (11). Four patients had liver lesions detected on both studies, and seven patients had lesions detected only on the contrast-enhanced studies (Fig 2). In no cases did the use of contrast material enable a more accurate characterization of liver lesions.



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  		Figure 2a. CT scans in a 71-year-old woman with a lobular right hilar mass. (a) Nonenhanced axial CT scan through the liver was interpreted as normal. (b) Contrast-enhanced axial CT scan through the liver obtained at approximately the same level as a demonstrates a 4-mm-diameter, low-attenuating lesion (arrowhead) that was too small to characterize any further. No abnormalities were seen on any of the adjacent scans. This patient underwent mediastinoscopy; N2 positive nodes and thus stage IIIA non–small cell lung cancer was diagnosed. The low-attenuating lesion in the liver was believed to be benign, and there were no changes in patient management.

 


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  		Figure 2b. CT scans in a 71-year-old woman with a lobular right hilar mass. (a) Nonenhanced axial CT scan through the liver was interpreted as normal. (b) Contrast-enhanced axial CT scan through the liver obtained at approximately the same level as a demonstrates a 4-mm-diameter, low-attenuating lesion (arrowhead) that was too small to characterize any further. No abnormalities were seen on any of the adjacent scans. This patient underwent mediastinoscopy; N2 positive nodes and thus stage IIIA non–small cell lung cancer was diagnosed. The low-attenuating lesion in the liver was believed to be benign, and there were no changes in patient management.

 
In six (six patients with bone metastases, two of which with both brain and bone metastases) of the 84 patients, extrathoracic metastases were demonstrated with additional radiologic studies performed preoperatively because of advanced disease or clinical symptoms. The thoracic radiologic stage in these patients before the discovery of metastatic disease was as follows: stage II (n = 1), stage IIIB (n = 1), and stage IV (n = 4).

Small Cell Lung Cancer
Twelve patients (seven men, five women; mean age, 64 years; age range, 47–80 years) had small cell lung cancer. There was complete agreement in the thoracic CT radiologic stage between the nonenhanced and contrast-enhanced studies in all cases. Seven patients had limited disease, and five had extensive disease.

In the patients with extensive disease, metastases were in the liver (n = 5) and bone (n = 2). One patient had additional liver lesions detected at contrast-enhanced CT, but this did not change the stage established at the nonenhanced examination. There was no change in pathologic stage or management decisions between the nonenhanced and enhanced studies in any case.


   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Lung cancer continues to be a major health problem. It is the most common malignancy in the United States and accounts for the greatest number of cancer-related deaths in both men and women (12). Unfortunately, because most patients have advanced disease at presentation, treatment options are limited to chemotherapy, radiation therapy, or both. Despite advances in these therapeutic regimens, the effect on the 5-year survival and disease-free interval has been minimal (12).

Many patients undergo extensive radiologic evaluation and laboratory studies to accurately define the clinical-radiologic stage before a final pathologic stage is determined with tissue sampling (1–7). Given the known patterns of metastases, imaging studies typically include thoracic CT through the adrenal glands and liver, radionuclide bone scanning, and head CT or magnetic resonance imaging. There is some doubt as to the usefulness of all of these studies, but various institutions use them routinely despite their high cost and questionable clinical benefit (5,6,13–16).

Thoracic CT is almost uniformly performed to stage lung cancer because it provides information about the primary lesion, thoracic lymph nodes, pleura, chest wall, and upper abdomen. What is uncertain is whether the routine use of intravenous contrast material or imaging of the entire contrast-enhanced liver is warranted. To our knowledge, there are no studies showing that additional information regarding the primary lesion, intrathoracic lymph nodes, or extrathoracic sites obtained with enhanced images has an effect on patient management.

In a number of studies, the use of contrast-enhanced CT for delineating and defining the primary lung mass in relationship to surrounding structures has been evaluated, but the additional information obtained with the routine use of contrast material does not appear to substantially change clinical treatment of the patient (1,4,5,17). Contrast-enhanced CT might permit identification of additional hilar or mediastinal lymph nodes, particularly for clinicians who do not routinely interpret these studies, but its findings do not necessarily reflect the true pathologic stage (7,18–20). In fact, some patients with small, normal-sized nodes at CT will have microscopic disease and, thus, disease will be understaged radiologically (20). Other patients will have enlarged reactive nodes and, thus, disease will be overstaged (1,6,18,19,21). In most series, CT is only 60% sensitive and specific for lymph node metastases (1,3,4). In one study, 37% of lymph nodes larger than 2 cm in diameter in patients with lung cancer were reactive and not neoplastic (22). Thus, tissue sampling should be performed in all surgical candidates to determine the pathologic stage. In the current study, enlarged abnormal lymph nodes were adequately seen with both CT examinations. Only two patients had a change in the nodal status (N0 to N1 and N3 to N1). This, however, did not alter patient treatment because, at our institution, patients who are candidates for resection undergo mediastinoscopy for pathologic staging.

Intraabdominal sites of lung metastases frequently include the adrenal glands and liver (23–25). The adrenal glands are equally well visualized on nonenhanced and contrast-enhanced images, although the results of many current studies suggest that characterization of adrenal abnormalities is, in fact, better with nonenhanced imaging (26–30). It is not clear at this time whether contrast-enhanced studies, even those performed with delayed imaging, will improve the characterization of adrenal abnormalities (31–34).

Although dedicated abdominal contrast-enhanced helical CT studies have yielded an increased rate of hepatic lesion detection (11,35–37), our literature search yielded no studies that addressed the clinical importance of lesions seen only at contrast-enhanced CT in patients with lung cancer. In our study, the metastatic status of patients did not change with contrast enhancement. When small (<5-mm) low-attenuating lesions in the liver that were too small to further characterize were demonstrated, they were considered to be benign, as suggested by results of prior investigations (11). All of the patients with small, low-attenuating lesions who underwent curative surgery were followed-up clinically or with CT (up to 5 months), and at the time this article was written, no case of hepatic metastasis had been detected. Furthermore, no patient with otherwise resectable disease has had pathologically proved isolated hepatic metastases that were seen only on contrast-enhanced images. All of the patients in our series who had hepatic metastases also had other pathologically documented disease in mediastinal lymph nodes, distant sites (including the brain, bone, or adrenal gland), or both. Thus, the frequency of true isolated hepatic metastases in patients who are candidates for surgery is probably rare. The detection of additional hepatic lesions in patients with liver metastases is of no clinical consequence because none of these patients would undergo resection.

There are several limitations to this study: There was minimal follow-up to ensure accurate staging in some patients, definitive tissue samples were not taken of all suspicious lesions, and there was the inherent selection bias of a tertiary care institution. In this study, however, we addressed a very specific question: Do stage and management change with use of contrast material? We believe the limitations of the study did not have a substantial effect on the outcome. We had to keep the study simple so that any institution can easily duplicate our results.

The results of our study suggest that nonenhanced thoracic CT through the adrenal glands is sufficient for successful radiologic staging in patients with newly diagnosed lung cancer. This has now become a standard procedure at our institution. Contrast-enhanced CT of the thorax did not substantially alter patient treatment, and routine contrast-enhanced CT through the liver is not required.


   Footnotes
 
Author contributions: Guarantor of integrity of entire study, E.F.P.; study concepts, E.F.P., P.C.G.; study design, E.F.P., H.P.M., P.C.G.; definition of intellectual content, all authors; literature research, E.F.P., J.J.E., H.P.M.; clinical studies, all authors; data acquisition, E.F.P., J.J.E., H.P.M.; data analysis, all authors; statistical analysis, J.E.H.; manuscript preparation, editing, and review, all authors.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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