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DOI:10.2214/AJR.07.3581
AJR 2008; 191:753-757
© American Roentgen Ray Society

Original Research

Tumor Staging of Advanced Esophageal Cancer: Combination of Double-Contrast Esophagography and Contrast-Enhanced CT

Yuichiro Yamabe1, Yoshifumi Kuroki1, Tsutomu Ishikawa2, Kunihisa Miyakawa3, Seiko Kuroki4 and Ryuzo Sekiguchi1

1 Department of Diagnostic Imaging, Tochigi Cancer Center, 4-9-13 Yonan, Utsunomiya-shi, Tochigi 3200834, Japan.
2 Department of Radiology, Dokkyo Medical University Hospital, Shimotsuga-gun, Tochigi, Japan.
3 Nagano PET Imaging and Diagnostic Center, Magano-shi, Japan.
4 National Cancer Center, Research Center for Cancer Prevention and Screening, Cancer Screening Division, Tokyo, Japan.

Received December 24, 2007; accepted after revision March 6, 2008.

 
Address correspondence to Y. Yamabe (y-yamabe{at}jb3.so-net.ne.jp).


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The objective of this study was to compare the diagnostic accuracy of tumor staging in patients with advanced esophageal cancer based on contrast-enhanced CT findings alone with that based on a combination of CT and double-contrast esophagography and to evaluate the relevance of tumor stage to survival rate.

MATERIALS AND METHODS. In 94 patients who underwent surgery as the primary treatment for esophageal cancer and had a diagnosis of postoperative T stage 3 (pT3) or pT4 disease based on pathologic examination, T stage was evaluated using CT alone and using a combination of CT and double-contrast esophagography. The diagnostic criterion for T4 disease using CT alone was tumor strongly displacing or deforming adjacent organs. The diagnostic criterion for T4 disease using the combined method was tumor displacing or deforming adjacent organs in the direction that corresponded to the direction of the location of the tumor or the deepest ulcer as diagnosed by barium esophagography. Concordance of T staging based on imaging with postoperative T staging based on pathology results, the gold standard, and survival rate were assessed for CT alone and for the combined method.

RESULTS. The concordance rate with postoperative T staging pathology results was 78% for CT alone and 84% for CT and double-contrast esophagography combined, with a significant difference between the two diagnostic methods. For patients with a diagnosis of T3 and those with a diagnosis of T4 using CT alone, the 3-year survival rate was 42% and 26%, respectively, with no significant difference between the two. For patients with a diagnosis of T3 and those with a diagnosis of T4 using the combined method, the 3-year survival rate was 42% and 21%, respectively, with a significant difference between the two.

CONCLUSION. The diagnostic performance of contrast-enhanced CT and double-contrast esophagography combined in staging advanced esophageal tumors is better than that of CT alone and thus has potential for estimating prognosis.

Keywords: CT • double-contrast esophagography • esophageal cancer • esophagography • survival curve • T stage


Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Although advanced esophageal cancer is still one of the many refractory cancers, we have seen remarkable recent advances in treatment. The 5-year survival rate for patients with esophageal cancer who underwent radical surgery has recently been reported to be 54% [1]. Favorable results—comparable to those obtained with surgery—have also been obtained with chemoradiation therapy [2, 3]. For prognosis assessment and treatment selection, accurate staging is crucial. Until recently, conclusive staging of esophageal cancer was determined by postoperative pathologic examination. However, because of the more widespread use of chemoradiation therapy in this setting, fewer postoperative pathologic samples will be available. Therefore, clinical staging of esophageal cancer based on diagnostic imaging before treatment will assume an increasingly important role.

In this study, we examined the usefulness of combining contrast-enhanced CT, which currently plays a major role in tumor staging of advanced esophageal cancer, with double-contrast esophagography; analyzed the diagnostic accuracy of CT alone and that of the combined method; and assessed the relevance of tumor stage to survival rate.


Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
In this study, contrast-enhanced CT and double-contrast esophagography were performed in all patients. Endoscopic sonography was performed as a standard evaluation in most T1 and T2 cases, but endoscopic sonography was not performed in all T3 and T4 cases. The study subjects were patients with esophageal cancer who underwent contrast-enhanced CT and double-contrast esophagography before undergoing surgery between 1995 and 1998 at one of three facilities. Subjects underwent surgery as the primary treatment for esophageal cancer, and postoperative T stage 3 (pT3) or pT4 was diagnosed on the basis of pathologic examination. Because evaluation of T1 and T2 esophageal lesions is difficult using CT and because the primary tumor in T1 and T2 cases does not infiltrate other organs, we excluded patients with T1 and T2 disease from our study group. In addition, patients with cervical esophageal cancer, distant metastases, multiple cancers, or serious comorbidities were excluded. Patients with primary small cell carcinoma or with primary adenocarcinoma were also excluded from the study because these histologic types are rare in Japan and prognosis differs from that of patients with squamous cell carcinoma.

Ninety-four patients (85 men, nine women) between the ages of 42 and 81 years (median, 65 years) were included in this study. On the basis of postoperative pathology results, 62 cases were diagnosed as pT3 and 32 cases, as pT4.

Single-detector helical CT scanners were used in the study and included HighSpeed Advantage (GE Healthcare), Xvigor Laudator (Toshiba Medical Systems), and Xvigor (Toshiba Medical Systems) units. Images were obtained while 2 mL/kg of nonionic iodinated contrast medium (300 mg I/mL) was injected at a rate of 1.5–3 mL/s into the median cubital vein. Transaxial images obtained during the portal phase with a slice thickness of 7 mm were used for analysis. For double-contrast esophagography, 100–300 mL of barium was administered orally and the effer vescent agent was used in all patients. Also, scopolamine butylbromide in dose of 20 mg was injected intramuscularly as an anticholinergic agent.

Cases were diagnosed as T3 or T4 disease on the basis of contrast-enhanced CT images alone or a combination of CT and double-contrast esophagography images. The diagnostic criteria for T4 were the following: for CT alone, adjacent organs show a convex inward or flattened deformity by tumor; and for the combined method, adjacent organs show a convex inward or flattened deformity by the tumor and the direction of the adjacent organs' displacement or deformation corresponds to the direction of the primary tumor or the deepest ulcer of the tumor as diagnosed by barium esophagography. Diagnoses were made by the consensus of five radiologists specializing in diagnostic gastrointestinal imaging.

T stage concordance was assessed using postoperative T staging (pTs) pathology results as the gold standard. Survival rates were calculated using the Kaplan-Meier method, and survival rates for patients with T3 and T4 disease based on CT alone as well as those for patients with T3 and T4 disease based on the combined method were compared using the log-rank test.


Figure 1
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  		Fig. 1A —78-year-old man with type 2 esophageal cancer located in medial thoracic esophagus. Tumor was 105 mm; survival period was 2,694 days. Transaxial contrast-enhanced CT scan through level of left mainstem bronchus shows flattening of posterior wall. Diagnosis using CT alone was T4 based on invasion of bronchus.

 


Figure 2
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  		Fig. 1B —78-year-old man with type 2 esophageal cancer located in medial thoracic esophagus. Tumor was 105 mm; survival period was 2,694 days. Frontal double-contrast esophagogram shows tumor and deepest ulcer are on right posterior wall on opposite side of left main bronchus. These findings led to diagnosis of T3 using CT and double-contrast esophagography. Postoperative pathology revealed no invasion of left main bronchus.

 

Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The locations of the tumors based on the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus (9th edition) [4] were the upper thoracic esophagus in 18 cases, middle thoracic esophagus in 44 cases, lower thoracic esophagus in 19 cases, and abdominal esophagus in 13 cases. Macroscopic tumor types were one type 1 case, 69 type 2 cases, 20 type 3 cases, and four type 4 cases. The median tumor length was 75 mm for patients with pT3 disease and 87.5 mm for pT4 cases.

Sixty-three cases and 31 cases were diagnosed as T3 and T4, respectively, on the basis of CT alone with a concordance rate with pathology results of 78%; 10 cases were overstaged and 11, understaged. Sixty-four and 30 cases were diagnosed as T3 and T4, respectively, on the basis of CT and double-contrast esophagography with a concordance rate of 84%; five cases were overstaged and 11, understaged. None of the cases was diagnosed as T1 or T2 using either diagnostic method.

The tumor stage based on CT images alone was changed with the addition of double-contrast esophagography images in 17 cases: 10 imaging diagnoses were changed from T4 to T3 (seven were in concordance with the pathologic diagnosis) and seven, from T3 to T4 (five of these diagnoses were concordant with pathologic diagnosis) (Figs. 1A, 1B and 2A, 2B).


Figure 3
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  		Fig. 2A —55-year-old man with type 2 esophageal cancer located in upper thoracic esophagus. Tumor was 80 mm; survival period was 320 days. Transaxial contrast-enhanced CT scan through level of primary bronchus shows convex inward deformity of posterior wall. Diagnosis of T4 was made using CT alone based on invasion of bronchus.

 

Figure 4
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  		Fig. 2B —55-year-old man with type 2 esophageal cancer located in upper thoracic esophagus. Tumor was 80 mm; survival period was 320 days. Frontal double-contrast esophagogram shows tumor and deepest ulcer are on left posterior wall on opposite side of primary main bronchus, leading to diagnosis of T3 using CT and double-contrast esophagography. Postoperative pathology revealed no invasion of primary main bronchus.

 
For patients with pT3 and pT4 disease, the median survival time was 792 and 256 days, respectively, and the 3-year survival rate was 44% and 19%, respectively (Fig. 3). A statistically significant difference in the survival rates of patients with pT3 and those with pT4 disease was observed by the log-rank test (p = 0.001). For cases of T3 and T4 disease diagnosed using CT alone, the median survival time was 644 and 367 days, respectively, and the 3-year survival rate was 42% and 26%, respectively (Fig. 4). No clear significant difference in survival rates of T3 and T4 was observed by the log-rank test (p = 0.055). In contrast, for T3 and T4 cases diagnosed using the combined method, the median survival time was 783 and 263 days, respectively, and the 3-year survival rate was 42% and 21%, respectively; a statistically significant difference in survival rates was noted between the two groups (p = 0.024) (Fig. 5).


Figure 5
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  		Fig. 3 —Survival curve of pT3 and pT4 cases. For patients with pT3 disease, 3-year survival rate was 44% and median survival time was 792 days. For patients with pT4 disease, 3-year survival rate was 19% and median survival time was 256 days. Significant difference was observed between two stages (p = 0.001).

 

Figure 6
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  		Fig. 4 —Survival curve of T3 and T4 cases diagnosed using CT alone. For patients with T3 disease, 3-year survival rate was 42% and median survival time was 644 days. For patients with T4 disease, 3-year survival rate was 26% and median survival time was 367 days. No significant difference was observed between two stages (p = 0.055).

 

Figure 7
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  		Fig. 5 —Survival curve of T3 and T4 cases diagnosed using both CT and double-contrast esophagography. For patients with T3 disease, 3-year survival rate was 42% and median survival time was 783 days. For patients with T4 disease, 3-year survival rate was 21% and median survival time was 263 days. Significant difference was observed (p = 0.024).

 


Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Esophageal cancer is a highly malignant cancer that develops lymph node or distant metastases in its early stage and invades the surrounding organs. Even with advanced treatment modalities, the 5-year survival rates by histologic staging categories remain 78.2% for stage 0, 67.8% for stage I, 60.4% for stage II, 33.9% for stage III, and 15.8% for stage IV [1].

Although esophageal cancer is still a typical refractory cancer, treatment outcomes have improved because of advances in various treatment methods especially chemoradiation therapy, which has been reported to be comparable to surgery [5]. Ishikura et al. [3] reported favorable results for chemoradiation therapy, observing a median survival time of 44 months and a 5-year survival rate of 49% for T3 or T4N(any)M0 cases and a median survival time of 11 months and 5-year survival rate of 13% for T4, M1, or T4 M1 lymph node cases. In addition, methods that use chemoradiation as a preoperative treatment have been developed [6–8].

With these advances, T stage diagnosis using postoperative pathologic samples may become difficult in many cases in the future. Pretreatment diagnostic imaging has a substantial impact on treatment choice. Thus, improved accuracy of the pretreatment imaging diagnosis to estimate prognosis is desired. T stage diagnosis using CT has been reported by many researchers [9–17].

With regard to the diagnosis of aortic invasion, Picus et al. [9] showed that the area of contact between tumor and the aorta tends to be greater when esophageal cancer invades the aorta. These researchers advocated a method of determining the presence or absence of aortic invasion using the contact area between the tumor and aorta: Invasion is indicated when ≥ 90° of the aortic circumference is in contact with the tumor, and no invasion is indicated when ≤ 45° of the aortic circumference is in contact with the tumor. These diagnostic criteria are widely used today. With regard to tracheal invasion, Thompson et al. [11] reported that tracheal invasion is indicated by CT images showing tumor displacing or deforming the trachea. However, in our experience, this criterion tends to lead to overstaging.

With advances in equipment and instruments, MDCT and MRI are being applied to T staging of advanced esophageal cancer, but studies about these imaging methods in this setting have focused mainly on comparing staging based on imaging with staging based on pathologic results and have seldom analyzed the relationship of T stage to prognosis [18–21].

For the present study, we evaluated the possibility of improving diagnostic accuracy, including the estimation of outcome, by determining the primary location and direction of the esophageal cancer ulcer with contrast-enhanced CT. Diagnoses based on CT and double-contrast esophagography combined showed higher concordance with pathologic diagnoses than with those based on CT alone. The diagnoses based on the combined method also showed a significant difference in survival rates between patients with T3 and T4 disease, although those based on CT alone did not. One reason for the discrepancy may be that some cases were downstaged from T4 to T3 because of the information provided by double-contrast esophagography.

The depth of invasion of esophageal cancer is easily inferred to be greatest in the direction of the ulcer. For cases in which the direction of displacement or deformation of the surrounding organs by tumor on the CT images is discordant with information provided by double-contrast esophagography, the CT findings should not be considered definitive. For these reasons, the combined approach may have reduced the possibility of overstaging. Double-contrast esophagography, in addition to CT and MRI, clearly depicts esophageal cancer morphology, including ulcers, and should be actively used for T staging in the future.

The present study may have limitations. All subjects were patients who had undergone surgical treatment of esophageal cancer. We chose these patients to enable exact comparisons with pathologic samples, but as a result, highly advanced T4 cases were excluded from the study group, which may have increased the number of cases that were near the boundary of T3 and T4. Another possible limitation is that single-detector helical CT was used rather than the now commonly used MDCT. As a result, precise multiplanar reconstructions were difficult to create and may have improved the diagnostic performance of CT alone. However, despite these limitations double-contrast esophagography combined with CT and MRI may be useful for improved T stage diagnosis and prognosis estimation.

Chemoradiation therapy will account for an important treatment option for patients with esophageal cancer in the future. Even in cases in which postoperative pathologic samples cannot be obtained, accurate staging that allows estimation of outcome is required and improved accuracy of pretreatment imaging diagnosis is needed. A combined imaging diagnosis that integrates double-contrast eso phagography findings with conventional CT findings will have an important role in the diagnosis of advanced esophageal cancer.


References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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