Clinical News & Knowledge: Esophageal Cancer
January 1, 2005
Oncology.
CHAPTER 12
Esophageal cancer
I. Benjamin Paz, MD, Jimmy J. Hwang, MD,
Rajesh Iyer, MD, and Lawrence Coia, MD
Although still relatively uncommon in Western countries, esophageal cancer is
fatal in the vast majority of cases. In the United States, an estimated 14,520 new
cases will be diagnosed in the year 2005, and 13,570 deaths will result from the
disease. This high percentage of deaths rivals that of pancreatic cancer and is
more than four times that of rectal cancer.
The esophagus extends from the cricopharyngeal sphincter to the gastroesophageal
(GE) junction and is commonly divided into the cervical, upper to
mid-thoracic, and thoracic portions. This can be important, as histology and
optimal treatment approaches may vary considerably based on the site of the
cancer. It may not be possible to determine the site of origin if the cancer involves
the GE junction itself.
Epidemiology
Gender Esophageal cancer is seven times more common and slightly more
lethal in men than in women.
Age Adenocarcinoma of the esophagus (now more common in the United
States than the squamous cell type) has a median age at diagnosis of 69 years.
The incidence of squamous cell cancer of the esophagus increases with age as
well and peaks in the seventh decade of life.
Race The incidence of squamous cell esophageal cancer is three times higher
in blacks than in whites, whereas adenocarcinomas are more common in white
men.
Geography Evidence for an association between environment and diet and
esophageal cancer comes from the profound differences in incidence observed
in different parts of the world. Esophageal cancer occurs at a rate 20-30 times
higher in China than in the United States. An esophageal "cancer belt" extends
from northeast China to the Middle East.
Survival Although the overall outlook for patients diagnosed with esophageal
cancer has improved in the past 30 years, most patients still present with advanced
disease, and their survival remains poor. One-third to one-half of patients
treated with either chemoradiation therapy or chemoradiation therapy
plus surgery are alive at 2 years, without recurrence of esophageal cancer.
Disease site The rate of cancer of the distal esophagus is about equal to that of
the more proximal two-thirds. In general, squamous cell carcinoma is found in
the body of the esophagus, whereas adenocarcinoma predominates in lesions
closer to the GE junction.
Etiology and risk factors
Cigarettes and alcohol Squamous cell carcinomas of the esophagus have been
associated with cigarette smoking and/or excessive alcohol intake. Furthermore,
cigarette smoking and alcohol appear to act synergistically, producing high
relative risks in heavy users of tobacco and alcohol. Esophageal adenocarcinoma
is increased twofold in smokers.
Diet High-fat, low-protein, and low-calorie diets have been shown to increase
the risk of esophageal cancer. Exposure to nitrosamines has been proposed as
a factor in the development of both squamous cell carcinoma and adenocarcinoma
of the esophagus.
Barrett's esophagus and other factors Gastroesophageal reflux disease
(GERD) and Barrett's esophagus (adenomatous metaplasia of the distal esophagus)
have been linked to adenocarcinoma of the esophagus. Tylosis, Plummer-
Vinson syndrome, history of head and neck cancer, and achalasia have also
been associated with a higher-than-normal risk of developing squamous cell
cancer of the esophagus.
Signs and symptoms
Because symptoms do not alert the patient until the disease is advanced, few
esophageal cancers are diagnosed at an early stage.
Dysphagia The most common presenting complaint is dysphagia, which generally
is not noted until the esophageal lumen is narrowed to one-half to onethird
of normal, due to its elasticity.
Weight loss is common and has a significant role in prognosis (> 10% of total
body weight as poor prognosis).
Cough that is induced by swallowing is suggestive of local extension into the
trachea with resultant tracheoesophageal fistula.
Odynophagia and pain Pain with swallowing (odynophagia) is an ominous
sign. Patients who describe pain radiating to the back may well have extraesophageal
spread. Supraclavicular or cervical nodal metastases may be appreciated
on examination.
Hoarseness may be a sign of recurrent laryngeal nerve involvement due to
extraesophageal spread.
Metastatic disease may present as malignant pleural effusion or ascites. Bone
metastasis can be identified by pain involving the affected site or by associated
hypercalcemia. The most common metastatic sites are retroperitoneal or celiac
lymph nodes.
The American College of Surgeons conducted a study utilizing its national cancer
database to assess the presentation, stage distribution, and treatment of pa-
tients diagnosed with esophageal cancer between 1994 and 1997 (n = 5,044).
The most common presenting symptoms were dysphagia (74.0%), weight loss
(57.3%), reflux (20.5%), odynophagia (16.6%), and dyspnea (12.1%). Fifty percent
of patients had tumors located in the lower third of the esophagus. Squamous
cell histology was found in 51.6%, and 42.0% of patients had adenocarcinomas.
Barrett's esophagus was found in 39% of those patients with adenocarcinoma.
Patients undergoing initial surgical resection had the following stage
distribution: stage I (13.3%), II (34.7%), III (35.7%), and IV (12.3%).
Diagnosis
In Western countries, the diagnosis of esophageal cancer is generally made by
endoscopic biopsy of the esophagus. In the Far East, cytologic evaluation is
frequently utilized.
Endoscopic ultrasonography (EUS) is extremely accurate (> 90%) in establishing
the depth of tumor invasion (T stage) but less accurate (70%-80%) in
determining nodal involvement (N stage) unless combined with fine-needle
aspiration (FNA) of the involved nodes (93% accuracy) when nodes greater
than 5 mm are biopsied. The addition of FNA increases the sensitivity from
63% to 93% and the specificity from 81% to 100%. EUS is not reliable in determining
the extent of response to neoadjuvant treatment.
Endoscopy and barium x-rays Endoscopy allows for direct visualization of
abnormalities and directed biopsies. Barium x-rays are less invasive and provide
a good assessment of the extent of esophageal disease.
Bronchoscopy should be performed to detect tracheal invasion in all cases of
esophageal cancer except adenocarcinoma of the distal third of the esophagus.
CT scan Once a diagnosis has been established and careful physical examination
and routine blood tests have been performed, a CT scan of the chest, abdomen,
and pelvis should be obtained to help assess tumor extent, nodal involvement,
and metastatic disease.
PET A prospective trial designed to evaluate the utility of PET vs CT and EUS
was performed by obtaining these studies in 48 consecutive patients prior to
esophagectomy. PET achieved a 57% sensitivity, 97% specificity, and 86% accuracy
compared with CT, which was 99% sensitive, 18% specific, and 78% accurate.
In terms of nodal staging, PET was correct in 83% of cases, as compared
with 60% of cases for CT and 58% for EUS (P = .006). This analysis suggests the
improved accuracy of PET in the staging work-up of patients with esophageal
cancer.
Numerous studies report the accuracy of PET scanning in determining the presence
of metastatic disease, with sensitivity approaching 90% and specificity
over 90%.
As PET becomes more widely available, its use will probably become an important
part of the preoperative evaluation of these patients. In a prospective
trial of 39 patients with esophageal cancer, PET detected additional sites of
metastatic disease at the initial evaluation when compared with conventional
imaging. After induction therapy, PET did not
add to the estimation of locoregional resectability
and did not detect new distant metastases.
However, this study suggested that
changes in [18fluorodeoxyglucose] FDG-PET
following induction therapy may predict disease-
free and overall survival after induction
therapy and resection in patients with esophageal
cancer. A large prospective national trial
will evaluate the use of PET scan in the treatment
of esophageal cancer.
Bone scan A bone scan should be obtained
if the patient has bone pain or an elevated alkaline
phosphatase level.
Thoracoscopy/laparoscopy Investigators have recently begun to examine the
role of surgical staging prior to definitive therapy. These procedures are designed
to allow pathologic review of regional lymph nodes and the accurate
assessment of extraesophageal tumor spread by direct visualization. A recently
completed multi-institution trial (Cancer and Leukemia Group B [CALGB]
9380) found these procedures to be feasible in over 70% of patients; they resulted
in the upstaging of patients in 38% of cases reviewed. Further investigations
need to be completed to determine the appropriate use of these tools in
treatment algorithms for patients with esophageal cancer.
Warning Staging studies should be undertaken only if management would
change on the basis of specific findings.
Screening and surveillance
HIGH-RISK PATIENTS
Adenocarcinoma The role of screening patients with GERD and surveillance
of patients with Barrett's esophagus by upper GI endoscopy remains under
investigation. In 833 patients studied by endoscopy, there was a 13% incidence
of intestinal metaplasia (Barrett's esophagus). Dysplasia or cancer was seen in
31% of patients with long-segment Barrett's esophagus, in 10% of short-segment
Barrett's esophagus, and in 6% of GE-junction intestinal metaplasia.
Squamous cell carcinoma Mass screening in the high-risk areas of China and
Japan is considered appropriate.
Pathology
Adenocarcinoma The incidence of esophageal adenocarcinoma involving the
GE junction has risen 4%-10% per year since 1976 in the United States and
Europe. As a result, adenocarcinoma is now the predominant histologic subtype
of esophageal cancer. The distal one-third of the esophagus is the site of
origin of most adenocarcinomas.
Squamous cell carcinomas occur most often in the proximal two-thirds of
the esophagus. Squamous cell carcinoma is still the most prevalent histologic
subtype worldwide.
Other tumor types Other, less frequently seen histologic subtypes include
mucoepidermoid carcinoma, small-cell carcinoma, sarcoma, adenoid cystic
leiomyosarcoma, and primary lymphoma of the esophagus. Occasionally, metastatic
disease from another site may present as a mass in the esophagus or a
mass pressing on the esophagus.
Metastatic spread The most common sites of metastatic disease are the regional
lymph nodes, lungs, liver, bone, adrenal glands, and diaphragm. Adenocarcinoma
can also metastasize to the brain.
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