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PDQ®
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Esophageal cancer is a treatable disease that is rarely curable. The overall five-year survival rate in those cases amenable to surgery ranges from 5% to 20%. The occasional patient with very early disease has a better chance of survival. Primary treatment modalities include surgery alone or chemotherapy with radiation therapy. Combined modality therapy (chemotherapy plus surgery, or chemotherapy and radiation therapy plus surgery) is under clinical evaluation. Effective palliation may be obtained in individual cases with various combinations of surgery, chemotherapy, radiation therapy, stents,[1] photodynamic therapy,[2-4] and endoscopic therapy with Nd:YAG laser.[5]
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Approximately 50% of esophageal cancers are squamous cell carcinomas. Adenocarcinomas, typically arising in Barrett's esophagus, account for the other 50% of malignant lesions, and the incidence of this histology appears to be rising. Barrett's esophagus contains glandular epithelium cephalad to the esophagogastric junction. Three different types of glandular epithelium can be seen: metaplastic columnar epithelium, metaplastic parietal cell glandular epithelium within the esophageal wall, or metaplastic intestinal epithelium with typical goblet cells. Dysplasia is particularly likely to develop in the intestinal mucosa.
Treatment
The stage determines whether the intent of the therapeutic approach will be
curative or palliative. The American Joint Committee on Cancer (AJCC) has
designated staging by TNM classification.[1]
-- TNM definitions --
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor invades lamina propria or submucosa
T2: Tumor invades muscularis propria
T3: Tumor invades adventitia
T4: Tumor invades adjacent structures
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Distant metastasis (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
Tumors of the lower thoracic esophagus:
M1a: Metastasis in celiac lymph nodes
M1b: Other distant metastasis
Tumors of the midthoracic esophagus:
M1a: Not applicable
M1b: Nonregional lymph nodes and/or other distant metastasis
Tumors of the upper thoracic esophagus:
M1a: Metastasis in cervical nodes
M1b: Other distant metastasis
For tumors of midthoracic esophagus use only M1b, since these tumors with
metastasis in nonregional lymph nodes have an equally poor prognosis as those
with metastasis in other distant sites.
-- AJCC stage groupings --
-- Stage 0 --
Tis, N0, M0
-- Stage I --
T1, N0, M0
-- Stage IIA --
T2, N0, M0
T3, N0, M0
-- Stage IIB --
T1, N1, M0
T2, N1, M0
-- Stage III --
T3, N1, M0
T4, Any N, M0
-- Stage IV --
Any T, Any N, M1
-- Stage IVA --
Any T, Any N, M1a
-- Stage IVB --
Any T, Any N, M1b
The current staging system for esophageal cancer is based largely on retrospective data from the Japanese Committee for Registration of Esophageal Carcinoma. It is most applicable to patients with squamous carcinomas of the upper- and middle-thirds of the esophagus, as opposed to the increasingly common distal esophageal and gastroesophageal junction adenocarcinomas.[2] In particular, the classification of involved abdominal lymph nodes as M1 disease has been criticized. The presence of positive abdominal lymph nodes does not appear to carry as grave a prognosis as metastases to distant organs.[3] Patients with regional and/or celiac axis lymphadenopathy should not necessarily be considered to have unresectable disease due to metastases. Complete resection of the primary tumor and appropriate lymphadenectomy should be attempted when possible.
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The prevalence of Barrett's metaplasia in adenocarcinoma of the esophagus suggests that Barrett's esophagus may be a premalignant condition. Strong consideration should be given to resection in patients with high-grade dysplasia in the setting of Barrett's metaplasia. Endoscopic surveillance of patients with Barrett's metaplasia may detect adenocarcinoma at an earlier stage more amenable to curative resection.[1] The survival rate of patients with esophageal cancer is poor. Asymptomatic small tumors confined to the esophageal mucosa or submucosa are detected only by chance. Surgery is the treatment of choice for these small tumors. Once symptoms are present (dysphagia, in the majority of cases), esophageal cancers have usually invaded the muscularis propria or beyond and may have metastasized to lymph nodes or other organs.
In the presence of complete esophageal obstruction, without clinical evidence of systemic metastasis, surgical excision of the tumor with mobilization of the stomach to replace the esophagus has been the traditional means of relieving the dysphagia. In the United States, the median age of patients who present with esophageal cancer is 67 years of age.[2] The results of a retrospective review of 505 consecutive patients who were operated on by a single surgical team over 17 years found no difference in the perioperative mortality, median survival, or palliative benefit of esophagectomy on dysphagia when the group of patients older than 70 were compared to their younger peers.[3][Levels of evidence: 3iiA, 3iiB] All of the patients in this series were selected for surgery based on potential operative risk. Age alone should not determine therapy for patients with potentially resectable disease.
There is controversy as to the optimal surgical procedure, transhiatal esophagectomy with anastomosis of the stomach to the cervical esophagus versus an abdominal mobilization of the stomach and transthoracic excision of the esophagus with anastomosis of the stomach to the upper thoracic esophagus or the cervical esophagus. In patients with partial esophageal obstruction, dysphagia may, at times, be relieved by placement of an expandable metallic stent [4] or, rarely, by radiation therapy. Alternative methods of relieving dysphagia have been reported, including laser therapy and electrocoagulation to destroy intraluminal tumor.[5-8]
Surgical treatment of resectable esophageal cancers results in 5-year survival rates of 5% to 20%, with higher survival rates in patients with early stage cancers. This is associated with a less than 10% operative mortality rate.[9] In an attempt to avoid this perioperative mortality and to relieve dysphagia, definitive radiation therapy in combination with chemotherapy has been studied. One series from Fox Chase, evaluating radiation therapy and chemotherapy with fluorouracil and mitomycin, produced a 75% local control rate, associated with improved swallowing, and a 30% actuarial disease-free survival (18% overall survival) at 5 years for stage I and stage II patients.[10] An intergroup randomized trial of chemotherapy and radiation therapy versus radiation therapy alone resulted in an improvement in 5-year survival for the combined modality group (26% versus 0%).[11] An Eastern Cooperative Oncology Group trial of 135 patients showed that chemotherapy plus radiation provided a better 2-year survival rate than radiation therapy alone,[12] similar to that shown in the Radiation Therapy Oncology Group trial. A number of phase II studies have suggested improved survival with induction chemoradiotherapy followed by resection when compared with surgery-only historical controls.[13-18] Approximately 25% of patients achieve a complete pathologic response, albeit in some series at the cost of increased postoperative morbidity and mortality. A multicenter prospective randomized trial in which preoperative combined chemotherapy (cisplatin) and radiation therapy (3,700 cGy in 370 cGy fractions) followed by surgery were compared with surgery alone in patients with squamous cell carcinoma showed no improvement in overall survival and a significantly higher postoperative mortality (12% versus 4%) in the combined modality arm.[19] In patients with adenocarcinoma of the esophagus, a single institution phase III trial demonstrated a modest survival benefit (16 months versus 11 months) for patients treated with induction chemoradiotherapy consisting of 5-fluorouracil, cisplatin, and 4,000 cGy (267 cGy fractions) plus surgery over resection alone.[20] The small sample size, short follow-up, early stoppage based on interim analysis, disproportionate number of patients withdrawn from the combined modality arm, and lack of stratification based on pretreatment stage are some of the concerns regarding this trial. Therefore, the role of combined modality therapy remains unproven. The results of a national intergroup study showed no statistically significant difference in disease-free or overall survival for preoperative and postoperative chemotherapy alone over surgery alone for adenocarcinoma or squamous cell carcinoma of the esophagus.[21]
Special attention to nutritional support is indicated in any patient undergoing treatment of esophageal cancer. Further progress in clinical management awaits a study comparing definitive radiation therapy to surgical excision in patients who have responded to initial chemotherapy. All newly diagnosed patients should be considered candidates for new therapies and clinical trials comparing various treatment modalities. The majority of clinical studies have dealt with squamous cell carcinomas. As previously noted, the incidence of adenocarcinoma arising in Barrett's esophagus is increasing. Whether these adenocarcinomas are more or less sensitive to the chemotherapy and radiation used in the treatment of squamous cell carcinomas has not been established. Surgical excision remains standard therapy for these tumors; surgical adjuvants are under clinical evaluation. There has been no positive trial of postsurgical adjuvant therapy.
The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.
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Stage 0 esophageal cancer is not usually seen in the United States. Surgery for this stage of cancer is used successfully in Asia.
Treatment options:
Standard:
Treatment options:
Standard:
Treatment options:
Standard:
2. Surgical resection of T3 lesions.
Treatment options:
Standard:
2. Intraluminal brachytherapy can also provide palliation of dysphagia.[1,2]
3. Nd:YAG endoluminal tumor destruction or electrocoagulation.[3]
All recurrent esophageal cancer patients present difficult problems in palliation. All patients, whenever possible, should be considered candidates for clinical trials as outlined in treatment overview.
Treatment options:
Standard:
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