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Important: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Esophageal cancer


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
TREATMENT OPTION OVERVIEW
STAGE 0 ESOPHAGEAL CANCER
STAGE I ESOPHAGEAL CANCER
STAGE II ESOPHAGEAL CANCER
STAGE III ESOPHAGEAL CANCER
STAGE IV ESOPHAGEAL CANCER
RECURRENT ESOPHAGEAL CANCER

GENERAL INFORMATION

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]

References:

  1. Tietjen TG, Pasricha PJ, Kalloo AN: Management of malignant esophageal stricture with esophageal dilation and esophageal stents. Gastrointestinal Endoscopy Clinics of North America 4(4): 851-862, 1994.

  2. Lightdale CJ, Heier SK, Marcon NE, et al.: Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial. Gastrointestinal Endoscopy 42(6): 507-512, 1995.

  3. Kubba AK: Role of photodynamic therapy in the management of gastrointestinal cancer. Digestion 60(1): 1-10, 1999.

  4. Heier SK, Heier LM: Tissue sensitizers. Gastrointestinal Endoscopy Clinics of North America 4(2): 327-252, 1994.

  5. Bourke MJ, Hope RL, Chu G, et al.: Laser palliation of inoperable malignant dysphagia: initial and at death. Gastrointestinal Endoscopy 43(1): 29-32, 1996.


CELLULAR CLASSIFICATION

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.


STAGE INFORMATION


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.

References:

  1. Esophagus. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 65-69.

  2. Japanese Committee for Registration of Esophageal Carcinoma Cases: Parameters linked to ten-year survival in Japan of resected esophageal carcinoma. Chest 96(5): 1005-1011, 1989.

  3. Korst RJ, Rusch VW, Venkatraman E, et al.: Proposed revision of the staging classification for esophageal cancer. Journal of Thoracic and Cardiovascular Surgery 115(3): 660-670, 1998.


TREATMENT OPTION OVERVIEW

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.

References:

  1. Lerut T, Coosemans W, Van Raemdonck D, et al.: Surgical treatment of Barrett's carcinoma: correlations between morphologic findings and prognosis. Journal of Thoracic and Cardiovascular Surgery 107(4): 1059-1066, 1994.

  2. Ginsberg RJ: Cancer treatment in the elderly. Journal of the American College of Surgeons 187(4): 427-428, 1998.

  3. Ellis FH Jr, Williamson WA, Heatley GJ: Cancer of the esophagus and cardia: does age influence treatment selection and surgical outcomes? Journal of the American College of Surgeons 187(4): 345-351, 1998.

  4. Saxon RR, Morrison KE, Lakin PC, et al.: Malignant esophageal obstruction and esophagorespiratory fistula: palliation with a polyethylene-covered Z-stent. Radiology 202(2): 349-354, 1997.

  5. Campbell WR, Taylor SA, Pierce GE, et. al.: Therapeutic alternatives in patients with esophageal cancer. American Journal of Surgery 150(6): 665-668, 1985.

  6. Mellow MH, Pinkas H: Endoscopic therapy for esophageal carcinoma with Nd:Yag laser: prospective evaluation of efficacy, complications, and survival. Gastrointestinal Endoscopy 30(6): 334-339, 1984.

  7. Fleischer D, Sivak MV: Endoscopic Nd-YAG laser therapy as palliation for esophagogastric cancer: parameters affecting initial outcome. Gastroenterology 89(4): 827-831, 1985.

  8. Karlin DA, Fisher RS, Krevsky B: Prolonged survival and effective palliation in patients with squamous cell carcinoma of the esophagus following endoscopic laser therapy. Cancer 59(11): 1969-1972, 1987.

  9. Kelsen DP, Bains M, Burt M: Neoadjuvant chemotherapy and surgery of cancer of the esophagus. Seminars in Surgical Oncology 6(5): 268-273, 1990.

  10. Coia LR, Engstrom PF, Paul AR, et al.: Long-term results of infusional 5-FU, mitomycin-C, and radiation as primary management of esophageal carcinoma. International Journal of Radiation Oncology, Biology, Physics 20(1): 29-36, 1991.

  11. Cooper JS, Guo MD, Herskovic A, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG-85-01). Journal of the American Medical Association 281(17): 1623-1627, 1999.

  12. Smith TJ, Ryan LM, Douglass HO Jr., et al.: Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. International Journal of Radiation Oncology, Biology, Physics 42(2): 269-276, 1998.

  13. Forastiere AA, Orringer MB, Perez-Tamayo C, et al.: Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report. Journal of Clinical Oncology 11(6): 1118-1123, 1993.

  14. Poplin E, Fleming T, Leichman L, et al.: Combined therapies for squamous cell carcinoma of the esophagus, a Southwest Oncology Group Study (SWOG-8037). Journal of Clinical Oncology 5(4): 622-628, 1987.

  15. Stewart JR, Hoff SJ, Johnson DH, et al.: Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus. Annals of Surgery 218(4): 571-578, 1993.

  16. Urba SG, Orringer MB, Perez-Tamayo C, et al.: Concurrent preoperative chemotherapy and radiation therapy in localized esophageal adenocarcinoma. Cancer 69(2): 285-291, 1992.

  17. Stahl M, Wilke H, Fink U, et al.: Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer: interim analysis of a phase II trial. Journal of Clinical Oncology 14(3): 829-837, 1996.

  18. Bates BA, Detterbeck FC, Bernard SA, et al.: Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma. Journal of Clinical Oncology 14(1): 156-163, 1996.

  19. Bosset JF, Gignoux M, Triboulet JP, et al.: Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. New England Journal of Medicine 337(3): 161-167, 1997.

  20. Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. New England Journal of Medicine 335(7): 462-467, 1996.

  21. Kelsen DP, Ginsberg R, Pajak TF, et al.: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. New England Journal of Medicine 339(27): 1979-1984, 1998.


STAGE 0 ESOPHAGEAL CANCER

Stage 0 esophageal cancer is not usually seen in the United States. Surgery for this stage of cancer is used successfully in Asia.


STAGE I ESOPHAGEAL CANCER

Treatment options:

Standard:

Surgery.

Under clinical evaluation:
Clinical trials as outlined in treatment overview. Refer to PDQ and to
CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials
for patients with esophageal cancer.


STAGE II ESOPHAGEAL CANCER

Treatment options:

Standard:

1. Surgery.

2. Chemotherapy plus radiation therapy with or without subsequent surgery.[1,2]

Under clinical evaluation:
Clinical trials as outlined in treatment overview. Refer to PDQ and to
CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials
for patients with esophageal cancer.

References:

  1. Cooper JS, Guo MD, Herskovic A, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG-85-01). Journal of the American Medical Association 281(17): 1623-1627, 1999.

  2. Herskovic A, Al-Sarraf M: Combination of 5-fluorouracil and radiation in esophageal cancer. Seminars in Radiation Oncology 7(4): 283-290, 1997.


STAGE III ESOPHAGEAL CANCER

Treatment options:

Standard:

1. Chemotherapy plus radiation therapy with or without subsequent surgery.[1,2]

2. Surgical resection of T3 lesions.

Under clinical evaluation:
Clinical trials as outlined in treatment overview. Refer to PDQ and to
CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials
for patients with esophageal cancer.

References:

  1. Cooper JS, Guo MD, Herskovic A, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG-85-01). Journal of the American Medical Association 281(17): 1623-1627, 1999.

  2. Herskovic A, Al-Sarraf M: Combination of 5-fluorouracil and radiation in esophageal cancer. Seminars in Radiation Oncology 7(4): 283-290, 1997.


STAGE IV ESOPHAGEAL CANCER

Treatment options:

Standard:

1. Radiation therapy with or without intraluminal intubation and dilation.

2. Intraluminal brachytherapy can also provide palliation of dysphagia.[1,2]

3. Nd:YAG endoluminal tumor destruction or electrocoagulation.[3]

Under clinical evaluation:
Clinical trials as outlined in treatment overview. Refer to PDQ and to
CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials
for patients with esophageal cancer.

References:

  1. Sur RK, Donde B, Levin VC, et al.: Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer. International Journal of Radiation Oncology, Biology, Physics 40(2): 447-453, 1998.

  2. Gaspar LE, Nag S, Herskovic A, et al.: American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. International Journal of Radiation Oncology, Biology, Physics 38(1): 127-132, 1997.

  3. Bourke MJ, Hope RL, Chu G, et al.: Laser palliation of inoperable malignant dysphagia: initial and at death. Gastrointestinal Endoscopy 43(1): 29-32, 1996.


RECURRENT ESOPHAGEAL CANCER

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:

Palliative use of any of the standard therapies, including supportive care.

Under clinical evaluation:
Clinical trials as outlined in treatment overview. Refer to PDQ and to
CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials
for patients with esophageal cancer.

Date Last Modified: 11/1999



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