Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of esophageal cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

• Risk factors.
• Cellular classification.
• Staging.
• Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

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General Information

Note: Separate PDQ summaries on Prevention of Esophageal Cancer and Screening for Esophageal Cancer are also available.

Note: Estimated new cases and deaths from esophageal cancer in the United States in 2009:[1]

• New cases: 16,470.
• Deaths: 14,530.

The incidence of esophageal cancer has risen in recent decades, coinciding with a shift in histologic type and primary tumor location.[2][3] Adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and western Europe, with most tumors located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown.

While risk factors for squamous cell carcinoma of the esophagus have been identified (e.g., tobacco, alcohol, diet), the risk factors associated with esophageal adenocarcinoma are less clear.[3] The presence of Barrett esophagus is associated with an increased risk of developing adenocarcinoma of the esophagus, and chronic reflux is considered the predominant cause of Barrett metaplasia. The results of a population-based, case-controlled study from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively correlated with increased risk of esophageal adenocarcinoma.[4]

Esophageal cancer is a treatable disease, but it is rarely curable. The overall 5-year survival rate in patients amenable to definitive treatment ranges from 5% to 30%. The occasional patient with very early disease has a better chance of survival. Patients with severe dysplasia in distal esophageal Barrett mucosa often have in situ or even invasive cancer within the dysplastic area. Following resection, these patients usually have excellent prognoses.

Primary treatment modalities include surgery alone or chemotherapy with radiation therapy. Combined modality therapy (i.e., 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,[5] photodynamic therapy,[6][7][8] and endoscopic therapy with Nd:YAG laser.[9]

One of the major difficulties in allocating and comparing treatment modalities for patients with esophageal cancer is the lack of precise preoperative staging. Standard noninvasive staging modalities include computed tomography (CT) of the chest and abdomen, and endoscopic ultrasound (EUS). The overall tumor depth staging accuracy of EUS is 85% to 90%, as compared with 50% to 80% for CT; the accuracy of regional nodal staging is 70% to 80% for EUS and 50% to 70% for CT.[10][11] EUS-guided fine-needle aspiration (FNA) for lymph node staging is under prospective evaluation; one retrospective series reported a 93% sensitivity and 100% specificity of regional nodal staging with EUS-FNA.[12] Thoracoscopy and laparoscopy have been used in esophageal cancer staging at some surgical centers.[13][14][15] An intergroup trial (CALGB-9380) reported an increase in positive lymph node detection to 56% of 107 evaluable patients using thoracoscopy/laparoscopy, from 41% (using noninvasive staging tests, e.g., CT, magnetic resonance imaging, EUS) with no major complications or deaths.[16] Noninvasive positron emission tomography using the radiolabeled glucose analog 18-F-fluorodeoxy-D-glucose for preoperative staging of esophageal cancer is under clinical evaluation and may be useful in detecting stage IV disease.[17][18][19][20]

Gastrointestinal stromal tumors can occur in the esophagus and are usually benign. (Refer to the PDQ summary on Adult Soft Tissue Sarcoma Treatment for more information.)

References:

1. American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online. Last accessed January 6, 2010.

2. Devesa SS, Blot WJ, Fraumeni JF Jr: Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83 (10): 2049-53, 1998.  

3. Blot WJ, McLaughlin JK: The changing epidemiology of esophageal cancer. Semin Oncol 26 (5 Suppl 15): 2-8, 1999.  

4. Lagergren J, Bergström R, Lindgren A, et al.: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340 (11): 825-31, 1999.  

5. Tietjen TG, Pasricha PJ, Kalloo AN: Management of malignant esophageal stricture with esophageal dilation and esophageal stents. Gastrointest Endosc Clin N Am 4 (4): 851-62, 1994.  

6. 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. Gastrointest Endosc 42 (6): 507-12, 1995.  

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

8. Heier SK, Heier LM: Tissue sensitizers. Gastrointest Endosc Clin N Am 4 (2): 327-52, 1994.  

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

10. Ziegler K, Sanft C, Zeitz M, et al.: Evaluation of endosonography in TN staging of oesophageal cancer. Gut 32 (1): 16-20, 1991.  

11. Tio TL, Coene PP, den Hartog Jager FC, et al.: Preoperative TNM classification of esophageal carcinoma by endosonography. Hepatogastroenterology 37 (4): 376-81, 1990.  

12. Vazquez-Sequeiros E, Norton ID, Clain JE, et al.: Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma. Gastrointest Endosc 53 (7): 751-7, 2001.  

13. Bonavina L, Incarbone R, Lattuada E, et al.: Preoperative laparoscopy in management of patients with carcinoma of the esophagus and of the esophagogastric junction. J Surg Oncol 65 (3): 171-4, 1997.  

14. Sugarbaker DJ, Jaklitsch MT, Liptay MJ: Thoracoscopic staging and surgical therapy for esophageal cancer. Chest 107 (6 Suppl): 218S-223S, 1995.  

15. Luketich JD, Schauer P, Landreneau R, et al.: Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer. J Thorac Cardiovasc Surg 114 (5): 817-21; discussion 821-3, 1997.  

16. Krasna MJ, Reed CE, Nedzwiecki D, et al.: CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer. Ann Thorac Surg 71 (4): 1073-9, 2001.  

17. Flamen P, Lerut A, Van Cutsem E, et al.: Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 18 (18): 3202-10, 2000.  

18. Flamen P, Van Cutsem E, Lerut A, et al.: Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer. Ann Oncol 13 (3): 361-8, 2002.  

19. Weber WA, Ott K, Becker K, et al.: Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 19 (12): 3058-65, 2001.  

20. van Westreenen HL, Westerterp M, Bossuyt PM, et al.: Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer. J Clin Oncol 22 (18): 3805-12, 2004.  

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Cellular Classification

Fewer than 50% of esophageal cancers are squamous cell carcinomas. Adenocarcinomas, typically arising in Barrett esophagus, account for at least 50% of malignant lesions, and the incidence of this histology appears to be rising. Barrett 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.
• Metaplastic intestinal epithelium with typical goblet cells.

Dysplasia is particularly likely to develop in the intestinal type mucosa.

Gastrointestinal stromal tumors can occur in the esophagus and are usually benign. (Refer to the PDQ summary on Adult Soft Tissue Sarcoma Treatment for more information.)

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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 the midthoracic esophagus, use only M1b because these tumors with metastases in nonregional lymph nodes have equally poor prognoses as do those with metastases 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 cell carcinomas of the upper third and middle third 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 caused by 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. 6th ed. New York, NY: Springer, 2002, pp 91-8.  

2. Iizuka T, Isono K, Kakegawa T, et al.: Parameters linked to ten-year survival in Japan of resected esophageal carcinoma. Japanese Committee for Registration of Esophageal Carcinoma Cases. Chest 96 (5): 1005-11, 1989.  

3. Korst RJ, Rusch VW, Venkatraman E, et al.: Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg 115 (3): 660-69; discussion 669-70, 1998.  

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Treatment Option Overview

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The prevalence of Barrett metaplasia in adenocarcinoma of the esophagus suggests that Barrett esophagus is a premalignant condition. Strong consideration should be given to resection in patients with high-grade dysplasia in the setting of Barrett metaplasia. Endoscopic surveillance of patients with Barrett 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 (e.g., dysphagia, in most 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.[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 years were compared to their younger peers.[3][Level of evidence: 3iiA, 3iiB] All of the patients in this series were selected for surgery on the basis of potential operative risk. Age alone should not determine therapy for patients with potentially resectable disease.

The optimal surgical procedure is controversial. One approach advocates transhiatal esophagectomy with anastomosis of the stomach to the cervical esophagus. A second approach advocates 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. One study concluded that transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy; however, median overall disease-free and quality-adjusted survival did not differ significantly.[4] Similarly, no differences in long-term quality of life (QOL) using validated QOL instruments have been reported.[5] In patients with partial esophageal obstruction, dysphagia may, at times, be relieved by placement of an expandable metallic stent [6] or by radiation therapy if the patient has disseminated disease or is not a candidate for surgery. Alternative methods of relieving dysphagia have been reported, including laser therapy and electrocoagulation to destroy intraluminal tumor.[7][8][9][10]

Surgical treatment of resectable esophageal cancers results in 5-year survival rates of 5% to 30%, with higher survival rates in patients with early-stage cancers. This is associated with a less than 10% operative mortality rate.[11] In an attempt to avoid this perioperative mortality and to relieve dysphagia, definitive radiation therapy in combination with chemotherapy has been studied. An Intergroup randomized trial, Radiation Therapy Oncology Group known as RTOG-8501, of chemotherapy and radiation therapy versus radiation therapy alone resulted in an improvement in 5-year survival for the combined modality group (27% vs. 0%).[12][Level of evidence: 1iiA] An eight-year follow-up of this trial demonstrated an overall survival (OS) rate of 22% for patients receiving chemoradiation therapy.[12] An Eastern Cooperative Oncology Group trial (EST-1282) of 135 patients showed that chemotherapy plus radiation provided a better 2-year survival rate than radiation therapy alone,[13] which was similar to that shown in the Intergroup trial.[12][Level of evidence: 1iiA] In an attempt to improve upon the results of RTOG-8501, Intergroup-0123 (RTOG-9405) randomly assigned 236 patients with localized esophageal tumors to chemoradiation with high-dose radiation therapy (64.8 Gy) and four monthly cycles of fluorouracil (5-FU) and cisplatin versus conventional-dose radiation therapy (50.4 Gy) and the same chemotherapy schedule.[14] Although originally designed to accrue 298 patients, this trial was closed in 1999 after a planned interim analysis showed that it was statistically unlikely that there would be any advantage to using high-dose radiation. At 2 years' median follow-up, no statistical differences were observed between the high-dose and conventional-dose radiation therapy arms in median survival (13 months vs. 18 months), 2-year survival (31% vs. 40%), or local/regional failures (56% vs. 52%).[14][Level of evidence: 1iiA]

Phase III trials have compared preoperative concurrent chemoradiation therapy to surgery alone for patients with esophageal cancer.[15][16][17][18][Level of evidence: 1iiA] A multicenter prospective randomized trial in which preoperative combined chemotherapy (i.e., cisplatin) and radiation therapy (37 Gy in 3.7 Gy fractions) followed by surgery was compared to surgery alone in patients with squamous cell carcinoma showed no improvement in OS and a significantly higher postoperative mortality (12% vs. 4%) in the combined modality arm.[15] In patients with adenocarcinoma of the esophagus, a single-institution phase III trial demonstrated a modest survival benefit (16 months vs. 11 months) for patients treated with induction chemoradiation therapy consisting of 5-FU, cisplatin, and 40 Gy (2.67 Gy fractions) plus surgery over resection alone.[16] A subsequent single-institution trial randomly assigned patients (75% with adenocarcinoma) to 5-FU, cisplatin, vinblastine, and radiation therapy (1.5 Gy twice daily to a total of 45 Gy) plus resection versus esophagectomy alone.[17] At a median follow-up of more than 8 years, there was no significant difference between the surgery alone and combined modality therapy with respect to median survival (17.6 months vs. 16.9 months), OS (16% vs. 30% at 3 years), or disease-free survival (16% vs. 28% at 3 years). An Intergroup trial (CALGB-9781) planned to randomly assign 475 patients with resectable squamous cell or adenocarcinoma of the thoracic esophagus to treatment with preoperative chemoradiation therapy (5-FU, cisplatin, and 50.4 Gy) followed by esophagectomy and nodal dissection or surgery alone.[18][Level of evidence: 1iiA] The trial was closed as a result of poor patient accrual; however, the results of the 56 enrolled patients, with a median follow-up of 6 years, were reported. The median survival was 4.48 years (95% confidence interval [CI], 2.4 years to not estimable) for trimodality therapy versus 1.79 years (95% CI, 1.41–2.59 years) for surgery alone (P = .002), with 5-year OS of 39% (95% CI, 21%–57%) versus 16% (95% CI, 5%–33%) for trimodality therapy versus surgery alone. On the basis of the results of these randomized trials, the optimal therapy for stages IIB, III, and IVA esophageal cancer remains to be defined, but surgery alone appears to be increasingly inadequate.

A phase III German trial also compared induction chemotherapy (three courses of bolus 5-FU, leucovorin, etoposide, and cisplatin) followed by chemoradiation therapy (cisplatin, etoposide, and 40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiation therapy (at least 65 Gy) without surgery (arm B) for patients with T3 or T4 squamous cell carcinoma of the esophagus.[19][Level of evidence: 1iiA] OS was the primary outcome. The analysis of 172 eligible, randomly assigned patients showed that OS at 2 years was not statistically significantly different between the two treatment groups (arm A: 39.9%; 95% CI, 29.4%–50.4%; arm B: 35.4%; 95% CI, 25.2%–45.6%; log-rank test for equivalence with 0.15, P < .007). Local progression-free survival (PFS) was higher in the surgery group (2-year PFS, 64.3%; 95% CI, 52.1%–76.5%) than in the chemoradiation therapy group (2-year PFS, 40.7%; 95% CI, 28.9%–52.5%; hazard ratio for arm B vs. arm A, 2.1; 95% CI, 1.3–3.5; P < .003). Treatment-related mortality was higher in the surgery group compared with the chemoradiation therapy group (12.8% vs. 3.5%, respectively; P < .03).

The effects of preoperative chemotherapy have been evaluated in two randomized trials, including the NCT00525785 trial.[20][21][Level of evidence: 1iiA]. An Intergroup trial randomly assigned 440 patients with local and operable esophageal cancer of any cell type to three cycles of preoperative 5-FU and cisplatin followed by surgery and two additional cycles of chemotherapy versus surgery alone. After a median follow-up of 55 months, there were no significant differences between the chemotherapy/surgery and surgery-alone groups in median survival (14.9 months and 16.1 months, respectively) or 2-year survival (35% and 37%, respectively). The addition of chemotherapy did not increase the morbidity associated with surgery. The Medical Research Council Oesophageal Cancer Working Party randomly assigned 802 patients with resectable esophageal cancer also of any cell type to two cycles of preoperative 5-FU and cisplatin followed by surgery versus surgery alone. At a median follow-up of 37 months, median survival was significantly improved in the preoperative chemotherapy arm (16.8 months vs. 13.3 months with surgery alone; difference 3.5 months; 95% CI, 1–6.5 months), as was 2-year OS (43% and 34% respectively; difference 9%; 95% CI, 3–14 months). The interpretation of the results from both of these trials is challenging because T or N staging was not reported and prerandomization and radiation could be offered at the discretion of the treating oncologist. Therefore, preoperative chemotherapy should still be considered under clinical evaluation.

Two randomized trials have shown no significant OS benefit for postoperative radiation therapy over surgery alone.[22][23][Level of evidence: 1iiA] All newly diagnosed patients should be considered candidates for therapies and clinical trials comparing various treatment modalities. Information about ongoing clinical trials is available from the NCI Web site.

Special attention to nutritional support is indicated in any patient undergoing treatment of esophageal cancer. (Refer to the PDQ summary on Nutrition in Cancer Care for more information.)

References:

1. Lerut T, Coosemans W, Van Raemdonck D, et al.: Surgical treatment of Barrett's carcinoma. Correlations between morphologic findings and prognosis. J Thorac Cardiovasc Surg 107 (4): 1059-65; discussion 1065-6, 1994.  

2. Ginsberg RJ: Cancer treatment in the elderly. J Am Coll Surg 187 (4): 427-8, 1998.  

3. Ellis FH Jr, Williamson WA, Heatley GJ: Cancer of the esophagus and cardia: does age influence treatment selection and surgical outcomes? J Am Coll Surg 187 (4): 345-51, 1998.  

4. Hulscher JB, van Sandick JW, de Boer AG, et al.: Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 347 (21): 1662-9, 2002.  

5. de Boer AG, van Lanschot JJ, van Sandick JW, et al.: Quality of life after transhiatal compared with extended transthoracic resection for adenocarcinoma of the esophagus. J Clin Oncol 22 (20): 4202-8, 2004.  

6. Saxon RR, Morrison KE, Lakin PC, et al.: Malignant esophageal obstruction and esophagorespiratory fistula: palliation with a polyethylene-covered Z-stent. Radiology 202 (2): 349-54, 1997.  

7. Campbell WR Jr, Taylor SA, Pierce GE, et al.: Therapeutic alternatives in patients with esophageal cancer. Am J Surg 150 (6): 665-8, 1985.  

8. Mellow MH, Pinkas H: Endoscopic therapy for esophageal carcinoma with Nd:YAG laser: prospective evaluation of efficacy, complications, and survival. Gastrointest Endosc 30 (6): 334-9, 1984.  

9. Fleischer D, Sivak MV Jr: Endoscopic Nd:YAG laser therapy as palliation for esophagogastric cancer. Parameters affecting initial outcome. Gastroenterology 89 (4): 827-31, 1985.  

10. 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): 1969-72, 1987.  

11. Kelsen DP, Bains M, Burt M: Neoadjuvant chemotherapy and surgery of cancer of the esophagus. Semin Surg Oncol 6 (5): 268-73, 1990.  

12. 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). Radiation Therapy Oncology Group. JAMA 281 (17): 1623-7, 1999.  

13. 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. Int J Radiat Oncol Biol Phys 42 (2): 269-76, 1998.  

14. Minsky BD, Pajak TF, Ginsberg RJ, et al.: INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 20 (5): 1167-74, 2002.  

15. Bosset JF, Gignoux M, Triboulet JP, et al.: Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 337 (3): 161-7, 1997.  

16. Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335 (7): 462-7, 1996.  

17. Urba SG, Orringer MB, Turrisi A, et al.: Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 19 (2): 305-13, 2001.  

18. Tepper J, Krasna MJ, Niedzwiecki D, et al.: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26 (7): 1086-92, 2008.  

19. Stahl M, Stuschke M, Lehmann N, et al.: Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23 (10): 2310-7, 2005.  

20. Kelsen DP, Ginsberg R, Pajak TF, et al.: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 339 (27): 1979-84, 1998.  

21. Medical Research Council Oesophageal Cancer Working Group.: Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359 (9319): 1727-33, 2002.  

22. Ténière P, Hay JM, Fingerhut A, et al.: Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet 173 (2): 123-30, 1991.  

23. Fok M, Sham JS, Choy D, et al.: Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery 113 (2): 138-47, 1993.  

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Stage 0 Esophageal Cancer

Stage 0 squamous esophageal cancer is rarely seen in the United States, but surgery has been used for this stage of cancer.[1][2]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage 0 esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Rusch VW, Levine DS, Haggitt R, et al.: The management of high grade dysplasia and early cancer in Barrett's esophagus. A multidisciplinary problem. Cancer 74 (4): 1225-9, 1994.  

2. Heitmiller RF, Redmond M, Hamilton SR: Barrett's esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy. Ann Surg 224 (1): 66-71, 1996.  

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Stage I Esophageal Cancer

Standard treatment option:  

• Surgery.

Treatment options under clinical evaluation:  

• Clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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Stage II Esophageal Cancer

Standard treatment options:  

1. Surgery.
2. Chemoradiation.

Treatment option under clinical evaluation:  

• Chemoradiation with subsequent surgery, such as in the RTOG-8501 trial.[1][2][3]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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). Radiation Therapy Oncology Group. JAMA 281 (17): 1623-7, 1999.  

2. Herskovic A, Al-Sarraf M: Combination of 5-Fluorouracil and Radiation in Esophageal Cancer. Semin Radiat Oncol 7 (4): 283-290, 1997.  

3. Ajani JA, Komaki R, Putnam JB, et al.: A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction. Cancer 92 (2): 279-86, 2001.  

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Stage III Esophageal Cancer

Standard treatment options:  

1. Surgical resection of T3 lesions.
2. Chemoradiation.

Treatment options under clinical evaluation:  

• Chemoradiation with subsequent surgery, such as in the RTOG-8501 trial.[1][2]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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). Radiation Therapy Oncology Group. JAMA 281 (17): 1623-7, 1999.  

2. Herskovic A, Al-Sarraf M: Combination of 5-Fluorouracil and Radiation in Esophageal Cancer. Semin Radiat Oncol 7 (4): 283-290, 1997.  

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Stage IV Esophageal Cancer

At diagnosis, approximately 50% of patients with esophageal cancer will have metastatic disease and will be candidates for palliative therapy.[1]

Standard treatment options:  

1. Endoscopic-placed stents to provide palliation of dysphagia.[2]
2. Radiation therapy with or without intraluminal intubation and dilation.
3. Intraluminal brachytherapy to provide palliation of dysphagia.[3][4]
4. Nd:YAG endoluminal tumor destruction or electrocoagulation.[5]
5. Chemotherapy has provided partial responses for patients with metastatic distal esophageal adenocarcinomas.[6][7][8]

Treatment options under clinical evaluation:  

Many agents are active in esophageal cancer. Objective response rates of 30% to 60% and median survivals of less than 1 year are commonly reported with platinum-based combination regimens with fluorouracil, taxanes, topoisomerase inhibitors, hydroxyurea, or vinorelbine.[1][8][9]

• Clinical trials evaluating single-agent or combination chemotherapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Enzinger PC, Ilson DH, Kelsen DP: Chemotherapy in esophageal cancer. Semin Oncol 26 (5 Suppl 15): 12-20, 1999.  

2. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.  

3. Sur RK, Levin CV, Donde B, et al.: Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study. Int J Radiat Oncol Biol Phys 53 (1): 127-33, 2002.  

4. Gaspar LE, Nag S, Herskovic A, et al.: American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA. Int J Radiat Oncol Biol Phys 38 (1): 127-32, 1997.  

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

6. Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.  

7. Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.  

8. Taïeb J, Artru P, Baujat B, et al.: Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer. Eur J Cancer 38 (5): 661-6, 2002.  

9. Conroy T, Etienne PL, Adenis A, et al.: Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival. Ann Oncol 13 (5): 721-9, 2002.  

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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.

Standard treatment options:  

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

Treatment options under clinical evaluation:  

• Clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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More Information

About PDQ  

• PDQ® - NCI's Comprehensive Cancer Database.
  • Full description of the NCI PDQ database.
   

Additional PDQ Summaries  

• PDQ® Cancer Information Summaries: Adult Treatment
  • Treatment options for adult cancers.
   
• PDQ® Cancer Information Summaries: Pediatric Treatment
  • Treatment options for childhood cancers.
   
• PDQ® Cancer Information Summaries: Supportive and Palliative Care
  • Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
   
• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
  • Tests or procedures that detect specific types of cancer.
   
• PDQ® Cancer Information Summaries: Prevention
  • Risk factors and methods to increase chances of preventing specific types of cancer.
   
• PDQ® Cancer Information Summaries: Genetics
  • Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
   
• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
  • Information about complementary and alternative forms of treatment for patients with cancer.
   

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).

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This information is provided by the National Cancer Institute.

This information was last updated on July 2, 2009.