Oesophageal cancer

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Clinical oncology for students > Oesophageal cancer


Epidemiology

The predominant histologies of oesophageal carcinoma are squamous cell carcinoma (SCC) and adenocarcinoma. In 2008 the incidence of oesophageal cancer was ~3.4 per 100,000 people/year with a mortality rate of 3% of cancer deaths.[1] Men account for 75% of cases. SCC incidence appears likely to fall in the future as smoking rates decrease. The incidence of adenocarcinoma, previously rare, has increased in and in men it is now more common than SCC.[2]


Risk factors

Squamous cell carcinoma is strongly associated with smoking and heavy alcohol intake and accounts for ~90% of all cases in Australia. The consumption of very hot drinks in some countries is associated with SCC. Adenocarcinoma is associated with conditions that cause Barrett’s oesophagus which include obesity and gastro-oesophageal reflux. Smoking contributes to about 40% of cases.[3]


Cancer biology

SCC may arise de novo or within an area of squamous cell carcinoma in situ[3], often in the upper oesophagus.

Adenocarcinoma of the oesophagus often arises from Barrett’s oesophagus. This refers to metaplasia of the lower oesophagus, with replacement of the stratified squamous epithelium with a glandular epithelium. Transformation to intraepithelial neoplasia may occur within Barrett's oesophagus as a precursor to invasive malignancy[3]. Local invasion through the oesophageal wall into neighboring thoracic structures is common, as is spread to regional nodes. Haematogenous spread to the liver is common.[3]


Clinical presentation

Oesophageal cancer commonly causes progressive dysphagia, weight loss and subsequent malnutrition. Tracheooesophageal fistula causing aspiration can also occur. Distant metastases can cause bone and/or abdominal pain and jaundice from liver involvement.[3]


Diagnosis and staging

Histopathological diagnosis is obtained through gastroscopy. Endoscopic ultrasound (for locoregional staging) and PET/CT scan (for regional and distant staging) are used.[4]

Oesophageal cancer is staged using the TNM system:[5]

  • Stage I tumours are minimally invasive and/or low grade.
  • Stage II tumours invade into or through the muscular coat of the oesophagus, or are minimally invasive with 1-2 lymph node metastases.
  • Stage III tumours invade adjacent structures or have numerous regional nodal metastases.
  • Stage IV tumours have metastasised to distant sites.


Prognosis

Five-year survival of patients with localised (or nodal) disease are 25% and distant metastases 4%.


Management

Stage I disease

Minimally invasive oesophageal cancers can be managed with surgical excision alone. Disease that more extensively invades the submucosa or with lymph node metastases is managed as per Stage II disease.


Stage II-III disease

Patients with disease that invades the muscularis propria or beyond, or those with lymph node metastases, have average survival rates at 5 years of less than 20% with single modality therapy.[6][7] Combination chemoradiotherapy without surgery has demonstrated superiority to radiotherapy alone[8] and multiple trials have examined the combination of chemoradiotherapy with surgery. Meta-analysis of trimodality studies has demonstrated improvements in absolute survival advantage of 8.7% at two years[9] over surgery alone. Adenocarcinoma that arises in the vicinity of the gastro-oesophageal junction may be treated similarly to gastric cancer with neoadjuvant and adjuvant chemotherapy.[10]


Stage IV disease

Patients with distant metastases typically have a dismal prognosis. Palliative measures include endoscopic dilatation, laser therapy, stenting the primary lesion or local external beam radiotherapy. Systemic therapy is typically with the combination of a fluropyrimidine and platinum agent with improvements in quality of life and survival improvements. About 20% of patients with gastroeosphageal adenocarcinoma are HER2 positive and in the advanced disease setting the monoclonal antibody trastuzumab has shown to improve survival when added to chemotherapy.


Supportive measures

In addition to local therapies aimed at maintaining swallowing, attention needs to be paid to nutrition including enteral feeding and dietician review. The involvement of palliative care services is important.


Follow-up

Patients with oesophageal cancer should been seen regularly to monitor for complications of disease progression or treatment.


Screening and prevention

Population screening has no proven benefit. Patients with Barrett's oesophagus may benefit from routine surveillance, although only a limited number of patients progress to invasive cancer.[11]


Case examples

Case 1

Mrs J, a 55 year old woman otherwise in excellent health, presents with a 6-week history of progressive dysphagia to solids.

  • What initial investigation is warranted?

Gastroscopy confirms a SCC of the upper third of the oesophagus.

  • What staging investigations would you perform?

Staging indicates invasion through the muscular wall of the oesophagus with no regional nodal metastases. What treatment recommendations would you make?


Case 2

Mr B is a 75 year old man who has been diagnosed with dysphagia, distal oesophageal cancer and liver metastases.

  • How would you manage the primary tumour site?
  • How would you approach systemic treatment in this man?

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Cancer incidence and mortality worldwide: GLOBOCAN 2008 v2.0. Lyon, France: International Agency for Research; 2010 Jan 1. Report No.: IARC CancerBase No. 10. Available from: http://globocan.iarc.fr.
  2. Stavrou E, Baker D, McElroy H, Bishop JF. Oesophageal cancer in New South Wales. Sydney: Cancer Institute NSW; 2009 Feb [cited 2014 May 20] Available from: http://www.cancerinstitute.org.au/media/25194/2009-02_oesophageal_cancer_in_nsw.pdf.
  3. 3.0 3.1 3.2 3.3 3.4 Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. Lyon, France: International Agency for Research on Cancer; 2000 [cited 2014 May 20] Available from: http://w2.iarc.fr/en/publications/pdfs-online/pat-gen/bb2/BB2.pdf.
  4. van Vliet EP, Heijenbrok-Kal MH, Hunink MG, Kuipers EJ, Siersema PD. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer 2008 Feb 12;98(3):547-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18212745.
  5. Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging handbook. New York: Springer; 2010 [cited 2014 May 20].
  6. Rice TW, Rusch VW, Apperson-Hansen C, Allen MS, Chen LQ, Hunter JG, et al. Worldwide esophageal cancer collaboration. Dis Esophagus 2009;22(1):1-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19196264.
  7. Earlam R, Cunha-Melo JR. Oesophogeal squamous cell carcinoms: II. A critical view of radiotherapy. Br J Surg 1980 Jul;67(7):457-61 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6158354.
  8. Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992 Jun 11;326(24):1593-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1584260.
  9. Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011 Jul;12(7):681-92 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21684205.
  10. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006 Jul 6;355(1):11-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16822992.
  11. Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, et al. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011 Jul 6;103(13):1049-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21680910.