Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Oesophageal Cancer article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Carcinoma of the oesophagus is a common, aggressive tumour. Several histological types are seen, almost all of which are epithelial in origin. The vast majority of these tumours will be either squamous cell carcinoma (SCC) or adenocarcinoma (AC).
The incidence of AC and its precursor lesion, Barrett's oesophagus, has increased in Western populations over the past four decades; the incidence of SCC has declined in most parts of the world over the same period. SCC still accounts for the vast majority of all oesophageal cancer cases diagnosed worldwide each year.
Incidence rates in the UK are considerably higher than the EU average.
- Carcinoma of the oesophagus represents the 14th most common malignant tumour in the UK, and is the 8th most common cancer in the world.
- There are 9,200 people diagnosed with oesophageal cancer in the UK each year. It is more common in men than women. The gap is widest at age 25-29, when the age-specific incidence rate is 16 times lower in females than males. This difference narrows with unceasing age.
- It is more common in older people. In the UK, on average each year around 40 out of 100 (around 40%) of new cases are in people aged 75 and over. The peak age is 85-89 years. It is very rare in people younger than 40.
The incidence of oesophageal carcinoma varies considerably with geographical location, with high rates in China and Iran, where it has been directly linked to the preservation of food using nitrosamines. AC is seen more frequently in Caucasian populations, whereas SCC is more frequent in people of African descent. There is considerable geographical variation of lower oesophageal cancer within the UK, the reason for which is being investigated.
- The use of tobacco and alcohol are strong risk factors for both SCC and AC and have a synergistic effect in this respect for SCC and additive effect for AC. Cigarette smoking is associated with a 10-fold increase in risk for SCC and a 2- to 3-fold increase in risk for AC. The relative increase in risk caused by smoking remains high for AC, even after 20 years of giving up smoking, but reduces within five years for SCC .
- Barrett's oesophagus, which is a precursor of AC.
- Chronic inflammation and stasis from any cause increase the risk of oesophageal SCC - eg, strictures due to caustic injury or achalasia.
- Tylosis and Plummer-Vinson syndrome are also associated with an increased risk for SCC.
- Obesity has been linked with increased risk for AC but reduced risk for SCC. Obesity increases the risk of gastro-oesophageal reflux disease (GORD), in turn increasing the risk of Barrett's oesophagus. The relationship between obesity and the rise in AC has, however, been questioned. A review of the Connecticut Tumor Registry data between 1940-2007 showed that the increase in AC seen in the 1960s predated the rise in obesity by a decade. The authors of the review propounded that this may have been linked to a decrease in the incidence of Helicobacter pylori infection or environmental factors.
- One Japanese study showed a link between oesophageal cancer and tooth loss.
- A family history of hiatal hernia is a risk factor for oesophageal adenocarcinoma, and some people appear to have a genetic predisposition to developing types of gastro-oesophageal cancers.
- Anorexia and weight loss.
- Symptoms of gastrointestinal-related blood loss.
Oesophageal cancers often present late in the progress of the disease, because approximately 75% of the circumference of the oesophagus must be involved before symptoms of 'food sticking' are experienced. As a result, approximately half of the patients who present as a result of developing symptoms, will already have an unresectable tumour or distant metastases.
Symptoms and signs of oesophageal cancer which may cause a patient to present to a doctor include:
- Weight loss
- Loss of appetite
- Retrosternal pain
- Intractable hiccups
When to refer
Offer urgent, direct access upper gastrointestinal endoscopy (to be performed within two weeks) to assess for oesophageal cancer in people:
- With dysphagia; or
- Aged 55 and over with weight loss and any of the following:
- Upper abdominal pain
Consider non-urgent direct access upper gastrointestinal endoscopy to assess for oesophageal cancer in people with haematemesis.
Consider non‑urgent direct access upper gastrointestinal endoscopy to assess for oesophageal cancer in people aged 55 or over with:
- Treatment‑resistant dyspepsia; or
- Upper abdominal pain with low haemoglobin levels; or
- Raised platelet count with any of the following:
- Weight loss
- Upper abdominal pain; or
- Nausea or vomiting with any of the following:
- Weight loss
- Upper abdominal pain
- Oesophageal stricture from any cause.
- Compression of the oesophagus from external sources - eg, enlarged lymph glands or bronchial carcinoma.
- Gastric cancer.
- Intramural benign tumours - eg, leiomyoma.
- Metastatic tumours - most commonly from breast.
The initial investigation of a patient with symptoms suggestive of oesophageal carcinoma should include:
- FBC, U&E, LFT, glucose, CRP.
- Urgent endoscopy - with brushings and biopsy of any lesion seen.
Other possible staging investigations include:
- CXR - looking for evidence of metastases.
- Double-contrast barium swallow.
- CT/MRI scan of the chest and upper abdomen - for staging purposes.
- Fluorodeoxyglucose positron emission tomography (FDG-PET) scan - for accuracy of staging (combined with CT).
- Endoscopic ultrasound - increases accuracy of staging.
- Fine-needle aspiration - of any palpable cervical lymph node; ±
- Bronchoscopy - in high oesophageal tumours or if hoarseness or haemoptysis is present.
Chromoendoscopy (use of dyes), high-resolution endoscopy, spectroscopy, narrow band imaging (optical filter technology that improves the visibility of blood vessels) and autofluorescence (exploits the natural emission of light by biological tissues) are other modalities being investigated.
Assessment of patients diagnosed with gastro-oesophageal cancer
The National Institute for Health and Care Excellence (NICE) have issued guidance on the assessment and management of patients, once the diagnosis of cancer involving the gastro-oesophageal junction has been made. Such assessment helps differentiate those patients who should receive radical treatment from those who should receive palliative care.
- Offer 18F-FDG-PET/CT to people with oesophageal and gastro-oesophageal junctional tumours that are suitable for radical treatment (except for T1a tumours - a tumour that is larger than 1 mm but no larger than 5 mm).
- Do not offer endoscopic ultrasound only to distinguish between T2 to T3 tumours in people with oesophageal and gastro-oesophageal junctional tumours.
- Only offer endoscopic ultrasound to people with oesophageal and gastro‑oesophageal junctional cancer when it will help guide ongoing management.
- Only consider staging laparoscopy for people with oesophageal or gastro‑oesophageal junctional cancer when it will help guide ongoing management.
- Offer HER2 testing to people with metastatic oesophago-gastric adenocarcinoma. (Overexpression of the human epidermal growth factor receptor 2 gene (HER2) is recognised as a molecular abnormality associated with gastric and gastro-oesophageal cancer).
|T category||Depth of infiltration||N category||Regional lymph nodes|
|Tis||Carcinoma in situ||NX||Nodes cannot be assessed|
|T1||Invasion of lamina propria/submucosa||N0||No node spread|
|T2||Invasion of muscularis propria||N1||Regional node metastases|
|T3||Invasion of adventitia||M0||No distant spread|
|T4||Invasion of adjacent structures||M1||Distant metastases|
T1N0 oesophageal cancer
- Offer endoscopic mucosal resection for staging for people with suspected T1 oesophageal cancer.
- Offer endoscopic eradication of remaining Barrett's mucosa for people with T1aN0 oesophageal cancer.
- Offer radical resection for people with T1bN0 oesophageal adenocarcinoma if they are fit enough to have surgery. (T1b tumours are larger than 5 mm but no larger than 10 mm).
- Offer people with T1bN0 SCC of the oesophagus the choice of:
- Definitive chemoradiotherapy; or
- Surgical resection.
This choice should only be offered after the surgeon and oncologist have discussed the benefits, risks and treatment consequences of each option with the person and those who are important to them (as appropriate).
When performing a curative oesophagectomy for people with oesophageal cancer, consider two‑field lymph node dissection.
Localised oesophageal and gastro-oesophageal junctional adenocarcinoma
For people with localised oesophageal and gastro-oesophageal junctional adenocarcinoma (excluding T1N0 tumours) who are going to have surgical resection, offer a choice of:
- Chemotherapy, before or before and after surgery, or
- Chemoradiotherapy, before surgery.
The benefits, risks and treatment consequences of each option should be discussed with the person and those important to them (as appropriate):
- Encourage people to join relevant clinical trials, if available.
Squamous cell carcinoma of the oesophagus
Offer people with resectable non-metastatic SCC of the oesophagus the choice of:
- Radical chemoradiotherapy; or
- Chemoradiotherapy before surgical resection.
Discuss the benefits, risks and treatment consequences of each option with the person and those who are important to them (as appropriate).
Dr Sarah Jarvis, 22nd November 2021
Nivolumab for adjuvant treatment of resected oesophageal or gastro-oesophageal junction cancer
The most common treatment for oesophageal or gastro-oesophageal junction cancer is neoadjuvant chemoradiotherapy followed by surgery. Clinical trial evidence shows that after trimodal therapy (chemoradiotherapy and surgery), nivolumab increases disease-free survival and may increase life expectancy compared to standard care.
In addition to the guidance on unresectable oesophageal SCC below, NICE has now recommended nivolumab for adjuvant treatment of completely resected oesophageal or gastro-oesophageal junction cancer in adults who have residual disease after previous neoadjuvant chemoradiotherapy.
Many patients will present late in the disease process with unresectable disease. For this group of patients, the emphasis will be on palliation and symptom relief.
- Radiotherapy, brachytherapy, chemotherapy, electrocautery or plasma/laser ablation may be of use (primarily in reducing tumour bulk and bleeding).
- NICE offers detailed guidance on management for people with non-metastatic cancer, and first- and second-line treatment for people with metastatic cancer.
- Photodynamic therapy may also be used for palliation in advanced disease.
- Trastuzumab in combination with cisplatin/fluoropyrimidine should be considered for patients with HER2-positive oesophago-gastric junctional AC.
- NICE has issued new guidance on the use of nivolumab for treating unresectable advanced, recurrent or metastatic oesophageal SCC in adults after fluoropyrimidine and platinum-based therapy. Nivolumab is recommended, within its marketing authorisation, in these patients, but only if the company provides nivolumab according to the commercial arrangement.
- Stenting is a first-line option to assist swallowing.
- Nutritional status may be maintained by the use of liquid feeds, enteral nutrition or percutaneous endoscopic gastrotomy (PEG) tubes.
- Pain relief should be maintained at a level at which the patient experiences little, or no pain.
The patient's pre-operative status, comorbidity and presence or absence of metastases are strong predictors of outcome. The prognosis for oesophageal carcinoma varies depending on the stage at presentation. The overall five-year survival rate is 20-25% for all stages. Not surprisingly, lymph node involvement equates with a poorer prognosis. The survival rate for AC and SCC are the same.
A study of 1,085 patients who underwent oesophagectomy showed a 4% operative mortality rate and a 23% survival rate. For patients who had pre-operative chemoradiotherapy, the prognosis improved to 48%.
Reducing risk factors (obesity, smoking and alcohol) should help.
Earlier detection through screening and surveillance will improve survival rates. However, standard diagnostic tools (eg, endoscopy with biopsy) have several limitations as screening tools - including low negative predictive value and relatively high cost.
Further reading and references
Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up; European Society for Medical Oncology (2013)
Cheung WY, Liu G; Genetic variations in esophageal cancer risk and prognosis. Gastroenterol Clin North Am. 2009 Mar38(1):75-91, viii.
Bavi PP, Bu R, Uddin S, et al; MMP7 Polymorphisms - A new tool in molecular pathology to understand esophageal cancer. Saudi J Gastroenterol. 2011 Sep-Oct17(5):299-300. doi: 10.4103/1319-3767.84479.
Oesophageal Cancer Incidence; Cancer Research UK
Thrift AP; Global burden and epidemiology of Barrett oesophagus and oesophageal cancer. Nat Rev Gastroenterol Hepatol. 2021 Jun18(6):432-443. doi: 10.1038/s41575-021-00419-3. Epub 2021 Feb 18.
Tramontano AC, Nipp R, Mercaldo ND, et al; Survival Disparities by Race and Ethnicity in Early Esophageal Cancer. Dig Dis Sci. 2018 Nov63(11):2880-2888. doi: 10.1007/s10620-018-5238-6. Epub 2018 Aug 14.
Geographic variation in cancer of the lower oesophagus; National Cancer Intelligence Network, 2010
Risks and causes of oesophageal cancer; Cancer Research UK, 2011
Anderson LA, Watson RG, Murphy SJ, et al; Risk factors for Barrett's oesophagus and oesophageal adenocarcinoma: results from the FINBAR study. World J Gastroenterol. 2007 Mar 1413(10):1585-94.
Cook MB, Kamangar F, Whiteman DC, et al; Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium. J Natl Cancer Inst. 2010 Sep 8102(17):1344-53. doi: 10.1093/jnci/djq289. Epub 2010 Aug 17.
Wang QL, Xie SH, Li WT, et al; Smoking Cessation and Risk of Esophageal Cancer by Histological Type: Systematic Review and Meta-analysis. J Natl Cancer Inst. 2017 Dec 1109(12). pii: 4064131. doi: 10.1093/jnci/djx115.
Abrams JA, Sharaiha RZ, Gonsalves L, et al; Dating the rise of esophageal adenocarcinoma: analysis of Connecticut Tumor Registry data, 1940-2007. Cancer Epidemiol Biomarkers Prev. 2011 Jan20(1):183-6. Epub 2010 Dec 2.
Jiang X, Tseng CC, Bernstein L, et al; Family history of cancer and gastroesophageal disorders and risk of esophageal and gastric adenocarcinomas: a case-control study. BMC Cancer. 2014 Feb 414:60. doi: 10.1186/1471-2407-14-60.
Suspected cancer: recognition and referral; NICE guideline (2015 - last updated December 2021)
Smyth EC, Lagergren J, Fitzgerald RC, et al; Oesophageal cancer. Nat Rev Dis Primers. 2017 Jul 273:17048. doi: 10.1038/nrdp.2017.48.
Oesophago-gastric cancer: assessment and management in adults; NICE Guidance (Jan 2018)
Abrahao-Machado LF, Scapulatempo-Neto C; HER2 testing in gastric cancer: An update. World J Gastroenterol. 2016 May 2122(19):4619-25. doi: 10.3748/wjg.v22.i19.4619.
The stages of oesophageal cancer; Cancer Research UK
Nivolumab for adjuvant treatment of resected oesophageal or gastro-oesophageal junction cancer; NICE Technology appraisal guidance, November 2021
Guidelines for the management of oesophageal and gastric cancer; British Society of Gastroenterology (June 2011)
Hanna WC, Sudarshan M, Roberge D, et al; What is the optimal management of dysphagia in metastatic esophageal cancer? Curr Oncol. 2012 Apr19(2):e60-6. doi: 10.3747/co.19.892.
Palliative photodynamic therapy for advanced oesophageal cancer; NICE Interventional Procedure Guideline, January 2007
Trastuzumab for the treatment of HER2-positive metastatic gastric cancer; NICE Technology Appraisal Guideline, November 2010
Dubecz A, Gall I, Solymosi N, et al; Temporal trends in long-term survival and cure rates in esophageal cancer: a SEER database analysis. J Thorac Oncol. 2012 Feb7(2):443-7. doi: 10.1097/JTO.0b013e3182397751.