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Editors

JoonasH.Kauppila
OlliHelminen

Oesophageal Cancer

Essentials

  • Dysphagia and weight loss are the most common symptoms of oesophageal cancer. Early-stage cancers are often asymptomatic.
  • Gastroscopy is the primary examination.
  • Modern endoscopic surgery and cytostatic treatment have greatly improved the prognosis.

Prevalence and prognosis

  • Globally, oesophageal cancer is the 11th most common type of cancer and the 6th most common cause of death in cancer.
  • The mean age at onset is 68 years but the disease is sometimes seen in patients younger than 50.
  • Oesophageal adenocarcinoma is increasing significantly in western countries, whereas the incidence of squamous cell carcinoma is decreasing.
  • Of patients with oesophageal cancer, 17% survive 5 years from diagnosis.
  • Of those treated surgically, approximately 60% are alive after 5 years.

Aetiology

Histology

  • Adenocarcinoma
    • Typically situated at the border of the oesophagus and the stomach or low in the oesophagus.
    • An adenocarcinoma may develop in Barrett's columnar epithelium seen in association with GORD.
  • Squamous cell carcinoma
    • Develops through squamous dysplasia.
    • May develop in any part of the oesophagus.
  • Rare types of tumours include GISTs, melanoma and mesenchymal tumours.

Symptoms and findings

  • Early oesophageal cancer is often asymptomatic. A tumour obstructing the lumen will cause dysphagia, which is by far the most common symptom reported by patients.
  • Warning symptoms
    • Heartburn not responding to treatment
    • Dysphagia
    • Unintentional weight loss
    • Nausea and vomiting
    • Black stools, melaena, anaemia

Diagnosis and staging

  • Gastroscopy and biopsies
    • Whenever there are warning symptoms, and for patients over 55 with new upper abdominal symptoms Gastroscopy
  • PVK (basic blood count) to exclude anaemia
  • Whole-body CT for staging
    • Surgical treatment is suitable for less than 40% of patients at the time of diagnosis.
  • Whole-body PET-CT is performed before any surgery to detect any lymph nodes or metastases
  • To be done as necessary:
    • Endoscopic ultrasonography: depth of tumour invasion (T category)
    • Bronchoscopy: infiltration of the respiratory tract
    • Laparoscopy: spread in the abdominal cavity

Treatment

  • The lines of treatment of oesophageal cancer are assessed at a multiprofessional meeting.

Endoscopic treatment

  • Less than 10% of oesophageal cancers can be treated endoscopically.
  • High-grade dysplasias and incipient cancers can be treated by endoscopic submucosal dissection (ESD).
  • In association with the treatment of dysplasia or incipient cancer, Barrett's epithelium is treated by radiofrequency ablation.
  • Local recurrence is possible and is monitored by endoscopies.

Surgical treatment with a curative aim

  • Oesophagectomy is a major procedure often involving complications.
    • Surgical treatment cannot be used if the patient is in a poor condition.
    • Fitness for surgery can be assessed by a simple stair test. If the patient is capable of climbing 4 flights of stairs, their physical condition is sufficient for surgery.
  • Oesophagectomy is usually done by a mini-invasive endoscopic procedure, today often with robotic assistance.
    • The new oesophagus is usually made from the patient's stomach formed into a tube; the large and small intestine can also be used as spare parts.
  • If there is an upper oesophageal tumour, laryngectomy may sometimes be necessary.
  • Soft tissue and lymph node areas surrounding the oesophagus and the stomach are removed with the tumour.
  • About half of patients have postsurgical complications. The 90-day mortality rate after surgery is about 6%.
  • Quality of life will typically be affected for several months to a year after surgery.

Oncological treatment combined with curative surgery

  • Neoadjuvant therapy refers to radiotherapy and/or cytostatic therapy administered before surgery. Neoadjuvant therapy improves the prognosis of oesophageal cancer considerably.
  • Preoperative cytostatic treatment
    • To the extent possible, it is used for all but incipient disease.
    • A combination of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) is the primary choice for patients who are in a good general condition.
    • Another useful option is the combination of epirubicin, a platinum-based cytostatic drug, and fluorouracil or capecitabine.
    • The most typical symptoms associated with the treatment include nausea, neutropenia and neuropathy.
  • Preoperative chemoradiotherapy
    • Due to the sensitivity of the disease to radiation, this is the primary choice for squamous epithelium cancer of the oesophagus.
    • It can also be used for adenocarcinoma.
    • The most typical pattern is radiotherapy (41.4 Gy) using a combination of paclitaxel and carboplatin as the radiosensitizer.
  • Postoperative adjuvant therapy
    • Postoperative adjuvant therapy is given to
      • patients with adenocarcinoma who have been given preoperative cytostatic therapy (no chemoradiotherapy)
      • patients whose disease has in pathological assessment proved to be more widely spread than expected.
    • Immuno-oncological treatment is being developed for adjuvant therapy of oesophageal cancer.

Definitive chemoradiotherapy

  • Squamous cell carcinoma may potentially be cured by chemoradiotherapy alone; this is called definitive chemoradiotherapy.
  • Definitive chemoradiotherapy is the primary form of treatment for upper oesophageal squamous cell carcinoma.
  • Definitive chemoradiotherapy is a good option for the treatment of patients with squamous cell carcinoma who are poor candidates for surgical treatment.

Palliative treatment

  • In metastatic disease, life expectancy is about 3-4 months without treatment and 12 months with cytostatic therapy.
  • In HER2-positive disease, adding the HER2-antibody trastuzumab to the regimen prolongs life expectancy significantly.
  • Immuno-oncological treatment has proved useful for the treatment of metastatic oesophageal cancer.
  • Oesophageal obstruction is treated with endoscopic stenting.
  • Radiotherapy may be beneficial for treating haemorrhage from the tumour and pain from metastases.

Follow-up

  • So far, follow-up has not been shown to improve the prognosis.
  • For the first years after surgery, patients with oesophageal cancer should be monitored in specialized care.
  • In long-term follow-up, alleviation of symptoms and follow-up of the patient's nutritional status are of central importance.
  • Detection of recurrence
    • Endoscopic follow-up particularly after endoscopic treatment
    • Whole-body CT is commonly done 2 years after surgery even though the evidence of its benefit is scarce.
  • Alleviation of symptoms and improvement of quality of life
    • Treatment of gastro-oesophageal reflux by giving lifestyle guidance and proton pump inhibitors Gastro-Oesophageal Reflux Disease
    • Alleviation of gastroparesis by dietary treatment and metoclopramide
    • Detection of anastomosis stricture and its treatment by endoscopic dilation
    • Alleviation of dumping symptoms by lifestyle guidance and medication
  • Follow-up and maintenance of good nutritional status
    • Weight, basic blood count with platelet count, sodium, potassium, creatinine, plasma albumin, plasma glucose usually every 12 months to assess nutritional status
    • Assessment by a therapeutic dietitian on postsurgical checkup visits and subsequently, as necessary
    • Vitamin B12, calcium + vitamin D, iron and multivitamin replacement therapy for life as instructed by specialized care

    References

    • Obermannová R, Smyth EC, ESMO Guidelines Committee. Electronic address: [email protected]. Reply to the Letter to the Editor 'Neoadjuvant radiochemotherapy and perioperative chemotherapy does not represent a standard at same priority level for oesophageal adenocarcinomas (in regard to "Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up")' by Cellini et al. Ann Oncol 2023;34(6):554-555 [PubMed]
    • Deboever N, Jones CM, Yamashita K, et al. Advances in diagnosis and management of cancer of the esophagus. BMJ 2024;385():e074962 [PubMed]

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