Elsevier

The Lancet

Volume 390, Issue 10110, 25 November–1 December 2017, Pages 2383-2396
The Lancet

Seminar
Oesophageal cancer

https://doi.org/10.1016/S0140-6736(17)31462-9Get rights and content

Summary

Oesophageal cancer is a clinically challenging disease that requires a multidisciplinary approach. Extensive treatment might be associated with a considerable decline in health-related quality of life and yet still a poor prognosis. In recent decades, prognosis has gradually improved in many countries. Endoscopic procedures have increasingly been used in the treatment of premalignant and early oesophageal tumours. Neoadjuvant therapy with chemotherapy or chemoradiotherapy has supplemented surgery as standard treatment of locally advanced oesophageal cancer. Surgery has become more standardised and centralised. Several therapeutic alternatives are available for palliative treatment. This Seminar aims to provide insights into the current clinical management, ongoing controversies, and future needs in oesophageal cancer.

Introduction

Oesophageal cancer is the ninth most common cancer and the sixth most common cause of cancer death globally.1 This cancer is associated with extensive treatment requirements, a considerable decline in health-related quality of life (HRQoL), and poor prognosis. Curative treatment typically includes chemotherapy or chemoradiotherapy followed by extensive surgery, often resulting in morbidity and persistent reductions in HRQoL.2 However, recent developments have improved prognosis and survivorship.

Section snippets

Clinical presentation, signs, and symptoms

Most patients seek medical attention following a period of progressive dysphagia and involuntary weight loss. Older men (aged ≥60 years) are over-represented in both main histological types—ie, oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. The mean male to female ratio is 3:1 for oesophageal squamous cell carcinoma and 6:1 for oesophageal adenocarcinoma, although this ratio varies considerably across geographical regions.3, 4 Many patients with oesophageal squamous cell

Incidence and prognosis

Globally, oesophageal squamous cell carcinoma is the most common histological subtype of oesophageal cancer, particularly in high-incidence areas of eastern Asia and in eastern and southern Africa.1, 5, 6 In the highest-risk region (the so-called oesophageal cancer belt) from northern Iran through Central Asia to north-central China, approximately 90% of patients with oesophageal cancer have oesophageal squamous cell carcinomas.1, 5, 6 Although the incidence of oesophageal squamous cell

Squamous cell carcinoma

The pathophysiological pathway of oesophageal squamous cell carcinoma is typically initiated by carcinogenic compounds in direct contact with the oesophageal mucosa. Mechanical injury (eg, from achalasia, radiation therapy, or from swallowing hot beverages or sodium hydroxide) increases susceptibility to carcinogenic compounds. The main risk factors for oesophageal squamous cell carcinoma are tobacco smoking (including swallowed toxins from cigarette smoke) and alcohol overconsumption,

Genetics

Developments in high-throughput genomic technologies have led to improved understanding of the molecular underpinnings of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. The Global Cancer Genome Atlas project characterised 164 oesophageal cancers using multiple platforms, and oesophageal squamous cell carcinoma and oesophageal adenocarcinoma had distinct profiles in copy number alterations, methylation patterns, and RNA and microRNA expression (table 1).25 In particular,

Diagnosis

The presence of oesophageal cancer is determined by endoscopy (figure 1) with biopsies for histopathological confirmation. Endoscopy also provides information about the tumour sublocation and local extent, and the presence and extent of Barrett's oesophagus. After the diagnosis is established, CT of the neck, chest, and abdomen to assess distant metastasis will guide whether treatment will follow a curative or palliative route.

Operability

Treatment recommendations are dependent on tumour stage and the

Treatment recommendations

Multidisciplinary assessment and determination of a treatment plan has been shown to improve clinical decision making in oesophageal cancer and should be mandatory.39, 40, 41 Ideally, the multidisciplinary team should have expertise in pathology, radiology, endoscopy, medical oncology, radiotherapy, surgery, nursing, dietetics, and other relevant specialists as needed (eg, laryngologists, physiotherapists, and social workers).42 Treatment plans depend on clinical tumour stage, subsite, and

Endoscopic treatment

Endoscopic techniques, mainly radiofrequency ablation, endoscopic mucosal resection, and endoscopic submucosal dissection, are increasingly used for the prevention and curative treatment of early oesophageal lesions.43, 44 Most research has examined Barrett's oesophagus and early oesophageal adenocarcinoma, but some studies45, 46 also support ablation therapies in early oesophageal squamous cell carcinomas. Endoscopic mucosal resection combined with radiofrequency ablation can successfully

Survivorship

Patients who have had oesophagectomy often have specific survivorship issues, including decreased HRQoL, eating difficulties and malnutrition, and poor long-term survival. A 2014 meta-analysis101 showed long-lasting deterioration in several HRQoL aspects, including social functioning, role functioning, and increased symptoms of fatigue, pain, cough, dry mouth, and reflux. Additionally, patients often experience major social and emotional changes, and might have an increased risk of developing

Patient selection

Most patients diagnosed with oesophageal cancer are not eligible for curative therapy or will develop tumour recurrence despite curatively intended treatment.56, 60, 61 Advanced tumour stage at diagnosis (eg, most T4 tumours [involving adjacent tissue surrounding the oesophagus] and M1 [tumour with distant metastasis]) indicates a requirement for palliative treatment. Little evidence exists about how to select patients for palliative regimen on the basis of other conditions, but selection

Endoscopic treatment

Although early tumours (T1) are not often identified, evaluating when endoscopic (organ-sparing) treatment can be recommended above surgical resection is important. More large-scale observational research and randomised controlled trials are needed to answer this question.

Oncological treatment

The potential advantage of neoadjuvant chemotherapy compared with chemoradiotherapy requires clarification. Both treatments are associated with tumour downstaging, but rates of complete tumour response are higher following

Outstanding research questions

Increased detection of premalignant lesions and early stage tumours would improve prognosis. However, general endoscopic screening might not be cost-effective or clinically feasible, or well tolerated by certain individuals. Future alternatives might include screening of carefully selected absolute high-risk individuals (with a combination of risk factors) in combination with the use of less invasive screening tools, such as cytosponge or breath tests,158, 159 although more research is needed

Search strategy and selection criteria

We searched PubMed, Cochrane Library, MEDLINE, and Embase databases for publications in English using the search terms “(o)esophageal” or “(o)esophagus” in combination with the terms “cancer” or “neoplasm” or “adenocarcinoma” or “squamous cell carcinoma”. We largely selected publications from the past 5 years. Review articles and book chapters are cited to provide readers with more details and more references than this Seminar has room for.

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