Elsevier

The Lancet

Volume 388, Issue 10060, 26 November–2 December 2016, Pages 2654-2664
The Lancet

Seminar
Gastric cancer

https://doi.org/10.1016/S0140-6736(16)30354-3Get rights and content

Summary

Gastric cancer is one of the leading causes of cancer-related death worldwide. Many patients have inoperable disease at diagnosis or have recurrent disease after resection with curative intent. Gastric cancer is separated anatomically into true gastric adenocarcinomas and gastro-oesophageal-junction adenocarcinomas, and histologically into diffuse and intestinal types. Gastric cancer should be treated by teams of experts from different disciplines. Surgery is the only curative treatment. For locally advanced disease, adjuvant or neoadjuvant therapy is usually implemented in combination with surgery. In metastatic disease, outcomes are poor, with median survival being around 1 year. Targeted therapies, such as trastuzumab, an antibody against HER2 (also known as ERBB2), and the VEGFR-2 antibody ramucirumab, have been introduced. In this Seminar, we present an update of the causes, classification, diagnosis, and treatment of gastric cancer.

Introduction

Gastric cancer is an important health problem, being the fourth most common cancer and the second leading cause of cancer death worldwide. More than 950 000 new diagnoses are made every year. An estimated 720 000 patients died from gastric cancer in 2012.1 Gastric cancer is separated anatomically into true gastric adenocarcinomas (non-cardia gastric cancers), of which there were 691 000 new cases in 2012, and gastro-oesophageal-junction adenocarcinomas (cardia gastric cancers), of which there were 260 000 new cases in that year.2 Despite a decline in incidence and mortality and despite important advances in the understanding of the epidemiology, pathology, molecular mechanisms, and therapeutic options and strategies, the burden remains high.

Gastric cancer is a main contributor to the global burden of disability-adjusted life-years from cancer in men and accounts for 20% of the total worldwide, following lung and liver cancers, which, respectively, account for 23% and 28%.3 The burden of gastric cancer remains very high in Asia, Latin America, and central and eastern Europe, whereas in North America and most western European countries, it is no longer a common cancer.4 Nevertheless, the decline in the incidence of gastric cancer has gradually lessened in some countries, particularly the USA. In other countries, such as France, mortality is predicted not to decrease further in the middle-aged population.4 This slowing of change is probably explained by long-term low and stable prevalence of Helicobacter pylori infection in these countries.4 By contrast, the incidence of gastro-oesophageal-junction adenocarcinomas is increasing sharply.5 In this Seminar we provide a comprehensive overview of the aetiology, pathological features, molecular pathogenesis, diagnosis, and treatment of gastric cancer.

Section snippets

Aetiology

H pylori infection is the most important cause of sporadic distal gastric cancer.6 During the chronic inflammation induced by H pylori infection and the subsequent carcinogenesis, various factors, including bacterial, host, and environmental factors, interact to facilitate damage repair. Altered cell proliferation, apoptosis, and some epigenetic modifications to the tumour suppressor genes might occur, which could eventually lead to inflammation-associated oncogenesis.7 Some patients with

Anatomical

Tumour classification on the basis of anatomical location is important because true gastric (non-cardia) and gastro-oesophageal-junction cancers (cardia) differ in terms of incidence, geographical distribution, causes, clinical disease course, and treatment. Gastro-oesophageal-junction cancers are widely categorised according to the Siewert classification:26 in true carcinomas of the cardia (Siewert type II) the tumour epicentre is located 1–2 cm below the gastro-oesophageal junction; in distal

Symptoms and diagnosis

Most patients with early-stage gastric cancer are asymptomatic and, therefore, diagnosis is frequently made when disease is at an advanced stage. The most common symptoms at diagnosis are anorexia, dyspepsia, weight loss, and abdominal pain. Patients with tumours at the gastro-oesophageal junction or proximal stomach might also present with dysphagia.

The diagnosis of gastric cancer relies on endoscopy and biopsy. Endoscopic ultrasonography and CT of the chest and abdomen are currently the

Surgical treatment

Adequate surgical resection is the only curative therapeutic option for gastric cancer.61, 62 Endoscopic resection might be suitable as an alternative to surgery for small well differentiated early-stage tumours (T1a),55, 63 Advances in technology and minimally invasive strategies have created new opportunities for surgery in gastric cancer. Minimally invasive procedures are associated with reduced surgical trauma and immunosuppression compared with conventional open surgery and, therefore,

Management of locally advanced disease

Adjuvant and neoadjuvant therapies are generally accepted to improve disease-free survival and overall survival in patients who have undergone adequate complete surgical resection (R0) of locally advanced gastric cancer by eradicating microscopic disease locoregionally and at a distance from the primary tumour. 5-year overall survival is increased by 10–15% with the addition of these treatments, but there is no global consensus about the optimum strategy. Perioperative chemotherapy additional

Management of metastatic disease

The outlook for patients with metastatic gastric cancer is very poor, with median survival ranging from 4 months when treated only with best supportive care to around 12 months when treated with combination cytotoxic chemotherapy.82, 83, 84 Studies have also shown improved quality of life. Patients with good performance status scores and with organ function should be offered the option to receive systemic chemotherapy for palliation and to improve survival.

Several cytotoxic agents are active

Conclusions

Progress has been made in understanding the pathogenesis and the molecular biology of gastric cancer and in optimising the available treatment options and modalities. However, in the future, the focus should be on further unravelling the taxonomy of gastric cancer, fine-tuning treatment strategies, and developing new drugs for patients with advanced gastric cancer.

Search strategy and selection criteria

We searched PubMed for articles published in English up to April 30, 2015. We used the search terms “gastric cancer”, “etiology”, “pathology”, “molecular pathogenesis”, “genetics”, “pathophysiology”, “diagnosis”, “chemotherapy”, “radiation”, “surgery”, and “targeted agent”. No other parameters were applied.

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