Seminar

Gastric cancer
Elizabeth C Smyth, Magnus Nilsson, Heike I Grabsch, Nicole CT van Grieken, Florian Lordick

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk Lancet 2020; 396: 635–48
factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Department of Oncology,
Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, Cambridge University
Hospitals National Health
and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early
Service Foundation Trust,
gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include Hill’s Road, Cambridge, UK
D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial (E C Smyth MD); Division of
branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Surgery, Department of Clinical
Science, Intervention and
Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine
Technology, Karolinska
doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include Institute, Stockholm, Sweden
trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or (M Nilsson PhD); Department of
pembrolizumab (anti-PD-1 third line). Upper Abdominal Diseases,
Karolinska University Hospital,
Stockholm, Sweden
Epidemiology and risk factors damage at the time of eradication. According to current (M Nilsson); Department of
Gastric cancer is a globally important disease. With over recommendations, eradi­cation of H pylori should be done Pathology, GROW School for
1 million estimated new cases annually, gastric cancer is in the following risk populations: pan-gastritis and corpus- Oncology and Developmental
Biology, Maastricht University
the fifth most diagnosed malignancy worldwide. Due to predominant gastritis, first-degree relatives of patients Medical Center+, Maastricht,
its frequently advanced stage at diagnosis, mortality from with gastric cancer, and previous gastric neoplasia.11–14 Risk Netherlands (H I Grabsch PhD);
gastric cancer is high, making it the third most com­ factors beyond H pylori for non-cardia gastric cancer are Pathology and Data Analytics,
mon cause of cancer-related deaths, with 784 000 deaths older age, low socio-economic status, cigarette smoking, Leeds Institute of Medical
Research at St James’s,
globally in 2018.1 Hotspots of inci­dence and mortality for alcohol consumption, familial predis­ position, previous University of Leeds, Leeds, UK
gastric cancer exist in East Asia, Eastern Europe, and gastric surgery, pernicious anaemia, and living in a (H I Grabsch); Department of
South America (figure 1). The incidence of gastric cancer population at high risk.15–17 Salted food intake might Pathology, Amsterdam
is two times higher in males than in females.1 A steady increase the risk of H pylori infection and could also act University Medical Centre,
Cancer Center Amsterdam,
decline in the incidence and mortality rates of this cancer synergistically to promote the develop­ ment of gastric VU University, Amsterdam,
have been observed over the past century. However, cancer. Therefore, dietary modification involving less salt Netherlands
despite declining incidence rates in most countries, and salted food intake is one possible strategy to prevent (N C T van Grieken PhD);
clinicians can expect to see more gastric cancer cases in gastric cancer. Gastric cancer risk might be decreased and University Cancer Center
Leipzig, Leipzig University
the future due to ageing populations. Improved living with a high intake of fruit and vegetables.18 In contrast to Medical Center, Leipzig,
conditions associated with economic development have distal gastric cancer, a positive association between gastro- Germany (F Lordick MD)
contributed to the reduction in the prevalence of oesophageal reflux disease and proximal (cardia type) Correspondence to:
Helicobacter pylori, the major cause of gastric cancer.3 In gastric cancer has been shown.19,20 Dr Elizabeth C Smyth,
high incidence areas such as Japan and Korea, screening Department of Oncology,
Cambridge University Hospitals
programmes have also led to substantial reductions Genetics of gastric cancer National Health Service
in gastric cancer associated mortality.4–6 An observed Approximately 10% of all gastric cancer cases show familial Foundation Trust, Hill’s Road,
increase in the incidence in younger people from aggregation and 1–3% of patients with gastric cancer have Cambridge CB2 0QQ, UK
high-income countries suggests a change in disease risk germline mutations.21 Hereditary forms of gastric cancer elizabeth.smyth2@nhs.net

and epidemiology of gastric cancer. Attention to ongoing
transitions in gastric cancer epidemiology is therefore
relevant to future cancer control and clinical practice.7
H pylori infection is the most well described risk factor
for non-cardia gastric cancer. Chronic infection of the
gastric mucosa leads to stepwise progression from
atrophic gastritis and intestinal metaplasia.8 The majority
of the population infected with H pylori remain asymp­
tomatic. Gastric cancer due to H pylori infection is
associated with bacterial virulence, genetic polymorphism
of hosts, and environmental factors. Most H pylori strains
possess a cytotoxin-associated gene A (CagA) pathogen­
icity island, encoding a 120–140 kDa CagA protein,
an oncoprotein that affects the expression of cellular
signalling proteins.9,10 Treatment of H pylori can reduce the
risk of transformation to gastric cancer, but the magnitude
of risk reduction depends on the degree of pre-existing
can be subdivided into three groups:21–23 hereditary diffuse
type gastric cancer (HDGC; autosomal dominant; <1% all
gastric cancer); familial intestinal gastric cancer (autosomal
dominant); and gastric adeno­ carcinoma with proximal
polyposis of the stomach (autosomal dominant).
Search strategy and selection criteria
We searched PubMed and abstracts from international
conferences (American Society of Clinical Oncology, European
Society of Medical Oncology [ESMO], and ESMO World
Congress on Gastrointestinal Cancer) between Nov 26, 2019,
and May 29, 2020, with the search terms “gastric cancer”,
“gastroesophageal cancer”, “surgery”, “genetics”,
“chemotherapy”, “targeted therapy”, and “immunotherapy”.
We only searched for articles and abstracts published in English.

www.thelancet.com Vol 396 August 29, 2020 635

The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5
The Lancet, 396 (2020) 635-648. doi:10.1016/S0140-6736(20)31288-5