A new pathway for the diagnosis, detection and management of patients at risk of gastric adenocarcinoma
Cinzia Papadia, MD, FRCP, Consultant Gastroenterologist at Whipps Cross University Hospital
Gastric adenocarcinoma is the 16th most common cancer in the UK, imposing a considerable burden on healthcare resources. Every year, 6,600 new cases of gastric cancer are diagnosed in the UK, with a five-year survival rate of just 20.7 %, largely owing to late-stage diagnoses.1
A race against the clock
Helicobacter pylori infection is a common cause of gastric adenocarcinoma, triggering a series of premalignant conditions that can eventually culminate in cancer. This process of gastric carcinogenesis follows the histopathological model known as the Correa cascade, which begins with active chronic inflammation, progresses through atrophic chronic gastritis (AG), intestinal metaplasia (GIM) and dysplasia, and concludes with gastric cancer.2 This progressive pathogenesis therefore gives clinicians an opportunity to intervene and implement therapies before it is too late.
Given the role of H. pylori in gastric cancer development, eradication therapies are generally recommended to help reduce the risk of gastric adenocarcinoma in patients with AG. However, it has been hypothesised that when a patient develops GIM or dysplasia, the precancerous cascade reaches a point of no return, at which stage irreversible damage has set in and H. pylori eradication therapies no longer reduce the risk of gastric adenocarcinoma development.3 Therefore, the window of opportunity for effective treatment may be smaller than first thought, reinforcing the need for early diagnosis and intervention.
Screening and surveillance at significant stages along this cascade could help to monitor the development of disease, providing an indication of prognosis to identify those most at risk. Guidelines published by the British Society of Gastroenterology (BSG) in 2019 recommend that endoscopic screening should be considered in patients over the age of 50 with multiple risk factors for gastric adenocarcinoma, including smokers, and those with pernicious anaemia or a first-degree relative with gastric cancer.4 However, this approach is not generally recommended for the general UK population, as the prevalence of gastric cancer is considered to be too low to make screening programmes worthwhile, particularly considering the hefty price tag and long waiting lists associated with endoscopy. However, endoscopic surveillance – with enhanced imaging endoscopy and multiple biopsies as outlined by the Updated Sidney System (USS) – should be offered to patients already diagnosed with extensive GA or GIM every three years.4 In addition, patients with visible intestinal dysplasia or early gastric cancer should undergo endoscopic submucosal resection (EMR) or dissection. 4 It is therefore important to find an efficient, non-invasive and cost-effective method of identifying patients who at higher risk of developing gastric adenocarcinoma and require enhanced imaging endoscopy to enter them into the surveillance program as early as possible.
A new pathway for the detection of gastric adenocarcinoma
The GastroPanel® test is a non-invasive blood test that measures three stomach-specific biomarkers – pepsinogen I, pepsinogen II and gastrin-17, as well as anti-H. pylori IgG antibodies – to examine patients with stomach complaints, and provide an overview of the structure and function of their gastric mucosa. In particular, the detection of serum anti-H. pylori IgG antibody and pepsinogen I to II ratio can identify a patient with extensive chronic AG, as pepsinogen I/II inversely correlates to AG and gastric cancer.5 Crucially, this diagnostic test has been shown to display comparable accuracy to the gold standard gastroscopy and USS biopsy protocol for the classification and grading of gastritis, when diagnosing moderate to severe AG, demonstrating a strong ability to predict corpus AG.6 A similar clinical validation study is currently being conducted at Homerton University Hospital, London, and finding comparative results.
This method is an ideal, cost-effective solution to investigate large numbers of patients presenting with symptoms of dyspepsia – such as epigastric pain, a burning sensation, postprandial fullness and early satiety – but without obvious risk factors or red flag symptoms. A positive result can identify mucosal damage indicative of a condition on the pathway to gastric adenocarcinoma; at which point, high-risk patients can be sent to endoscopy and enrolled on surveillance programs based on BSG guidelines. Conversely, those with negative results can be ruled out unless symptoms are not resolved. The quick and easy test can be requested during clinical appointments, and return actionable results in a timely manner, helping to rapidly identify high-risk patients for urgent referral, and reduce the burden on endoscopy resources.
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- Stomach cancer survival statistics. (2022). Retrieved 14 July 2022, from https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero
- de Vries, A., et al. (2008). Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology, 134(4), 945-952.
- Chen, H. N., Wang, Z., Li, X., & Zhou, Z. G. (2016). Helicobacter pylori eradication cannot reduce the risk of gastric cancer in patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis. Gastric Cancer, 19(1), 166-175.
- Banks, M., et al. (2019). British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut, 68(9), 1545-1575.
- Lansdorp-Vogelaar, I., & Kuipers, E. J. (2016). Screening for gastric cancer in Western countries. Gut, 65(4), 543-544.
- Koivurova O-P, et al. (2021). Serological biomarker panel in diagnosis of atrophic gastritis and Heliobacter pylori infection in gastroscopy referral patients. Clinical validation of the new generation GastroPanel® Anticancer Res, 41, 5527-37.