Oncology & Gastroenterology
Stomach cancer
Stomach cancer - or gastric cancer - is a malignant tumor arising from the gastric mucosa, the most common histological form of which (90-95 %) is gastric adenocarcinoma. It is one of the world's deadliest cancers: the fifth most common cancer in terms of incidence, and the third leading cause of cancer-related death worldwide, with around one million new cases and 769,000 deaths annually (GLOBOCAN 2020). Its prognosis remains bleak due to a predominantly late diagnosis - over 60 % of cases are diagnosed at a metastatic stage (stage IV) in Western countries where there is no mass screening program, in contrast to Japan and South Korea, where systematic endoscopic screening detects 50 to 70 % of gastric cancers at an early, curable stage, with a 5-year survival of over 90 %. In Canada and Quebec, incidence is significantly lower than in East Asia (reduced exposure to Helicobacter pylori, Although gastric cancer is still responsible for around 3,500 deaths a year, it is a major cause of death. Helicobacter pylori - classified as a Group 1 carcinogen by IARC since 1994 - is the main modifiable risk factor, responsible for around 89 % of non-cardial gastric cancers via a cascade of preneoplastic lesions: chronic active gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → adenocarcinoma (Correa cascade). Gastric adenocarcinoma can be divided into two major anatomopathological entities with distinct epidemiologies and prognoses: non-cardial cancer (fundus, body, antrum - the most common, associated with H. pylori and decreasing prevalence in the West) and cancer of the cardia and oesogastric junction (JOG), on the rise in parallel with obesity and chronic gastro-oesophageal reflux, and with a better relative prognosis due to earlier detection.
Risk factors
- Helicobacter pylori - main modifiable carcinogen: chronic infection with H. pylori - present in 50 % of the world population and up to 70-80 % in low-income countries - multiplies the risk of non-cardial gastric cancer by 3 to 6 times via the Correa cascade (chronic gastritis → atrophy → intestinal metaplasia → dysplasia); strains expressing the CagA (cytotoxin-associated gene A) protein - present mainly in East Asia - are particularly oncogenic (risk multiplied by a further 2 to 3 times); eradication of'H. pylori reduces the risk of gastric cancer by 33 to 50 % if performed before the appearance of preneoplastic lesions; eradication after intestinal metaplasia no longer causes lesions to regress, but slows their progression
- Diet: salt-rich diet (salted meats, smoked fish, pickles, cold meats - very common in East Asia, Latin America, Eastern Europe) → chronic irritation of gastric mucosa, potentiation of carcinogenesis by H. pylori ; nitrates and nitrites (deli meats, processed meats) → conversion to carcinogenic nitrosamines in the achlorhydric stomach (atrophic gastritis); diet low in fresh fruit and vegetables - lack of protective antioxidants (vitamin C, beta-carotene)
- Smoking: risk multiplied by 1.5 to 2 - nitrosamine carcinogens swallowed in saliva; synergistic with H. pylori ; increases the risk of cardial and non-cardial cancer
- Conditions predisposing to malignant transformation: autoimmune atrophic gastritis (Biermer anemia - intrinsic factor deficiency, achlorhydria, 3-fold increased risk); gastric intestinal metaplasia (especially type III - incomplete); gastric adenomatous polyps (risk of malignant transformation 10-20 %) ; Ménétrier's disease (hypertrophic gastropathy - risk 10-15 %); old gastric resection (partial gastrectomy for ulcer - cancer of the gastric stump - risk increasing from 15-20 years post-surgery)
- Genetic and hereditary factors : hereditary diffuse gastric cancer (CDHG) - germline mutations of the CDH1 gene (E-cadherin) - cumulative risk of diffuse lobular gastric cancer of 70-80 % in women and 80 % in men; total prophylactic gastrectomy recommended from age 20-30 ; first-degree family history of gastric cancer → 2-3-fold increased risk; HNPCC/Lynch syndrome (MSI-H - microsatellite instability) - increased risk of gastric and colorectal cancer; familial adenomatous polyposis (FAP - APC mutations) - increased risk of gastric fundial polyps and adenocarcinomas.
- Obesity and chronic gastro-oesophageal reflux disease: specific risk factors for cardiac and JOG cancer - abdominal obesity and chronic GERD → Barrett's oesophagus → JOG adenocarcinoma risk; reverse trend for non-cardiac cancer (obesity increases cardia but reduces fundus/antrium)
- Epstein-Barr virus (EBV): present in 5-10 % of gastric adenocarcinomas (EBV-positive form) - associated with preferential fundial localization, better response to immunotherapy (PD-L1 often expressed), better relative prognosis
- Blood group A: slightly increased risk (×1.2) - mechanism not elucidated - historical association described before the discovery of'H. pylori
Symptoms
| Stage / Presentation | Symptoms and clinical signs |
|---|---|
| Early-stage cancer (stage I-II) | Often asymptomatic or non-specific symptoms - vague epigastric discomfort, difficult digestion after meals (dyspepsia), mild nausea, moderate loss of appetite; rarely detected in the absence of an endoscopic screening program; symptoms mimic gastric ulcer or gastritis - hence the importance of performing systematic biopsies at any endoscopy in a patient over 40-45 years of age with persistent dyspepsia |
| Locally advanced cancer (stage III) | Persistent and progressive epigastric pain (different from ulcer pain - less sensitive to antacids); significant weight loss (> 5 % in 3-6 months); marked anorexia; frequent nausea and vomiting (partial gastric obstruction if tumor of antrum or pyloric region) ; dysphagia (if cardiac or JOG localization - difficulty swallowing solids, then liquids); melena (tarry black stools - slow digestive bleeding) or hematemesis (vomiting of blood - more acute bleeding); iron-deficiency anemia due to chronic occult bleeding (fatigue, pallor, tachycardia). |
| Metastatic cancer (stage IV) | Distant signs of extension: Troisier lymph node (hard, painless left supra-clavicular adenopathy - Virchow lymph node metastasis); Sister Mary Joseph lymph node (umbilical nodule - peritoneal carcinosis); carcinomatous ascites (abdominal distension, sloping dullness); hepatomegaly (liver metastases - lumpy liver); Blumer's sign (rectal mass palpable on rectal examination - tumour implant in the cul-de-sac of Douglas); Krukenberg tumour (bilateral ovarian metastases in women - discovered on pelvic ultrasound); severe impairment of general condition, cachexia, paraneoplastic syndrome (acanthosis nigricans, thrombosis - Trousseau syndrome). |
ℹ️
Any persistent (> 4 weeks) upper GI symptom in a patient over 45 - dyspepsia, loss of appetite, unexplained weight loss, nausea - warrants gastroscopy with biopsies, even in the absence of any obvious warning sign. In the West, the absence of a mass screening program means that the majority of gastric cancers are diagnosed late - clinical vigilance in the face of persistent digestive symptoms is the only lever available to improve early diagnosis.
Diagnosis and extension
- Gastroscopy (oesogastroduodenoscopy - OGD) with multiple biopsies: reference examination - direct visualization of the lesion, multiple biopsies (at least 6-8 biopsies per suspected lesion to increase sensitivity); Borrmann macroscopic classification (I: polypoid; II: ulcerating-bourging; III: ulcerating-infiltrating; IV: diffuse infiltrating - plastic linitis); chromoendoscopy and NBI (narrow band imaging) improve detection of early flat lesions
- Gastric echo-endoscopy (GEE): assessment of depth of tumor invasion (T staging) and perigastric adenopathy (local N staging) - complements CT TNM staging for locally advanced tumors; fundamental for guiding the decision of endoscopic resection of T1a (mucosal) cancers vs. surgery
- Thoraco-abdomino-pelvic CT scan with injection (TAP-CT): systematic extension assessment - search for hepatic, pulmonary and distant lymph node metastases, peritoneal carcinosis (limited sensitivity for small peritoneal implants); complete TNM staging essential before any therapeutic decision.
- FDG-PET (positron emission tomography): detects distant lymph node metastases and secondary lesions not visualized on CT; reduced sensitivity for mucinous adenocarcinomas and plastic linitis (low FDG uptake); useful for assessing response to perioperative chemotherapy
- Staging laparoscopy: recommended before curative surgery for T3-T4 tumors - detects peritoneal carcinosis and superficial hepatic implants missed by CT (occult carcinosis in 20-25 % of T3-T4 tumors) - avoids unnecessary laparotomy if carcinosis is confirmed
- Molecular biology and biomarkers : HER2 status (overexpression or amplification of ERBB2 gene) - tested by IHC and FISH on biopsies - positive in 15-20 % gastric adenocarcinomas (especially cardia/JOG) - steers towards trastuzumab (Herceptin) in 1st-line metastasis ; PD-L1 expression (CPS score - Combined Positive Score) - predictive of response to immunotherapy (pembrolizumab); MSI-H status (microsatellite instability - 5-10 % of gastric cancers) - excellent responder to immunotherapy; VEGFR-2 - target of ramucirumab in 2nd line.
- Serum markers: CEA and CA 19-9 - low sensitivity and low specificity for early diagnosis; used for monitoring response to treatment and post-operative surveillance; CA 72-4 - more specific marker for gastric cancer (sensitivity 40-50 %).
Treatment according to stage
- Early stage cancer - endoscopic resection (stage T1a) : endoscopic submucosal dissection (ESD) or endoscopic mucosectomy (EMR) - reference treatment for well-differentiated intramucosal adenocarcinomas (T1a) ≤ 2 cm without ulceration or vascular-lymphatic invasion; cure rate > 95 %; avoids surgical gastrectomy; expanded Gotoda criteria (more extensive T1a adenocarcinomas) - performed mainly in Asian expert centers and in specialized European centers
- Curative surgery - gastrectomy (resectable stages I-III) : subtotal gastrectomy (antrectomy + D2 lymph node dissection) for tumors of the antrum and distal body - preserves quality of life (partial gastric reservoir); total gastrectomy + D2 lymph node dissection for tumors of the proximal body, fundus and plastic linodes; D2 lymph node dissection (dissection of perigastric and celiac trunk lymph nodes) - standard recommended in all specialized centers (reduced recurrence mortality vs. D1); reconstruction with Roux loop or jejunal interposition depending on surgeon and level of resection
- Perioperative chemotherapy (resectable stages II-III): FLOT protocol (fluorouracil, leucovorin, oxaliplatin, docetaxel) - 4 preoperative cycles + 4 postoperative cycles - standard in Europe since the FLOT4 trial (2019) - significant improvement in overall survival vs. ECF/ECX (medians: 50 vs. 35 months); FOLFOX or CAPOX protocol (capecitabine + oxaliplatin) - alternative depending on tolerability; in East Asia: S-1 (oral fluoropyrimidine) or capecitabine as adjuvant alone (ACTS-GC and CLASSIC trials); surgery alone is no longer the standard for tumors > T1b
- Adjuvant radiochemotherapy: combine radiotherapy (45 Gy in 25 fractions) + 5-FU after gastrectomy if lymph node curage is insufficient (D0-D1) - INT-0116 trial (MacDonald 2001); virtually abandoned in Europe and Canada since the advent of perioperative FLOT and D2 curage; still used in the United States.
- Metastatic cancer - 1st line: HER2-positive: trastuzumab (Herceptin) + doublet chemotherapy (CAPOX or FOLFOX) - ToGA trial (2010) - median survival improved from 13.8 to 16 months; trastuzumab deruxtec (T-DXd - Enhertu) approved in 2nd line HER2+ (DESTINY-Gastric02 trial); HER2-negative / PD-L1 CPS ≥ 5: pembrolizumab (Keytruda) + chemotherapy - KEYNOTE-590 and KEYNOTE-811 trial (2022) - significant improvement in overall survival; MSI-H: pembrolizumab monotherapy - response rate 57 %, 5-year survival 27 % (KEYNOTE-158 trial); nivolumab (Opdivo) + chemotherapy - CheckMate-649 trial (2021) - approved for PD-L1 CPS ≥ 5
- Metastatic cancer - 2nd line and beyond: ramucirumab (anti-VEGFR-2 antibody) ± paclitaxel - RAINBOW trial (2014); irinotecan or docetaxel monotherapy depending on tolerability; trastuzumab deruxtec if HER2+; zolbetuximab (anti-CLDN18.2) + CAPOX - SPOTLIGHT trial (2023) - first FDA-approved targeted therapy for CLDN18.2+ in 1st-line metastatic disease (Claudin 18.2 expressed in 40-50 % of gastric cancers)
- Palliative care and symptomatic management: endoscopic or surgical bypass (gastroenterostomy - gastric occlusion); gastrostomy tube or jejunostomy (severe malnutrition); management of cachexia (see cancer cachexia fact sheet); treatment of anemia (transfusions, EPO if chemotherapy); integrated palliative care from diagnosis of metastatic disease.
Prognosis - 5-year survival
| TNM stage | 5-year survival (Western) | Features |
|---|---|---|
| IA (T1N0) | > 90 % | Nodeless intramucosal or submucosal cancer - curative endoscopic or surgical resection; excellent prognosis |
| IB-IIA | 60-80 % | Muscle invasion ± 1-2 lymph nodes; surgery + perioperative chemotherapy |
| IIB-IIIA | 30-50 % | Serous invasion or multiple nodes; curative surgery + FLOT; frequent recurrence within 2 years |
| IIIB-IIIC | 15-25 % | Invasion of adjacent organs or numerous lymph nodes; curative surgery still possible in some cases with pre-operative FLOT |
| IV (M1) | 5-8 % | Metastatic; median survival 12-16 months with immunochemotherapy (pembrolizumab/nivolumab + doublet); MSI-H: better prognosis with immunotherapy (27 % at 5 years) |
Warning signs - urgent medical consultation
Seek medical advice without delay if you experience unexplained weight loss (> 5 % in 1-2 months), dysphagia (difficulty swallowing), persistent vomiting, black or tarry stools (melena), vomiting blood (hematemesis), or intense fatigue associated with pallor - these symptoms may indicate gastric cancer or other serious digestive tract disease requiring urgent gastroscopy. Early diagnosis remains the main determinant of prognosis - treatment at the localized stage multiplies 5-year survival by more than 10 compared with the metastatic stage. Clinique Omicron's doctors can prescribe the initial work-up and refer patients to gastroscopy and the oncology team.
Consult at Clinique Omicron
Clinique Omicron's physicians assess persistent digestive symptoms, prescribe the initial work-up (gastroscopy, blood work-up including CBC and tumor markers), ensure the screening and eradication of'Helicobacter pylori, They also coordinate referrals to partner gastroenterologists and oncologists in the event of a suspected or confirmed lesion. Consultations are available at our points of service in Quebec, as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for informational purposes only and does not replace the advice of a qualified healthcare professional. Any persistent digestive symptoms warrant medical evaluation to exclude serious gastric pathology.
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