Gastric cancer: recognising alarm features and the AU GP pathway

What gastric cancer is

Stomach (gastric) cancer kills more than 1,200 Australians each year and is diagnosed at a late stage in most patients. The five-year relative survival rate is approximately 30% across all stages — but this masks a steep stage gradient: patients with stage I disease exceed 80% survival, while those with distant metastases remain below 10%. Stage at diagnosis is therefore the strongest determinant of outcome, and the general practitioner is the first line of detection.

The Australian Institute of Health and Welfare estimates around 2,300 new gastric cancer diagnoses annually in Australia, with incidence declining approximately 2% per year — largely attributed to declining Helicobacter pylori prevalence, refrigeration replacing preserved and salt-cured foods, and increasing endoscopy access. Men are diagnosed almost twice as often as women. Australia has no population-based gastric cancer screening programme (unlike South Korea and Japan), so symptomatic recognition and targeted high-risk identification remain the primary GP tools.

A. Core clinical — the AU general-practice framework

Pathology and the Correa cascade

Approximately 95% of gastric cancers are adenocarcinomas, classified by Lauren into two main types:

• Intestinal type — well-differentiated, gland-forming, typically arising in the distal stomach; follows the Correa cascade: H. pylori infection → chronic active gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → adenocarcinoma, evolving over decades; more common in older adults and high-incidence migrant populations
• Diffuse type — poorly cohesive signet-ring cells, often presenting as linitis plastica (leather-bottle stomach on imaging); more common in younger adults; associated with CDH1 germline mutation; does not follow the Correa cascade and lacks reliable endoscopic precursors

Other histologies — gastrointestinal stromal tumour (GIST), MALT lymphoma, neuroendocrine tumour — are less common and managed through distinct pathways.

H. pylori and cancer risk

Helicobacter pylori is classified by the International Agency for Research on Cancer as a definite Group 1 carcinogen for gastric adenocarcinoma. Chronic infection confers approximately a 6-fold relative risk compared with H. pylori-negative individuals; absolute lifetime cancer risk is 1–3% in carriers. H. pylori eradication reduces subsequent gastric cancer incidence by approximately 50% in randomised trials when administered before intestinal metaplasia establishes — but does not eliminate risk once advanced Correa-cascade changes are present.

Risk factors

Risk factor	Approximate relative risk
H. pylori chronic infection	~6×
CDH1 germline mutation	~70% lifetime (men)
First-degree relative with gastric cancer	2–3×
Pernicious anaemia / severe atrophic gastritis	3–6×
Smoking	1.5–2×
High-salt / processed meat diet	1.5–2×
East Asian or South American country of birth	2–4× (country-specific variation)

Presentation

Gastric cancer typically presents late with symptoms indistinguishable from peptic ulcer disease or functional dyspepsia — a major contributor to diagnostic delay. Common presentations include:

• Epigastric discomfort, heartburn, or early satiety
• Nausea, anorexia, and unexplained weight loss
• Dysphagia (particularly with cardia and gastro-oesophageal junction tumours)
• Haematemesis or melaena from overt bleeding
• Iron-deficiency anaemia from occult blood loss — often the presenting laboratory finding in otherwise well patients

Alarm features — the 2-week-pathway trigger

RACGP red-flag guidance and the Cancer Australia optimal care pathway specify that any of the following in a patient presenting with dyspepsia or epigastric symptoms should trigger urgent 2-week-pathway gastroscopy — not an empirical antacid trial:

• Unexplained involuntary weight loss
• Dysphagia
• Iron-deficiency anaemia with no other explanation
• Persistent vomiting (more than one episode per day for more than one week)
• Haematemesis or melaena
• Palpable epigastric mass
• Virchow’s node — left supraclavicular lymphadenopathy (Troisier’s sign)
• Adults aged 55 or over with new persistent dyspepsia, particularly with relevant family history

B. Diagnosis and biomarker-driven staging

Gastroscopy and biopsy

Upper endoscopy with systematic biopsy — minimum six samples from the lesion, plus antrum and body biopsies for H. pylori — is the diagnostic cornerstone. Biopsy reports should specify Lauren classification, tumour grade, depth of invasion (T stage), and HER2 immunohistochemistry. Therapeutic Guidelines (eTG) provides the standard workup sequence for gastric malignancy.

Staging investigations

• CT chest/abdomen/pelvis with IV contrast — primary tumour extent, regional lymph nodes, hepatic and pulmonary metastases
• Endoscopic ultrasound (EUS) — locoregional T and N staging; essential before deciding perioperative chemotherapy versus primary surgical resection
• PET-CT — Authority required; identifies occult distant disease and clarifies equivocal CT findings
• Staging laparoscopy — recommended before perioperative chemotherapy to exclude peritoneal carcinomatosis invisible on CT (found in approximately 30% of locally advanced cases at laparoscopy)

Biomarker testing

All advanced or metastatic gastric adenocarcinoma specimens require four biomarkers that directly determine systemic therapy:

Biomarker	Test	Positive threshold	Therapy implication
HER2	IHC ± FISH	IHC 3+ or IHC 2+/FISH+	Trastuzumab eligible
PD-L1 CPS	IHC	CPS ≥5	Checkpoint inhibitor eligible
MMR/MSI	IHC or PCR	dMMR/MSI-H	Augmented IO benefit; Lynch syndrome screen
CLDN18.2	IHC	≥75% of cells, intensity ≥2+	Zolbetuximab eligible

C. Treatment by stage

Very early (T1a): endoscopic resection

For T1a mucosal gastric cancer ≤2 cm, well-differentiated, without ulceration, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) achieves equivalent oncological outcomes to surgical gastrectomy with substantially less morbidity. These procedures are performed at specialist endoscopy centres with high-volume experience. eviQ publishes the eligibility criteria for ESD versus EMR selection.

Locally advanced (T2+ or node-positive): perioperative chemotherapy plus surgery

The Australian standard is perioperative FLOT chemotherapy — fluorouracil, leucovorin, oxaliplatin, and docetaxel — 4 pre-operative cycles followed by surgery then 4 post-operative cycles, based on the FLOT4 trial (Lancet 2019). FLOT demonstrated three-year overall survival of 57% versus 48% for ECF/ECX regimens. Gastrectomy extent (total vs subtotal) is determined by tumour location.

Advanced/metastatic: biomarker-guided systemic therapy

First-line treatment per ESMO guidelines:

• All comers — platinum and fluoropyrimidine doublet chemotherapy as the backbone
• PD-L1 CPS ≥5 — add nivolumab per CheckMate 649 (Lancet 2021), or pembrolizumab per KEYNOTE-859 (Lancet Oncology 2023)
• HER2-positive (~12–15% of cases) — add trastuzumab per the ToGA trial (Lancet 2010); second-line trastuzumab deruxtecan for HER2-positive progression
• CLDN18.2-positive — zolbetuximab plus chemotherapy per the SPOTLIGHT trial (Lancet 2023), demonstrating improved overall and progression-free survival

All systemic treatment decisions are made at a multidisciplinary oncology team meeting; PBS-approved protocols are available on eviQ.

D. Australian operations

Urgent referral and 2-week pathway

GPs should directly arrange urgent gastroscopy (through a public gastroenterology service or private endoscopist) targeting completion within 14 days of the referral decision when alarm features are identified. Simultaneously document weight trajectory, family history of gastric or lobular breast cancer, H. pylori status, and current medications (NSAIDs, anticoagulants, aspirin).

For established gastric cancer, refer without delay to a Cancer Australia-accredited upper GI multidisciplinary team. The pathway targets first contact with a cancer specialist within 14 days of diagnosis.

H. pylori test-and-treat in general practice

eTG recommends test-and-treat for uninvestigated dyspepsia in adults under 55 without alarm features. The preferred non-invasive tests are the urea breath test or stool antigen test. Standard first-line eradication uses 7-day triple therapy (PPI + amoxicillin + clarithromycin) or quadruple bismuth therapy — increasingly preferred given rising clarithromycin resistance. Confirm eradication with urea breath or stool antigen test at least 4 weeks after completing therapy, with PPI ceased for at least 2 weeks beforehand.

MBS and PBS

• MBS 30473 — upper gastrointestinal endoscopy with biopsy
• MBS 73296/73297 — CDH1 germline genetic testing via specialist clinical genetics referral
• MBS 55054/55056 — staging CT abdomen/pelvis
• PBS — trastuzumab (Authority, HER2+), capecitabine, oxaliplatin, and nivolumab (Authority, PD-L1 CPS ≥5, first-line advanced gastric) are PBS-listed

CDH1 cascade referral

When diffuse gastric cancer or lobular breast cancer is identified in a family, refer to a familial cancer service for CDH1 germline testing. Genetic testing is MBS-rebated under items 73296/73297 with specialist referral. Pre- and post-test genetic counselling is coordinated through the specialist service. Cancer Council Australia provides consumer-level information for affected families.

Post-gastrectomy GP surveillance

Patients after total or partial gastrectomy require structured follow-up:

• Vitamin B12: hydroxocobalamin 1 mg IM every 3 months after total gastrectomy — oral B12 is not reliably absorbed without intrinsic factor
• Iron: serum ferritin and iron studies 3–6 monthly initially; oral ferrous sulfate or IV iron depending on tolerance and absorption capacity
• Calcium and vitamin D: annual bone density assessment from 2–3 years post-operatively; supplement as indicated
• Annual bloods: full blood count, B12, iron studies, vitamin D, calcium, and liver function tests (metastasis screen)
• Dietitian referral: manage dumping syndrome, nutritional deficits, and weight restoration post-operatively

E. Special populations

Hereditary diffuse gastric cancer (CDH1/HDGC)

Germline CDH1 mutations cause hereditary diffuse gastric cancer (HDGC), conferring approximately 70% lifetime gastric cancer risk in men and 56% in women, plus about 42% lobular breast cancer risk in women, per the IGCLC 2020 international guidelines. The gastric lesions are multifocal signet-ring cell foci that are endoscopically invisible — surveillance gastroscopy is unreliable for early detection. Prophylactic total gastrectomy between ages 20 and 30 is the standard recommendation for CDH1 carriers after comprehensive genetic and surgical counselling. Women with CDH1 mutations require annual breast MRI surveillance from age 30 for lobular breast cancer risk reduction.

Cascade testing indications: two or more first-degree relatives with gastric cancer (one under 50), or three or more affected relatives regardless of age. Refer to a familial cancer clinic; the clinical genetics team leads the discussion.

Young adults with diffuse-type gastric cancer

Diffuse-type gastric cancer disproportionately affects younger adults, often without prior H. pylori infection. A person under 40 with unexplained weight loss and progressive epigastric symptoms should not be reassured solely on the basis of age. Linitis plastica on CT — a thickened, non-distensible stomach — is a red flag requiring urgent specialist referral regardless of H. pylori status or symptom duration.

High-incidence immigrant communities

East Asian-born (Japanese, Korean, Chinese) and South American-born communities carry substantially higher age-standardised gastric cancer rates from their countries of origin. There is no population-wide screening programme in Australia. Opportunistic discussion of alarm features, H. pylori testing, and relevant dietary risk factors is appropriate at preventive health consultations for patients from these backgrounds. Refer to RACGP guidelines on refugee and migrant health for broader clinical context.

Older and frail patients

FLOT perioperative chemotherapy carries significant haematological and systemic toxicity — docetaxel in particular. Older and frail patients require formal geriatric assessment before committing to full-dose perioperative regimens. Modified regimens (CAPOX, ECX) or best supportive care with palliative intent may be appropriate. GP input on functional status, comorbidities, social circumstances, and advance care planning is invaluable at the multidisciplinary meeting.

When to escalate

• Dyspepsia with any alarm feature → arrange urgent 2-week-pathway gastroscopy today; do not start a proton pump inhibitor and review in 4–6 weeks
• Gastroscopy showing gastric mass, suspicious ulcer, or irregular mucosa → urgent upper GI oncology referral; do not wait for formal pathology before contacting the referral centre
• Established gastric cancer → immediate multidisciplinary team referral; request all biomarker results and ensure staging CT is completed
• Family history suggestive of HDGC (diffuse gastric cancer, lobular breast cancer, CDH1 family history) → refer to familial cancer service for genetic testing
• Post-gastrectomy B12 or iron deficiency → replace and monitor; if deficiency persists despite replacement, discuss with treating team
• New symptoms in the follow-up period → low threshold to re-image and re-endoscope; do not attribute new epigastric symptoms to functional causes without investigation

What this article is and is not

This article provides a general-practice framework for recognising, referring, and supporting patients with gastric cancer in Australia, drawing on AIHW 2024, Cancer Australia optimal care pathways, ESMO guidelines, Therapeutic Guidelines (eTG), and trial data from FLOT4, CheckMate 649, and ToGA. It does not replace specialist oncology, surgery, gastroenterology, or genetic medicine advice. Systemic treatment regimens are biomarker-driven, evolve rapidly, and are decided at multidisciplinary team meetings — always defer to the treating oncologist and eviQ protocols. Nothing in this article constitutes clinical advice for any individual patient.

For Australian consumer-friendly information: Cancer Council Australia — Stomach cancer.

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Sources cited

1. AIHW — Cancer Data in Australia 2024 (stomach cancer)
2. Cancer Council Australia — Stomach cancer
3. Cancer Australia — Optimal care pathway for oesophagogastric cancer
4. eviQ — Gastric/GEJ cancer protocols (Cancer Institute NSW)
5. RACGP — Suspected cancer red flags and 2-week pathway
6. eTG complete — Gastric cancer
7. ESMO Clinical Practice Guidelines — Gastric cancer 2022
8. FLOT4 — Al-Batran SE et al. Perioperative FLOT vs ECF. Lancet 2019;393:1948
9. CheckMate 649 — Janjigian YY et al. Nivolumab plus chemo, gastric/GEJ. Lancet 2021;398:27
10. KEYNOTE-859 — Rha SY et al. Pembrolizumab plus chemo, gastric. Lancet Oncol 2023;24:1181
11. ToGA — Bang YJ et al. Trastuzumab plus chemo, HER2+ gastric. Lancet 2010;376:687
12. SPOTLIGHT — Shitara K et al. Zolbetuximab plus mFOLFOX6. Lancet 2023;401:1655
13. IARC Monograph 100B — Helicobacter pylori (Group 1 carcinogen)
14. IGCLC 2020 — Blair VR et al. Hereditary diffuse gastric cancer guidelines. Lancet Oncol 2020;21:e386
15. Lee YC et al. H. pylori eradication and gastric cancer prevention. Gastroenterology 2016;150:1113