Gastric Cancer

After diagnostic endoscopy establishes gastric cancer, obtain CT of the thorax, abdomen, and pelvis for initial staging and risk assessment. In apparently resectable disease, use endoscopic ultrasonography when locoregional T and N assessment will affect the choice between local resection, surgery, and perioperative therapy. ScienceDirectScienceDirectGastric cancer: ESMO–ESSO–ESTRO Clinical Practice ...

Use staging laparoscopy to look for occult peritoneal metastases when imaging does not show distant disease but peritoneal risk is substantial, particularly with cT3/cT4 tumors or poorly cohesive histology. Occult peritoneal metastasis or positive cytology redirects management away from curative gastrectomy toward treatment for unresectable/metastatic disease. Nature+1NatureNon-invasive liquid biopsy based on transcriptomic profiling for early diagnosis of occult peritoneal metastases in locally advanced gastric cancer | npj Precision OncologyScienceDirectGastric cancer: ESMO–ESSO–ESTRO Clinical Practice ...

Make resectability the first therapeutic branch: cT1N0 disease may be treated by endoscopic or surgical resection alone, whereas cT2 and/or cN-positive disease should enter a perioperative-treatment and surgical-planning pathway. ScienceDirectScienceDirectGastric cancer: ESMO–ESSO–ESTRO Clinical Practice ...

For cT1N0 gastric cancer, endoscopic or surgical resection alone is appropriate when local therapy can achieve oncologic control. Do not automatically expose this group to perioperative systemic therapy intended for clinically advanced disease. ScienceDirectScienceDirectGastric cancer: ESMO–ESSO–ESTRO Clinical Practice ...

For localized cT2 and/or cN-positive gastric cancer, perioperative FLOT is the recommended standard approach in the cited guideline pathway. FLOT includes fluorouracil, leucovorin, oxaliplatin, and docetaxel; the cited NCCN regimen summary lists leucovorin 200 mg/m² IV on day 1 within FLOT. ScienceDirect+1ScienceDirectGastric cancer: ESMO–ESSO–ESTRO Clinical Practice ...PubMedTable 8, Summary of Leucovorin Doses in Different Fluorouracil-Based Regimens - Leucovorin Dosing for Gastrointestinal Cancer - NCBI Bookshelf

Plan radical gastrectomy with D2 lymphadenectomy after perioperative treatment in patients who remain operable and free of metastatic progression. D2 nodal dissection is the operative standard described across surgical gastric cancer trial and guideline materials. cell+2cellMulticenter, Prospective Phase II Clinical TrialNatureNeoadjuvant FLOT versus SOX phase II randomized ...ScienceDirectPan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer

For unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, establish HER2 status, MMR/MSI status, PD-L1 expression, and CLDN18.2 expression before first-line systemic therapy. Regimen selection is driven by these results together with performance status and prior therapy. NatureNatureDigestive cancers: mechanisms, therapeutics and management | Signal Transduction and Targeted Therapy

Assess PD-L1 by immunohistochemistry using the combined positive score or tumor proportion score, recognizing that PD-L1 expression is a predictive biomarker for immune checkpoint inhibitor treatment in gastroesophageal cancers. MSI-H/dMMR is also predictive for checkpoint-inhibitor benefit and can identify patients with activity from pembrolizumab independent of PD-L1 CPS in previously treated disease. Nature+1NatureDigestive cancers: mechanisms, therapeutics and management | Signal Transduction and Targeted TherapyPubMedNovel Biomarkers of Gastric Cancer: Current Research and Future Perspectives - PMC

Interpret HER2 as a therapeutic branch rather than a generic molecular descriptor. HER2 overexpression/amplification predicts HER2-directed treatment; the cited review defines HER2-positive disease as IHC 3+ or IHC 2+ with FISH positivity in the trastuzumab deruxtecan-treated advanced gastric/GEJ population. PubMedPubMedNovel Biomarkers of Gastric Cancer: Current Research and Future Perspectives - PMC

Use CLDN18.2 testing in HER2-negative advanced disease because CLDN18.2 positivity identifies patients eligible for first-line zolbetuximab plus chemotherapy. CLDN18.2 expression has little overlap with HER2 and high PD-L1 overexpression in reported trial commentary, which makes its early measurement clinically useful rather than a later-line reflex test. PubMed+2PubMedClinical Review - Zolbetuximab for Injection (Vyloy) - NCBI BookshelfASCOZolbetuximab Succeeds Yet Again in CLDN18.2-Positive Advanced Gastric/Gastroesophageal Junction Cancer in First-Line Phase 3 GLOW TrialESMONew Claudin 18.2 approach shows promise in gastric cancer

For advanced HER2-positive gastric cancer, use chemotherapy plus trastuzumab and pembrolizumab as the cited first-line standard. This branch requires confirmation of HER2 positivity before treatment and should not be extrapolated to HER2-negative tumors. Wolters KluwerWolters KluwerOvercoming resistance in HER2-positive gastric cancer: a... : Annals of Medicine and Surgery

For HER2-negative advanced gastric/GEJ adenocarcinoma, fluoropyrimidine- and oxaliplatin-based chemotherapy remains the backbone of contemporary combination therapy. FOLFOX is identified as a typical first-line chemotherapy platform, with nivolumab or pembrolizumab used in combination in current practice discussions; the cited regimen summary lists leucovorin 400 mg/m² IV on day 1 for modified FOLFOX6. PubMed+1PubMedTable 8, Summary of Leucovorin Doses in Different Fluorouracil-Based Regimens - Leucovorin Dosing for Gastrointestinal Cancer - NCBI BookshelfPubMedClinical Review - Zolbetuximab for Injection (Vyloy) - NCBI Bookshelf

For HER2-negative, CLDN18.2-positive disease, zolbetuximab plus chemotherapy is an effective first-line alternative, particularly when immune checkpoint inhibitors are contraindicated or PD-L1 expression is low. When CLDN18.2 positivity coexists with PD-L1 CPS above 5%, the optimal choice among zolbetuximab, nivolumab, or pembrolizumab remains uncertain and should be individualized according to comorbidity and patient priorities. Oxford Academic+1Oxford Academicpatient selection for zolbetuximab in advanced treatment-naïve ...PubMedClinical Review - Zolbetuximab for Injection (Vyloy) - NCBI Bookshelf

For MSI-H/dMMR disease, give immunotherapy substantial weight in first-line strategy selection because this phenotype predicts checkpoint-inhibitor responsiveness. In previously treated MSI-H gastric/GEJ cancer, pembrolizumab activity was reported regardless of PD-L1 CPS; this supports avoiding a PD-L1-only interpretation of an MSI-H result. PubMed+1PubMedNovel Biomarkers of Gastric Cancer: Current Research and Future Perspectives - PMCPubMedThe New Era of Immunotherapy in Gastric Cancer - PubMed

For HER2-positive locally advanced or metastatic gastric/GEJ cancer that has progressed after at least two prior regimens including trastuzumab, trastuzumab deruxtecan improved objective response and overall survival in the cited DESTINY-Gastric01 evidence summary. This is a later-line HER2-directed option rather than a substitute for first-line trastuzumab-based treatment. PubMedPubMedNovel Biomarkers of Gastric Cancer: Current Research and Future Perspectives - PMC

Nivolumab demonstrated overall-survival improvement as later-line treatment in unselected advanced gastric cancer in ATTRACTION-2 and as first-line therapy with chemotherapy in CheckMate-649. Apply checkpoint inhibition according to prior treatment exposure, tumor biomarkers, and regional regulatory indications rather than assuming all PD-1 regimens are interchangeable. PubMedPubMedThe New Era of Immunotherapy in Gastric Cancer - PubMed

At each radiographic or clinical progression, review whether HER2, MMR/MSI, PD-L1, and CLDN18.2 were obtained before first-line therapy; if a core result is missing, obtain it before bypassing an indicated targeted or immune-based branch. Broader genomic sequencing should be reserved for selected cases because its routine benefit in gastric cancer remains less clear. NatureNatureDigestive cancers: mechanisms, therapeutics and management | Signal Transduction and Targeted Therapy