Gastric cancer is the cancer originating in the esophagus, esophagogastric junction and stomach.
Most of gastric cancers are adenocarcinomas, subdivided according to histological appearances into diffuse (undifferentiated) and intestinal (well differentiated) types.
It is the 4th most common cancer and the 2nd most common cause of cancer-related deaths worldwide.
Most common sites of gastric cancer are the proximal lesser curvature, cardia and esophagogastric junction.

Supportive Therapy

  • Should be considered in patients with stage IV disease that can improve survival compared with best supportive care alone
    • Co-morbidities, organ function and performance status must always be taken into consideration
  • Decision to offer palliative or best supportive care alone or in combination with systemic therapy is based on the patient's performance status


  • May be an option for medically fit patients with locally unresectable tumors and have no previous therapy
  • Preferred regimens include:
    • Cisplatin and Fluorouracil
    • Cisplatin and Capecitabine
    • Oxaliplatin and Fluorouracil
    • Oxaliplatin and Capecitabine
  • Other recommended regimens include: Fluoropyrimidine (Fluorouracil or Capecitabine) and Paclitaxel
Systemic Therapy
  • Provides palliation of symptoms, enhances quality of life and improves survival of patients with locally advanced or metastatic gastric cancer

First-line Therapy

  • Two-drug cytotoxic combination regimens are preferred due to lower toxicity
  • Three-drug cytotoxic combination regimens are reserved for medically fit patients with good performance status
  • Combination regimens based upon a platinum-fluoropyrimidine doublet are preferred
    • Fluoropyrimidine (5-FU or Capecitabine) and Cisplatin or Oxaliplatin
  • Other recommended regimens include:
    • Docetaxel
    • Docetaxel and Cisplatin
    • Docetaxel, Cisplatin and Fluorouracil (DCF)
      • Has been recommended as alternative treatment option for the treatment of patients with advanced gastric cancer, including EGJ cancers, in patients who have not received prior chemotherapy
      • However, it was associated with increased myelosuppression and infectious complications
    • DCF modifications
      • Docetaxel, Carboplatin and Fluorouracil
      • Docetaxel, Oxaliplatin and Fluorouracil
    • Epirubicin, Cisplatin and Fluorouracil (ECF)
    • ECF modifications
      • Epirubicin, Cisplatin and Capecitabine
      • Epirubicin, Oxaliplatin and Capecitabine
      • Epirubicin, Oxaliplatin and Fluorouracil
    • Fluoropyrimidine (Fluorouracil or Capecitabine)
    • Fluorouracil and Irinotecan
    • Paclitaxel
    • Paclitaxel and Cisplatin or Carboplatin
  • Oxaliplatin is preferred due to its lower toxicity over Cisplatin

Second-line or Subsequent Therapy

  • Choice of agents depends on previous therapy and performance status
  • Preferred regimens include:
    • Docetaxel
    • Fluorouracil and Irinotecan
    • Irinotecan
    • Paclitaxel
    • Pembrolizumab
      • Indicated as second-line or subsequent therapy for MSI-H or dMMR tumors and third-line or subsequent therapy for gastric adenocarcinoma with PD-L1 expression levels by CPS ≥1
    • Ramucirumab and Paclitaxel
    • Trifluridine and Tipiracil
      • Indicated as third-line or subsequent therapy for select patients with low-volume gastric cancer without or minimal symptoms and with the ability to swallow pills
  • Other recommended regimens include:
    • Docetaxel and Irinotecan
    • Entrectenib or Larotrectenib for NTRK gene fusion-positive tumors
    • Irinotecan and Cisplatin
    • Ramucirumab
  • Fluorouracil and Irinotecan + Ramucirumab combination therapy may be useful in certain circumstances
  • In patients of adequate performance status, second-line chemotherapy is associated with proven improvements in overall survival and quality of life compared with best supportive care

Targeted Therapies

  • Human epidermal growth factor receptor-2 (HER-2) testing is recommended for all patients with inoperable, locally advanced, recurrent and metastatic disease at the time of diagnosis
  • In HER-2-positive gastric cancer, addition of Trastuzumab to a Cisplatin-Fluoropyrimidine doublet showed clinically and statistically significant improvements in response rate, progression-free survival and overall survival
    • Trastuzumab in combination with Cisplatin and fluoropyrimidine (first-line) or with other chemotherapy agents (eg Capecitabine or 5-fluorouracil and Oxaliplatin) is the standard care regimen
    • Trastuzumab was limited only in patients with an immunohistochemistry score of 3+ or 2+ and FISH positive
    • Trastuzumab is not recommended to be continued in second-line therapy
  • Targeting vascular endothelial growth factor receptors (VEGFR) with the anti-vascular endothelial growth factor receptors 2 (VEGFR-2) monoclonal antibody Ramucirumab showed promising results in patients with advanced gastric or EGJ adenocarcinoma positive for disease progression despite treatment with platinum-/fluoropyrimidine-based doublet/triplet chemotherapy
    • Ramucirumab may be given alone or in combination with Paclitaxel
  • Pembrolizumab is a PD-1 antibody
    • Preferred as second-line or subsequent therapy for MSI-H or dMMR tumors and third-line or subsequent therapy for PD-L1-positive gastric adenocarcinoma with CPS ≥1
  • Entrectenib or Larotrectenib is recommended as second-line or subsequent therapy for NTRK gene fusion-positive tumors

Palliative/Best Supportive Care

  • Recommended for all patients with unresectable locally advanced, recurrent or metastatic gastric cancer
  • Goal is to prevent, reduce and relieve suffering and improve the quality of life for patients and their families

Interventional Radiotherapy

  • Angiographic embolization may be considered in patients with acute bleeding not relieved by endoscopy


  • Hypofractionated radiotherapy is an effective and well-tolerated treatment modality which may palliate bleeding, obstructive symptoms or pain in patients with symptomatic locally advanced or recurrent disease
  • External beam radiotherapy may be considered for patients with malignant obstruction causing pain, and acute or chronic gastrointestinal bleeding


  • Surgeries that will aid the patients with unresectable gastric cancer control the cancer or prevent or relieve symptoms or complications 
  • Although resection of the primary tumor is not generally recommended in the palliative setting, a small number of advanced disease patients may be deemed to be operable following a good response in systemic therapy
  • Gastric resections should be reserved for palliation of symptoms such as obstruction or uncontrollable bleeding in patients with incurable disease
    • Gastrojejunostomy or gastrectomy may be done to alleviate or bypass obstruction
      • Gastrojejunostomy is preferred for gastric outlet obstruction over endoluminal stenting for patients fit for surgery and with a more prolonged prognosis 
    • Lymph node dissection is not required
  • Subtotal gastrectomy can help in problems of bleeding, pain or blockage in the stomach
  • Limited gastric resection, even with positive margins, is acceptable for unresectable tumors for symptomatic palliation of bleeding
    • Presence of peritoneal involvement, distant metastases, or locally advanced disease (eg invasion or encasement of major blood vessels) are contraindications for resection
  • Routine or prophylactic splenectomy should be avoided if possible
  • Gastric bypass (gastrojejunostomy) can treat or prevent large tumors that block food from leaving the stomach
    • For selected patients who will be receiving postoperative chemoradiation, placement of a venting gastrostomy or jejunostomy feeding tube may be considered
  • Endoscopic tumor ablation helps to stop bleeding or help relieve blockage without surgery
    • For short-term control of bleeding
  • Stent placement helps keep the opening at the beginning and end of the stomach open and allows food to pass through it
    • Endoscopic insertion of self-expanding metal stents (SEMS) has been shown to be effective for the long-term relief of tumor obstruction at the gastric outlet or EGJ
      • Preferred over gastrojejunostomy for patients with luminal obstruction secondary to advanced gastric cancer and with relatively short life expectancy
  • Venting gastrostomy may be performed to reduce symptoms of obstruction when bypass or alleviation is not possible
  • Feeding tube placement is done to help in the liquid nutrition that can be put directly into the tube
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