Gastric Adenocarcinoma

Background

• Gastric cancer incidence is highest in Eastern Asia, Eastern Europe, and South America. More men are affected than women.
• The direct cause of gastric cancer is not clear, but Helicobacter pylori infection and some hereditary cancer predisposition syndromes may play a role.
• Patients often present with nonspecific symptoms which may include anorexia, weight loss, abdominal pain, dyspepsia, vomiting, and early satiety.

Evaluation

• For initial testing to establish diagnosis:
  • Perform a complete history and physical exam (Strong recommendation).
  • The confirmation of diagnosis is based on upper gastrointestinal endoscopy and biopsy (Weak recommendation).
• For the initial workup aimed at staging and pretreatment planning:
  • Perform endoscopy (Strong recommendation) and consider assessment of Siewert category (Weak recommendation).
  • Consider biopsy
    • with endoscopic resection for T1a or T1b disease (Weak recommendation) when lesions are ≤ 2 cm.
    • of metastases if it is clinically indicated (Weak recommendation).
  • Perform computed tomography (CT) (with oral and IV contrast) of the chest/thorax, abdomen, and pelvic region (Strong recommendation).
  • Perform blood tests including complete blood count with differential, liver and renal function tests (Strong recommendation), and comprehensive chemistry profile (Weak recommendation).
  • Consider endoscopic ultrasound in patients with suspected early stage disease, or if it is necessary to differentiate between early and locally advanced disease (Weak recommendation).
  • If metastases are not evident from other staging methods (cM0), additional workup may include:
    • positron emission tomography (PET)/CT from skull base to midthigh if it is clinically indicated (Weak recommendation) to confirm lymph node involvement or distant metastases
    • laparoscopy with cytology in patients with ≥ cT1b disease (Weak recommendation) to evaluate peritoneal spread when considering nonpalliative surgery or chemoradiation therapy
• Genetic testing for patients with suspected or confirmed locally advanced, recurrent, or metastatic disease:
  • In patients with inoperable disease, if trastuzumab therapy is being planned, test for human epidermal growth factor receptor 2 (HER2) expression (Weak recommendation).
  • If treatment with program cell death 1 (PD-1) inhibitors is being planned, test for microsatellite instability (MSI) or DNA mismatch repair (MMR) and program cell death ligand 1 (PD-L1) expression (Weak recommendation).
• Consider an evaluation with a multidisciplinary team (Weak recommendation), which may include
  • surgical, medical, and radiation oncologists, gastroenterologists, radiologists, and pathologists
  • supportive disciplines, such as nutritional services, social workers, nursing, and palliative care specialists

Management

Management of nonmetastatic disease

• Primary treatment
  • For patients with cTis or cT1a disease, consider either endoscopic resection (Weak recommendation) followed with endoscopic surveillance (Weak recommendation), or upfront gastrectomy with lymphadenectomy (Weak recommendation) if major surgery is tolerable, followed with adjuvant treatment.
  • For patients with ≥ cT2, any N disease that is resectable, and major surgery is tolerable, options include:
    • Offer perioperative chemotherapy (Strong recommendation) or consider neoadjuvant chemoradiation (Weak recommendation), followed with a treatment response assessment with chest/abdomen/pelvic computed tomography (CT) with contrast (Weak recommendation) and appropriate follow-up treatment based on treatment response.
    • Consider upfront gastrectomy with lymphadenectomy (Weak recommendation) followed with adjuvant treatment.
  • For patients with unresectable disease, options include initial chemoradiation or systemic chemotherapy (Weak recommendation) with follow-up treatment, or palliative management.
  • For patients who refuse or are unable to tolerate major surgery, options include definitive chemoradiation (Weak recommendation) with follow-up treatment, or palliative management.
• Adjuvant treatment after resection depends on the resection margins, pathologic stage, and receipt of neoadjuvant therapy; options may include chemotherapy, chemoradiation, re-resection, or palliative management.
• Follow-up treatment after initial or definitive chemoradiation depends on the disease status after restaging:
  • If the disease is converted to resectable disease, and it is medically operable, consider gastrectomy with lymphadenectomy (preferred) or surveillance (Weak recommendation).
  • If the disease remains unresectable or it is medically inoperable, and/or if there is evidence of metastases, consider palliative management (Weak recommendation).

Management of locally advanced, recurrent, or metastatic disease

• Consider enrollment in clinical trials, especially in unresectable locally advanced, recurrent, or metastatic disease, if patients are medically fit (Weak recommendation).
• For locoregional recurrence that is resectable and medically operable, consider gastrectomy with lymphadenectomy (Weak recommendation), or options from management of unresectable locally advanced, recurrent, or metastatic disease.
• For unresectable locally advanced, recurrent, or metastatic disease, treatment depends on the patient's performance status:
  • If Karnofsky performance score (PS) is ≥ 60% or Eastern Cooperative Oncology Group (ECOG) PS is ≤ 2, options include chemoradiation (if not previously given, and for locally unresectable disease only), systemic chemotherapy, or best supportive care (Weak recommendation).
  • If Karnofsky PS is < 60%, or ECOG PS is ≥ 3, consider best supportive care (Weak recommendation).

Surveillance

• Regular follow-up may help detection and management of symptoms, offer psychological support, and detect disease recurrence, but there is no evidence that shows improved survival with follow-up (Weak recommendation).
• Follow-up strategies vary based on disease stages and individual patients (Weak recommendation).