What is the recommended treatment plan for an older adult patient diagnosed with gastric cancer?

Treatment Plan for Older Adult Patients with Gastric Cancer

For older adults with gastric cancer, treatment decisions must be guided by disease stage, resectability, performance status, and molecular biomarkers, with perioperative chemotherapy plus surgery as the standard for resectable disease and biomarker-directed systemic therapy for metastatic disease. 1

Initial Diagnostic Workup and Staging

• Complete staging must include endoscopy with biopsy to confirm adenocarcinoma histology, determine Lauren classification, and obtain tissue for HER2 testing if metastatic disease is suspected 1
• Contrast-enhanced CT of thorax, abdomen, and pelvis is mandatory to detect lymphadenopathy, metastatic disease, and assess resectability 1
• Laparoscopy with peritoneal washings is essential for all stage IB-III cancers to exclude occult peritoneal metastases not visible on imaging, as imaging misses peritoneal disease in a significant proportion of patients 1, 2
• Blood tests including complete blood count, liver and renal function tests are necessary 2
• Endoscopic ultrasound may help optimally determine resectability 2

Multidisciplinary Team Evaluation

• All treatment decisions must be made by a multidisciplinary team including surgeons, medical oncologists, radiation oncologists, gastroenterologists, radiologists, pathologists, dieticians, and nurse specialists before proceeding with any treatment 2, 1

Stage-Specific Treatment Algorithm

Very Early Disease (T1a)

• Endoscopic resection alone is appropriate if all criteria are met: confined to mucosa, well-differentiated histology, non-ulcerated, ≤2 cm diameter, and no lymphovascular invasion 1
• However, endoscopic resection is contraindicated for signet ring cell carcinoma even if small, as these lesions are characteristically multifocal throughout the stomach 3

Localized Resectable Disease (Stage IB and Above)

• Perioperative chemotherapy followed by surgery followed by completion of chemotherapy is the standard of care 1, 2
• Preoperative chemotherapy consists of 3 cycles of ECF (epirubicin 50 mg/m², cisplatin 60 mg/m², continuous infusion 5-fluorouracil 200 mg/m²/day) or ECX (capecitabine substituted for 5-FU) regimen 2, 1
• Surgery with D2 lymphadenectomy should be performed after preoperative chemotherapy, with distal gastrectomy appropriate for antral tumors and total gastrectomy for proximal lesions 1
• Resection margins must achieve ≥3 cm for Borrmann I-II tumors and ≥5 cm for Borrmann III-IV tumors 1
• A minimum of 14 lymph nodes, optimally at least 25, must be examined pathologically for accurate staging 3
• Postoperative chemotherapy completes the remaining 3 cycles of the same regimen 1
• This perioperative approach improved 5-year survival from 23% to 36.3% in the landmark MAGIC trial 2, 1

Important Surgical Considerations

• Splenectomy should not be performed unless the tumor directly invades the spleen, as it increases complications without survival benefit 1
• D2 lymphadenectomy involves removal of perigastric nodes and nodes along celiac arterial branches 1
• Do not accept inadequate lymph node evaluation (fewer than 14 nodes examined), as this leads to understaging and suboptimal treatment planning 3

Locally Advanced Unresectable Disease

• Concurrent chemoradiotherapy is recommended for patients with good performance status (ECOG 0-1) and unresectable locally advanced disease 2
• Chemotherapy options for concurrent chemoradiation include: capecitabine + paclitaxel, cisplatin + fluoropyrimidine (5-FU, capecitabine, or S-1), or oxaliplatin + fluoropyrimidine 2
• After concurrent chemoradiotherapy, the multidisciplinary team should re-evaluate tumor resectability, and surgery can be considered if complete resection is achievable 2
• For patients unsuitable for concurrent chemoradiotherapy due to extensive tumor or poor performance status (ECOG 2), best supportive care or symptomatic treatment is appropriate 2

Metastatic Disease (Stage IV)

• HER2 testing must be performed on all metastatic gastric adenocarcinomas using FDA-approved tests specifically for gastric cancers, as gastric cancer has different histopathology than breast cancer including incomplete membrane staining and more frequent heterogeneous HER2 expression 4

HER2-Positive Metastatic Disease

• For HER2-positive tumors, trastuzumab must be added to first-line platinum/fluoropyrimidine doublet chemotherapy (cisplatin plus capecitabine or 5-fluorouracil) 4, 1
• Trastuzumab dosing: initial dose 8 mg/kg IV over 90 minutes, then 6 mg/kg IV every 3 weeks 4
• Evaluate left ventricular ejection fraction (LVEF) prior to initiation and at regular intervals during treatment, as trastuzumab can cause cardiomyopathy 4

HER2-Negative Metastatic Disease

• First-line palliative combination chemotherapy should be offered to patients with good performance status 1, 2
• Preferred first-line regimen: FLOT (docetaxel, oxaliplatin, leucovorin, 5-FU) 5
• Alternative first-line regimens: ECF or ECX, or docetaxel + cisplatin + fluorouracil 1, 5
• For PD-L1 CPS ≥5 tumors, nivolumab combined with chemotherapy is recommended 5
• For MSI-H/dMMR tumors, pembrolizumab or dostarlimab-gxly should be considered 5

Special Considerations for Older Adults

• For patients with poor performance status (ECOG ≥2), best supportive care alone is appropriate rather than chemotherapy 2, 3
• Nutritional status must be maintained throughout treatment, with active prevention and timely treatment of complications such as bleeding, obstruction, or perforation 2
• Palliative interventions including bypass surgery, endoscopic treatment, stenting, or palliative radiotherapy are recommended if they may improve nutritional status or alleviate bleeding, pain, or obstruction 2

Critical Pitfalls to Avoid

• Do not proceed to surgery without laparoscopy in potentially resectable stage IB-III disease, as imaging misses peritoneal metastases in a significant proportion of patients 1, 3
• Do not perform routine splenectomy, as it increases morbidity without oncologic benefit 1
• Do not accept inadequate lymph node evaluation, as this leads to understaging and suboptimal treatment planning 1, 3
• Do not attempt endoscopic resection for signet ring cell carcinoma even for small lesions, as multifocal disease is characteristic 3
• Do not use HER2 testing protocols designed for breast cancer when evaluating gastric cancer, as gastric cancer requires specific FDA-approved tests due to different histopathology 4
• Do not proceed directly to surgery for porta hepatis lymph node involvement, as this represents Level 3-4 lymph nodes indicating unresectable disease requiring systemic chemotherapy 5

Follow-Up After Curative Treatment

• Symptom-driven visits are recommended rather than intensive routine surveillance, as regular intensive follow-up does not improve outcomes 1, 2
• History, physical examination, and blood tests should be performed if symptoms of relapse occur 2
• Radiological investigations should be considered only for patients who are candidates for palliative chemotherapy 2