What preoperative evaluation and management are recommended for a patient with Gastrointestinal Stromal Tumor (GIST) syndrome being considered for surgery?

Preoperative Evaluation for GIST Surgery

All patients with GIST being considered for surgery must undergo multidisciplinary team evaluation with sarcoma expertise, comprehensive staging with contrast-enhanced CT abdomen/pelvis and chest imaging, endoscopic assessment if not previously performed, and surgical risk assessment to determine resectability and need for neoadjuvant imatinib. 1

Essential Preoperative Workup Components

Imaging Studies

• Contrast-enhanced CT scan of abdomen and pelvis is the preferred imaging modality to characterize the tumor, evaluate extent, and assess for metastases 1
• Chest imaging (CT preferred) to evaluate for pulmonary metastases 1
• PET scan may be obtained to clarify ambiguous CT/MRI findings and differentiate active tumor from necrotic tissue, but is not a substitute for CT 1
• If PET will be used for monitoring therapy response, obtain baseline PET before starting treatment 1

Endoscopic Evaluation

• Endoscopy if not previously performed to visualize the tumor 1
• Endoscopic ultrasound (EUS) in selected patients to assess local extent and tumor characteristics 1, 2
• EUS-guided biopsy is preferred over percutaneous biopsy if tissue diagnosis is needed 1

When Biopsy Is Required

Biopsy should be performed if preoperative imatinib therapy is being considered for unresectable or marginally resectable tumors 1. However, biopsy may not be necessary if the tumor is easily resectable and preoperative therapy is not required 1.

The pathology report must include:

• Anatomic location and tumor size 1
• Mitotic rate measured in the most proliferative area, reported as number of mitoses per 50 high power fields 1
• Immunohistochemical staining for KIT (CD117) and CD34 1
• Molecular genetic testing for KIT and PDGFRA mutations 1

Surgical Risk Assessment and Decision Algorithm

For Easily Resectable Tumors (≥2 cm)

Proceed directly to surgery without neoadjuvant therapy if the tumor can be resected with minimal morbidity 1. Surgery is the primary treatment for all patients with resectable GISTs of 2 cm or greater who have no significant risk for morbidity 1.

For Marginally Resectable or High Surgical Morbidity Cases

Consider preoperative imatinib if surgical morbidity would be improved by reducing tumor size 1. Specific indications include:

• Complex multivisceral resection would be required 1
• Rectal GIST requiring abdominoperineal resection to achieve negative margins 1
• Gastroesophageal junction GIST where esophagus-sparing surgery is desired 1
• Large tumors where downsizing would allow less invasive procedures 3, 4

Critical caveat: Close monitoring is essential during neoadjuvant therapy because some patients may become unresectable rapidly 1. Surgery is recommended immediately if bleeding and/or severe symptoms develop 1.

Preoperative Imatinib Protocol

If neoadjuvant imatinib is chosen:

• Obtain baseline CT with or without MRI before starting imatinib 1
• Continue imatinib until maximal response (no further improvement between 2 successive CT scans, which can take 6-12 months) 1
• Perform mutational analysis before starting therapy to exclude imatinib-resistant disease, particularly PDGFRA D842V mutations 3
• Reassess within 3 months of initiating therapy to determine if tumor has become resectable 1
• If progression occurs on imatinib, discontinue and proceed to surgery if feasible 1

For Unresectable or Metastatic Disease

Patients with documented unresectable GIST, risk for severe functional deficit after resection, or widespread metastatic disease should be treated with imatinib 400 mg daily 1, 5. Reassess for resectability after response to therapy 1.

General Medical Fitness Assessment

Cardiac Evaluation

• ECG and echocardiography to assess cardiac function 6
• This is particularly important as severe congestive heart failure and left ventricular dysfunction have been reported with imatinib, especially in patients with comorbidities 5

Laboratory Assessment

• Complete blood counts as cytopenias (anemia, neutropenia, thrombocytopenia) can occur with imatinib 5
• Liver function tests as severe hepatotoxicity may occur with imatinib 5
• Standard preoperative laboratory evaluation 6

Hepatic Impairment Considerations

If imatinib is planned:

• Mild to moderate hepatic impairment: 400 mg/day 5
• Severe hepatic impairment: 300 mg/day 5

Key Surgical Planning Principles

The surgical goal is complete gross resection with intact pseudocapsule while avoiding tumor rupture 1. Specific considerations:

• Segmental or wedge resection is often appropriate; extended anatomic resections (total gastrectomy) are rarely indicated 1
• Lymphadenectomy is usually not required given low incidence of nodal metastases 1
• Laparoscopic approach may be considered for favorable anatomic locations (anterior gastric wall, jejunum, ileum) by experienced surgeons 1
• Tumor rupture significantly increases peritoneal recurrence risk and must be avoided 3