What is the initial treatment for a patient with Gastrointestinal Stromal Tumor (GIST)?

Initial Treatment for Gastrointestinal Stromal Tumor (GIST)

Complete surgical resection (R0) is the standard initial treatment for localized, resectable GIST, with the goal of achieving negative margins while preserving organ function. 1

Diagnostic Evaluation Before Treatment

Before proceeding with treatment, proper diagnosis and evaluation are essential:

• CT scan of abdomen and pelvis with contrast is the imaging modality of choice for diagnosis and staging 1
• Diagnosis confirmation requires CD117 (KIT) and/or DOG1 immunopositivity 1, 2
• Mutational analysis of KIT and PDGFRA is essential for confirming diagnosis and guiding treatment decisions 1
• For gastric and small intestinal lesions, endoscopic ultrasonography (EUS) is recommended 1
• For rectal GISTs, MRI provides better preoperative staging 1

Treatment Approach Based on Tumor Size

Small GISTs (<2 cm)

• Gastric GISTs: Can be managed with either active surveillance or resection based on risk characteristics 1
• Rectal GISTs: Should be resected regardless of size 1

GISTs ≥2 cm

• Complete surgical resection (R0) without lymph node dissection is the standard approach 1
• Segmental resection of intestine and stomach is acceptable 1
• Extensive surgery to remove unaffected tissue is unnecessary 1

Surgical Techniques

The surgical approach depends on tumor location:

• Gastric GIST: Wedge resection is recommended 1
• Intestinal GIST: Segmental resection 1
• Esophageal, duodenal, and rectal GISTs: Wide resection 1
• Laparoscopic approach: Safe for gastric GISTs ≤5 cm, using a plastic bag to extract the specimen 1

Important caveat: Direct handling of tumors with forceps during laparoscopy should be avoided to prevent tumor rupture, which significantly worsens prognosis 1

Neoadjuvant Therapy Considerations

For certain cases, preoperative imatinib may be considered before surgical resection:

• Marginally resectable tumors
• Cases where surgical morbidity would be improved by reducing tumor size
• Large tumors likely to require multivisceral resection 1

When using preoperative imatinib:

• Continue until maximal response (typically 6-12 months)
• Perform surgery after significant response but before progression 1
• Mutational analysis should be performed before starting treatment 1

Adjuvant Therapy After Resection

After complete resection, adjuvant therapy decisions are based on risk assessment:

• High-risk patients: Adjuvant imatinib for 3 years is recommended 1
• Risk factors include: large tumor size, high mitotic rate, non-gastric location, and tumor rupture 1
• Important exception: Adjuvant therapy should not be used for tumors with PDGFRA exon 18 D842V mutation due to resistance 1

Treatment of Unresectable or Metastatic GIST

For patients with unresectable or metastatic disease:

• Imatinib mesylate is the standard first-line therapy (400 mg daily) 1, 3
• For KIT exon 9 mutations, a higher dose of 800 mg daily may be more effective 1
• Treatment should continue indefinitely until disease progression or unacceptable toxicity 1
• For imatinib-resistant disease, subsequent options include sunitinib and regorafenib 4, 3

Follow-up and Surveillance

After treatment, regular imaging surveillance is recommended:

• Risk-stratified approach, with higher-risk patients requiring more intensive follow-up 1
• CT abdomen and pelvis with contrast is the method of choice 1
• First follow-up within 6 months, then more relaxed if stable 1

Key Pitfalls to Avoid

1. Tumor rupture: Avoid at all costs during surgery as it significantly worsens prognosis and increases risk of peritoneal relapse 1
2. Inadequate mutation testing: Always perform mutational analysis before starting targeted therapy 1
3. Unnecessary lymphadenectomy: Not routinely necessary as lymph node metastases are rare (except in SDH-mutated GISTs) 1
4. Delayed treatment decisions: Multidisciplinary discussion is essential for optimal management 5