What is the diagnosis and treatment for a Gastrointestinal Stromal Tumor (GIST) located in the rectum?

From the Guidelines

Rectal GISTs should be managed with a multidisciplinary approach, with surgery considered for all cases, regardless of size, and a tailored surgical strategy based on the precise anatomic site and size of the tumor. The management of rectal GIST is complex, and a multidisciplinary approach is particularly helpful in these cases 1. All suspected rectal GISTs should be biopsied and preferably excised after EUS assessment, regardless of tumor size, due to the higher risk of recurrence and critical local implications for surgery.

Key Considerations

• Dedicated rectal MRI and examination under anesthesia may be considered for initial assessment 1
• Surgical strategy should be tailored to the precise anatomic site and size of the tumor, considering the relation to the sphincter complex 1
• Organ-preserving approaches, such as pararectal incisions, transanal approaches, and minimally invasive surgery, should be considered when possible 1
• Neoadjuvant therapy with imatinib may be considered for larger tumors to facilitate a more marginal excision, especially when the tumor demonstrates response to imatinib 1

Treatment Approach

• Complete surgical resection with negative margins is the gold standard treatment, which may involve local excision for small tumors or more extensive procedures like abdominoperineal resection for larger lesions 1
• Targeted therapy with imatinib is recommended for unresectable or metastatic disease, starting at 400mg daily 1
• Risk stratification based on tumor size, mitotic rate, and location guides adjuvant therapy decisions, with high-risk patients typically receiving adjuvant imatinib for 3 years 1

Multidisciplinary Management

• Multidisciplinary team management involving surgical oncology, medical oncology, and gastroenterology provides optimal outcomes for these challenging tumors 1
• Long-term surveillance with regular imaging is necessary, as recurrences can occur even years after initial treatment 1

From the FDA Drug Label

The primary objective of the two studies was to evaluate either progression-free survival (PFS) with a secondary objective of overall survival (OS) in one study or overall survival with a secondary objective of PFS in the other study. A planned analysis of both OS and PFS from the combined datasets from these two studies was conducted. All patients had a pathologic diagnosis of CD117 positive unresectable and/or metastatic malignant GIST

The FDA drug label does not answer the question about Rectal GIST.

From the Research

Overview of Rectal GIST

• Rectal GIST is a rare entity, accounting for approximately 5% of all GISTs 2
• Symptoms of rectal GIST include bleeding, pain, and occasionally urinary symptoms 2
• Immunohistochemical evaluation finds that most rectal GIST tumors are CD117 (KIT) positive, and are sometimes CD34, platelet-derived growth factor receptor alpha (PDGFRA), smooth muscle actin, S-100, or vimentin positive 2

Treatment Strategies

• The first-line treatment for localized GIST is curative resection, but is difficult in rectal GIST due to anatomical characteristics 2
• Minimally invasive surgery, such as trans-anal, trans-sacral, trans-vaginal resection, or laparoscopic resection, may be effective for rectal GIST 2, 3
• Imatinib mesylate (IM) is indicated as first-line treatment of metastatic or unresectable GIST, and clinical outcomes are correlated with KIT mutation genotype 2, 3
• Peri-operative IM therapy may improve postoperative outcomes and contribute to anus-preserving surgery 3
• KIT mutation analysis before IM treatment is important 2

Risk Stratification and Management

• The National Institutes of Health (NIH) classifies rectal GIST as very-low risk, low risk, intermediate risk, or high risk 2
• Positive resection margin is an important hazard factor for disease-free survival (DFS) 3
• Among patients with intermediate and high-risk tumors, those who received peri-operative Imatinib therapy had longer DFS compared with those without 3
• The location of rectal GIST impacts the choice of resection type, with most patients with tumors within 5 cm of the anal verge able to be treated with local excision 3

Multidisciplinary Approach

• The decision to pursue metastasectomy for GIST should be made in a multidisciplinary setting and be individualized according to patient age, comorbidities, functional status, symptoms, mutation status, extent of disease, completeness of resection, TKI response, and goals of the patient 4
• A careful multidisciplinary consultation is required to determine optimal treatment options on a case-by-case basis 5