What is the optimal treatment option for mesenteric desmoid tumors in patients with Familial Adenomatous Polyposis (FAP)?

Optimal Treatment for Mesenteric Desmoid Tumors in FAP Patients

The optimal first-line treatment for mesenteric desmoid tumors in FAP patients is sulindac (300 mg daily) combined with high-dose selective estrogen receptor modulators such as tamoxifen (40-120 mg daily), toremifene (180 mg), or raloxifene (120 mg), with surgery reserved only for life-threatening complications or secondary effects. 1

Treatment Algorithm

Initial Management Approach

• Observation with serial imaging (CT or MRI every 6-12 months) is appropriate for asymptomatic mesenteric desmoids without secondary effects, as some tumors spontaneously stabilize or regress 1
• Medical therapy should be initiated for large, growing, or symptomatic tumors 1

First-Line Medical Therapy

• Sulindac 300 mg daily combined with tamoxifen 40-120 mg daily (or toremifene 180 mg or raloxifene 120 mg) represents the standard first-line treatment 1
• This combination achieves partial or complete regression in approximately 77% of FAP-associated mesenteric desmoids when used as primary treatment 2
• Response assessment should occur every 6 months with cross-sectional imaging 2

Second-Line Options for Progressive Disease

• For tumors that progress despite NSAIDs plus hormonal therapy, chemotherapy with methotrexate and vinblastine OR doxorubicin-based regimens should be considered 1
• Chemotherapy demonstrates the highest response rate (77%) among all treatment modalities for mesenteric desmoids 3
• The combination of dacarbazine and doxorubicin has shown dramatic responses even in extremely aggressive, life-threatening mesenteric desmoids, achieving near-complete regression 4

Role of Surgery

• Elective surgery for intra-abdominal/mesenteric desmoids should be restricted to treating secondary effects (ureteric obstruction, bowel obstruction, ischemia, fistula formation) 1
• Surgery carries high recurrence rates and should only be performed at expert centers 1
• The British Society of Gastroenterology (2020) provides a strong recommendation against routine surgical excision of mesenteric desmoids due to poor outcomes 1

Role of Radiotherapy

• Radiotherapy is indicated only for progressive intra-abdominal tumors that fail medical therapy and are not surgically resectable 1
• Radiation is now rarely used for intra-abdominal desmoids due to severe late toxicity 5

Critical Distinctions

The location of the desmoid fundamentally determines treatment strategy 1:

• Mesenteric/intra-abdominal desmoids: Medical therapy first, surgery only for complications
• Abdominal wall desmoids: Surgery is more appropriate with better outcomes and lower recurrence rates 6

Evidence Quality and Nuances

The 2020 British Society of Gastroenterology guidelines provide the most recent and comprehensive recommendations, achieving 95-100% consensus on key management principles 1. The ESMO 2013 guidelines similarly recommend sulindac plus tamoxifen as first-line therapy 1.

Important caveats:

• The evidence base consists primarily of small, non-controlled studies with very low to low-grade evidence 1
• Despite limited evidence quality, there is strong consensus against routine surgery for mesenteric desmoids due to consistently poor outcomes across multiple studies 1
• Chemotherapy, while showing the highest response rates (77%), should be reserved for second-line treatment due to toxicity concerns 3

Answer to Multiple Choice Question

The correct answer is A: Tamoxifen (plus NSAIDs +/- doxorubicin, vinblastine) 1

This option encompasses the guideline-recommended first-line therapy (NSAIDs + tamoxifen) and appropriate second-line chemotherapy options. Cortisone has no established role, radiotherapy is rarely used due to toxicity, and methotrexate alone (without vinblastine) is not the optimal regimen 1, 5.