The desmoids in FAP are often intra-abdominal, may present early, and can lead to intestinal obstruction or infarction and/or obstruction of the ureters. In some series, desmoids are the second most common cause of death after CRC in FAP patients.[38,39] A staging system has been proposed to facilitate the stratification of intra-abdominal desmoids by disease severity. The proposed staging system for intra-abdominal desmoids is as follows: stage I for asymptomatic, nongrowing desmoids; stage II for symptomatic, nongrowing desmoids of 10 cm or less in maximum diameter; stage III for symptomatic desmoids of 11 to 20 cm or for asymptomatic, slow-growing desmoids; and stage IV for desmoids larger than 20 cm, or rapidly growing, or with life-threatening complications.
These data suggest that genetic testing could be of value in the medical management of patients with FAP and/or multiple desmoid tumors. Those with APC genotypes, especially those predisposing to desmoid formation (e.g., at the 3' end of APC codon 1445), appear to be at high risk of developing desmoids following any surgery, including risk-reducing colectomy and surgical surveillance procedures such as laparoscopy.[28,35,41]
The management of desmoids in FAP can be challenging and can complicate prevention efforts. Currently, there is no accepted standard treatment for desmoid tumors. Multiple medical treatments have generally been unsuccessful in the management of desmoids. Treatments have included antiestrogens, nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapy, and radiation therapy, among others. Studies have evaluated the use of raloxifene alone, tamoxifen or raloxifene combined with sulindac, and pirfenidone alone.[42,43,44] There are anecdotal reports of using imatinib mesylate to treat desmoid tumors in FAP patients; however, further studies are needed. Significant desmoid tumor regression was reported in seven patients who had symptomatic, unresectable, intra-abdominal desmoid tumors and failed hormonal therapy when treated with chemotherapy (doxorubicin and dacarbazine) followed by meloxicam.
Thirteen patients with intra-abdominal desmoids and/or unfavorable response to other medical treatments, who had expression of estrogen alpha receptors in their desmoid tissues, were included in a prospective study of raloxifene, given in doses of 120 mg daily. Six of the patients had been on tamoxifen or sulindac before treatment with raloxifene, and seven patients were previously untreated. All 13 patients with intra-abdominal desmoid disease had either a partial or a complete response 7 months to 35 months after starting treatment, and most desmoids decreased in size at 4.7 � 1.8 months after treatment. Response occurred in patients with desmoid plaques and with distinct lesions. Study limitations include small sample size, and the clinical evaluation of response was not consistent in all patients. Several questions remain concerning patients with desmoid tumors not expressing estrogen alpha receptors who have received raloxifene and their outcome and which patients may benefit from this potential treatment.