Desmoid tumors: Treatment

INTRODUCTION — 

Desmoid tumors (also called aggressive fibromatosis, deep musculoaponeurotic fibromatosis, and fibrosarcoma grade I of the desmoid type) are locally aggressive tumors with no known potential for metastasis or dedifferentiation. However, tumor invasion into vital structures and/or organs can result in substantial morbidity and may be fatal, especially in the case of intra-abdominal desmoids, particularly those arising in patients with familial adenomatous polyposis (FAP).

Desmoid tumors can follow an unpredictable clinical course, with some tumors undergoing regression in the absence of therapy. For many patients, especially those with asymptomatic or minimally symptomatic tumors, an initial strategy of active surveillance is the preferred approach. However, if a desmoid tumor progresses on serial imaging or is associated with significant symptoms that are difficult to manage, a multidisciplinary team should determine the best individualized approach. Although surgery and radiation had traditionally been used, systemic therapy is often preferred for many patients, including those with FAP or intra-abdominal/mesenteric tumors, when an intervention is required.

This topic review will discuss treatment options for desmoid tumors. The epidemiology, clinical presentation, and diagnosis of desmoids are discussed elsewhere. (See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, and diagnosis".)

ASYMPTOMATIC OR MINIMALLY SYMPTOMATIC PATIENTS

Initial surveillance — In patients with newly diagnosed desmoid tumors, we pursue active surveillance as the initial management unless patients have moderate or severe symptoms that cannot be controlled with appropriate supportive care (eg, nonsteroidal anti-inflammatory agents [NSAIDs] or acetaminophen) or further progression of the tumor would cause significant morbidity (eg, threatens a limb or vital organ). Active surveillance typically involves imaging studies at least every three to six months. We typically will obtain our first imaging at three months after diagnosis to determine the growth rate. This approach is consistent with consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) [1]. However, the development of symptoms in a previously asymptomatic or minimally symptomatic patient should prompt earlier evaluation with imaging and initiation of therapy. (See 'Symptomatic patients' below.)

Support for observation as a treatment strategy is supported in several studies. As an example, in a phase III trial comparing the use of sorafenib with placebo in patients with desmoid fibromatosis, 20 percent of patients in the placebo arm had a partial response [2].

Similarly, in a report of 106 primary abdominal wall desmoid tumors initially managed without surgery (4 with medical treatment and 102 with initial observation only), the one- and three-year incidences of a final switch to surgery were 14 and 16 percent, respectively [3]. Of the 102 patients who were initially observed, 29 experienced spontaneous tumor regression over a median follow-up period of 32 months. Additionally, in one series of 54 patients with a primary or recurrent desmoid who were not treated initially with surgery, radiation therapy (RT), or systemic therapy, the five-year progression-free survival rate was 50 percent [4].

These data suggest the importance of observation, especially in patients in whom symptoms are mild or absent. However, approximately 50 percent of patients will develop progression within five years while on surveillance [4].

SYMPTOMATIC PATIENTS

Approach to management — In patients who are symptomatic or develop progression across sequential imaging studies, multidisciplinary input should determine which treatment modality is best for the individual. The decision about which treatment modality to use takes into consideration the location of the tumor, whether it is associated with familial adenomatous polyposis (FAP), potential toxicity of therapies, and the desired urgency of response. We use the following as a guide for management:

●In situations such as bowel obstruction or impending threat to life, we suggest surgery. Similarly, for most patients with a sporadic desmoid located in the abdominal wall, we suggest initial treatment with surgery. However, if the patient is not a surgical candidate, then radiation or systemic therapy may be acceptable alternatives, but the time course must be considered, particularly in patients with urgent presentations. Systemic therapy may afford a response over a period of several weeks to months, while radiation may take longer.

●If the patient is symptomatic with a FAP-associated desmoid or a sporadic nonabdominal wall desmoid, but no imminent threat to life or significant morbidity, we suggest systemic therapy. However, local therapy may be an option in certain patients such as those who want to avoid the toxicity of systemic agents.

●For patients with diffuse infiltration into the mesentery, we suggest systemic therapy.

Sporadic abdominal wall desmoid

Surgery — In patients with sporadic (non-FAP-associated) desmoid located in the abdominal wall, we suggest initial treatment with surgery. However, resection of abdominal wall desmoids may require reconstruction of the abdominal wall to close the defect and minimize the risk of hernias. Medical therapy is an alternative for patients who do not wish to undergo surgery or the surgery is associated with a high risk of morbidity. However, resection does not appear to affect survival, so a decision about surgery should be made with multidisciplinary input and a discussion about individual risks and benefits.

When surgery is indicated, complete resection of the tumor with negative microscopic margins is the standard goal, but positive margins are acceptable if necessary to maintain function [5,6]. The overall surgical strategy should also use function-preserving surgical approaches to minimize major morbidity (functional and/or cosmetic). Truly radical resections are not indicated.

Desmoid tumors have a high rate of recurrence following complete surgical removal, and the contribution of incomplete resection to local recurrence rates is unclear [5,7-14]. While some series [5,8,10,12,13,15,16] show higher recurrence rates with close or positive resection margins, many series report that the risk of recurrence is independent of margin status [7,17-22]. As an example, in one of the largest series of over 400 patients with newly diagnosed desmoid tumors, the five-year progression-free survival (PFS) was similar for patients who had an R0 or R1 resection (63 versus 61 percent) [23]. However, a difference in the five-year PFS was evident when comparing those who had an R0 or R1 resection with those who only received an R2 resection (22 percent).

These data, combined with the fact that recurrence only develops in fewer than one-half of those with positive margins [13], have led some to conclude that aggressive attempts to achieve negative resection margins are not warranted if they result in excessive morbidity [13,17,24,25]. Systemic therapy is often preferred for tumor control in situations when surgery would result in excessive morbidity.

No role for adjuvant radiation therapy — We do not offer adjuvant radiation for patients with either microscopically positive margins or those with gross or macroscopic residual disease [10,26]. Typically, we suggest surveillance rather than radiation after surgery, given the risk of secondary malignancies, limited data about the impact of radiation therapy, and unclear benefit of achieving a complete resection [5,7,9,17,18].

In a meta-analysis of 16 retrospective reviews including over 1000 patients, adjuvant RT was associated with improved recurrence rates after incomplete surgical resection for patients with primary extra-abdominal and abdominal wall tumors (risk ratio [RR] 1.54, 95% CI 1.05-2.27) and in those with recurrent disease (RR 1.60, 95% CI 1.12-2.28) [14]. However, the lack of randomization in any of these reports and the missing information on tumor size and anatomic location compromise interpretation of the results.

Sporadic nonabdominal wall and FAP associated desmoids — In patients with a nonabdominal wall or a FAP-associated desmoid, we suggest initial medical therapy. However, if there is a bowel obstruction or impending threat to life, we pursue urgent evaluation for surgery. (See 'Surgery' above.)

In general, nirogacestat is the preferred systemic therapy option. Tyrosine kinase inhibitors (TKI) are also reasonable options. However, cytotoxic chemotherapy is preferred for patients needing a more rapid response or if there are concerns about absorption of oral medications. In patients for whom systemic therapy is contra-indicated, local therapy options such as surgery, radiation, or cryoablation are alternatives. However, treatments are individualized and a final treatment plan should be developed with multidisciplinary input. (See 'Alternative therapies' below.)

Nirogacestat (preferred) — Nirogacestat, an oral gamma secretase inhibitor that targets the Notch pathway, is an effective treatment for locally aggressive or symptomatic desmoid tumors. For patients with moderate symptoms, we prefer nirogacestat over a TKI, hormone therapy, or chemotherapy. Although nirogacestat has been shown to cause ovarian dysfunction, this resolves upon discontinuation for the majority of patients [27]. However, we do not have long-term data about the duration and ultimate frequency of resumption of menstrual cycles after discontinuation of nirogacestat. We do not consider desire for future childbearing to be a contraindication to use of this agent; however, some patients who desire future childbearing may elect for an alternative strategy such as a TKI, or may elect to pursue egg harvesting before initiation of treatment.

In a placebo-controlled randomized trial, among 142 patients with progressive desmoid tumors, nirogacestat improved PFS (median not reached versus 15 months; hazard ratio [HR] 0.29, 95% CI 0.15-0.55), objective response rate (41 versus 8 percent), and complete responses rates (7 versus 0 percent), at median follow-up of 19 months [28]. Nirogacestat also improved tumor-related symptom burden, pain, physical/role functioning, and health-related quality of life.

Grade ≥3 toxicities for nirogacestat included diarrhea (16 percent), maculopapular rash (6 percent), stomatitis (4 percent), fatigue and hypophosphatemia (3 percent each), and nausea (1 percent). These adverse events generally respond to dose reduction without unduly sacrificing clinical activity.

Ovarian dysfunction occurred in 75 percent of females of child-bearing potential. Most patients (74 percent) with ovarian dysfunction had resolution based on hormonal levels and/or symptoms while receiving nirogacestat or after stopping for any reason.

The United States Food and Drug Administration has approved nirogacestat for patients with progressing desmoids who require systemic treatment [29].

Tyrosine kinase inhibitors — TKIs are appropriate for patients who require systemic therapy, but who do not tolerate or progress on nirogacestat or have concerns about ovarian dysfunction. Although comparative studies are lacking, if a TKI is chosen for treatment, we suggest sorafenib, pazopanib, or sunitinib rather than imatinib, given the greater degree of activity seen with these broader-spectrum, albeit more toxic, TKIs. However, imatinib is an acceptable alternative for those who may not be able to tolerate the other TKIs.

●Sorafenib – The benefit of sorafenib, a multitargeted TKI that inhibits the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase, was confirmed in a randomized, placebo-controlled trial in 87 patients with unresectable progressive or symptomatic desmoid tumors [2]. At a median follow-up of 27 months, patients receiving sorafenib had higher objective responses (33 versus 20 percent) and two-year PFS (81 versus 36 percent) compared with placebo. The most frequently reported adverse events were grade 1 or 2 rash (73 percent), fatigue (67 percent), hypertension (55 percent), and diarrhea (51 percent) [2].

●Pazopanib – In patients with advanced desmoid tumors, pazopanib has demonstrated both improved efficacy and toxicity relative to chemotherapy [30-33]. In an open-label phase II trial (DESMOPAZ), 72 patients with progressive desmoid tumors were randomly assigned to pazopanib at 800 mg daily or to chemotherapy with intravenous methotrexate (30 mg/m²) plus vinblastine (5 mg/m²) given weekly for six months, then every two weeks for another six months [32]. After a median follow-up of approximately 23 months, pazopanib increased the PFS at six months compared with chemotherapy (84 versus 45 percent). Grade ≥3 treatment-related adverse events included hypertension and diarrhea with pazopanib, and neutropenia and transaminitis with chemotherapy. Rates of dose modification due to toxicity were similar in both treatment arms (73 versus 77 percent).

●Sunitinib – Sunitinib, a multitargeted TKI that inhibits the VEGFR tyrosine kinase, is an additional option for patients with moderately symptomatic or progressing tumors [34]. In a phase II study 32 patients with progressive, recurrent, or symptomatic desmoid tumors were randomly assigned to either sunitinib at an oral dose of 52 mg daily or a combination of tamoxifen and meloxicam [34]. In preliminary results, at median follow-up of 27 months, compared with tamoxifen and meloxicam, sunitinib improved objective response rates (75 versus 0 percent) and two-year PFS (81 versus 36 percent). Although toxicities were more frequently reported in those patients receiving sunitinib compared with tamoxifen plus meloxicam, all responded to dose reductions in sunitinib to 37.5 mg.

●Imatinib – Compared with other TKIs, we consider imatinib to be an inferior agent for desmoid tumors because of a lower response rate, but it may have a role if other TKIs have failed or are not tolerated. In 35 evaluable patients who had progressive disease despite local therapy imatinib was associated with an objective response rate of 11 percent and a stable disease rate of 80 percent at three months [35].

Chemotherapy if rapid response needed — We suggest cytotoxic chemotherapy for patients who are severely symptomatic, in particular those patients who have mesenteric involvement, or concerns about absorption. For most patients, we suggest single-agent pegylated liposomal doxorubicin (PLD) rather than a combination approach. Although response rates are higher with doxorubicin-based combination chemotherapy (eg, doxorubicin plus dacarbazine) as compared with anthracycline monotherapy or weekly low-dose methotrexate plus a vinca alkaloid, toxicity is also more significant, and it is not clear that PFS is better. Nirogacestat is a reasonable first-line alternative for selected patients if cytotoxic chemotherapy is not feasible or for patients who prefer to avoid chemotherapy, as long as there are no concerns regarding oral intake. (See 'Nirogacestat (preferred)' above.)

Cytotoxic chemotherapy is associated with response rates ranging from 17 to 100 percent in various studies, with a median of 50 percent [36]. Patients receiving chemotherapy can derive functional and symptomatic benefits, such as a decrease in pain, as early as four weeks into treatment [37,38], and such symptomatic improvement may long precede any decrease in tumor size.

The optimal duration of treatment is not established and is discussed in detail below. (See 'Duration of therapy' below.)

●Anthracycline monotherapy, for most patients requiring chemotherapy (preferred) – There are no direct comparisons of unencapsulated doxorubicin compared with PLD, but we prefer the use of PLD since it has less myelosuppression, febrile neutropenia, alopecia, and cardiotoxicity compared with conventional doxorubicin [39]. We initiate therapy at 40 rather than 50 mg/m² every four weeks. (See "Overview of the initial treatment of metastatic soft tissue sarcoma", section on 'Pegylated liposomal doxorubicin' and "Risk and prevention of anthracycline cardiotoxicity", section on 'Type of anthracycline'.)

Anthracyclines, including doxorubicin [40,41] and PLD [41-45], have been associated with response rates over 75 percent in some series (table 1).

●Combination chemotherapy, if urgent response needed — In well-selected patients with rapidly progressive desmoid tumors for which other local and systemic therapy options have failed, combination chemotherapy can achieve disease control, but with higher rates of toxicity. We reserve combination therapy for patients who need an urgent response to therapy.

●Doxorubicin-containing combinations — Doxorubicin-containing regimens have a higher response rate than non-anthracycline-containing regimens against desmoid tumors, but they are also more toxic [46-53].

In the largest published series, 11 patients received doxorubicin (60 to 90 mg/m²) plus dacarbazine (750 to 1000 mg/m² infused continuously over a 72-hour period) for a median of five cycles [47]. Six of nine evaluable patients had an objective response (two complete, four partial). Cardiac toxicity, myelosuppression, mucositis, and nausea were the most common side effects experienced with this regimen. Results from the largest retrospective studies are outlined in the table (table 2).

●Methotrexate with or without a vinca alkaloid — Several studies have demonstrated the activity of methotrexate plus a vinca alkaloid, with disease control rates (tumor shrinkage or stable disease) that range from 70 to 100 percent (table 3) [38,45,54-61]. Although most studies used the combination of methotrexate and a vinca alkaloid, there is no evidence that combined therapy is better than either methotrexate or a vinca alkaloid alone. In addition, it is unclear if there is a difference between vinorelbine or vinblastine. However, vinorelbine might be preferred given the greater risk of neurotoxicity with vinblastine [61].

Is there a role for hormonal therapy? — The use of hormonal therapy with or without nonsteroidal anti-inflammatory agents (NSAIDs) is controversial. It is unclear if hormonal therapy or NSAIDs have real antitumor activity, given the lack of randomized trial data. Although case reports and series suggest benefit, these must be interpreted with caution given prospective observational data demonstrating spontaneous regression. Nevertheless, given the low risk of harm, hormonal therapy with or without NSAIDs are an option for patients who have slowly progressing tumors after shared decision-making. However, the use of other systemic agents such as nirogacestat and sorafenib are typically preferred [62,63]. (See 'Nirogacestat (preferred)' above.)

In case reports and small series tamoxifen or other selective estrogen receptor modulators such as toremifene, have shown clinical benefit (stable disease and partial or complete responses) [25,36,64-66]. In one of the largest reports, in 20 patients with progressive desmoid tumors, tamoxifen or toremifene was associated with a clinical benefit in 65 percent [67]. This and other studies are summarized in the table (table 4).

Other therapies that have been investigated for hormonal manipulation of desmoid tumors include raloxifene [68], megestrol [69], progesterone [70], goserelin (in combination with tamoxifen) [71], and testolactone (an aromatase inhibitor) (table 4) [72].

Combinations of NSAIDs with hormonal therapy have also been investigated, but it is unclear how much, if any, the individual agents are contributing to the response or if the combination has any synergistic benefit (table 5) [25,72-75]. As an example, in twenty five patients with sporadic and FAP-associated desmoids the, combination of sulindac with either tamoxifen or raloxifene was associated with a response in 24 percent (6 patients) and stable disease in 44 percent (11 patients) [25].

The exact mechanism of action of hormonal agents such as tamoxifen remains largely unknown. Desmoid tumors are known to express estrogen receptors [76], particularly estrogen receptor beta [77], and this may account for the clinical activity of tamoxifen observed in this disease. Alternatively, it has been postulated that the latency of action of hormonal agents and other therapies may be reflective of the deprivation of a growth signal or cytokine [37]. (See "Mechanisms of action of selective estrogen receptor modulators and down-regulators", section on 'Estrogen receptor-beta: A second ER isoform'.)

ALTERNATIVE THERAPIES

Radiation — Radiation therapy (RT) is an appropriate alternative option for patients with moderate to severe symptoms who are not good candidates for surgery or systemic therapy. However, the time to regression after RT alone is often quite long and several years may elapse before regression is complete [78,79].

The recommended dose of RT for definitive therapy is 56 Gy in six weeks at 2 Gy per fraction. Local recurrence rates do not appear to be reduced by the use of higher doses [20].

In a number of reports, RT alone achieves long-term local control in approximately 70 to 80 percent of desmoids [9,10,20,79-88]. The volume of disease does not appear to influence the probability of local control.

Local control rates over 80 percent at three years were noted in a pilot phase II trial employing 56 Gy in 44 patients with inoperable progressive primary, recurrent, or incompletely resected desmoid tumors [79]. Similar findings were also demonstrated in a review that included over 100 patients with desmoid tumors with an overall local control rate for RT alone of 78 percent [9].

Cryoablation — The use of cryoablation is an alternative to surgery and RT for local control of small to moderate sized extra-abdominal desmoids. However, there are limited data comparing cryoablation to other treatment modalities and further work is needed to define the role of cryoablation versus other modalities in the management of desmoid tumors. In a retrospective series of 23 patients receiving cryoablation, 36 percent had a complete response, 28 percent had stable disease, and the remaining 36 percent had a partial response [89]. Two patients developed grade 4 complications (neuropraxia) following treatment, but both resolved several months after the procedure.

TREATMENT OF RECURRENT/RELAPSED DISEASE — 

Multimodality input is important as systemic therapy, surgery, radiation therapy (RT), or local therapies such as cryoablation are all potential treatment options for recurrent disease [5,9,80,90].

●Systemic therapy – Patients who develop a tumor recurrence or disease progression after effective systemic therapy has been discontinued can be retreated with systemic therapy (either the same or an alternative regimen) or evaluated for surgical resection or other local therapies.

Patients with a short progression-free interval (eg, progressive disease within three to six months) or toxicity associated with their previous systemic regimen may be offered an alternative regimen. For instance, if they received nirogacestat, a tyrosine kinase inhibitor such as sorafenib, pazopanib, or sunitinib should be offered. Chemotherapy is an option for tumors that are rapidly enlarging and causing severe symptoms.

Patients with a longer progression-free interval (eg, one year or longer) and minimal toxicity on their prior systemic therapy may be retreated with the same regimen. Retreatment may produce responses that are similar to the original response [54].

●Surgery – If it is feasible and can be carried out using a function-preserving approach, surgical resection is often acceptable for a recurrent extra-abdominal desmoid tumor.

●Avoidance of radiation therapy, in most cases – We avoid RT in most patients with recurrent or relapsed disease due to risk of adverse side effects (eg, tissue fibrosis and radiation-associated cancers) and the availability of other treatment options. However, older adults (age >65 years) may be evaluated for RT if they progress on at least two different systemic therapies, have no other alternative local therapies (such as surgical resection, radiofrequency ablation, or microwave ablation), and are informed of the potential long-term toxicities of RT. (See "Radiation therapy techniques in cancer treatment", section on 'Radiation side effects'.)

MONITORING ON SYSTEMIC THERAPY

Response evaluation during systemic therapy — Desmoid tumors are typically slow growing. Response to systemic therapy can be slow to manifest and may take six months [54,73]. In some situations, the response may be delayed past the point of completion of the treatment regimen [25]. Patients who exhibit a delayed response may even experience an initial increase in tumor size followed by an objective decrease in size [73]. However, if patients continue to have stable disease after six months and a response is needed, alternative therapy should be started. (See 'Duration of therapy' below.)

At many institutions, patients with desmoid tumors who are receiving systemic therapy are imaged every two to three cycles (or every two to three months for continuously dosed agents or weekly treatment regimens). The persistence of disease that is stable or minimally increased in size should not be considered a treatment failure during initial treatment. Symptomatic or functional improvement should be regarded as a reason to continue therapy when changes in the dimensions of the tumor are minimal or absent. From an imaging standpoint, contrast-enhanced magnetic resonance imaging (MRIs) are the preferred approach for following these tumors [91]. A decrease in contrast enhancement over time is an indication of treatment effect [92].

Duration of therapy — For both cytotoxic and noncytotoxic agents, the duration of therapy should be based on toxicity and response. As noted above, responses are typically delayed in desmoid tumors, and this complicates the use of radiographic imaging during therapy to guide the optimal duration of therapy. (See 'Response evaluation during systemic therapy' above.)

There are no data addressing the optimal duration of treatment, and there is no consensus on this issue. Our approach is as follows:

●Although noncytotoxic agents are often continued indefinitely in the absence of toxicity, treatment breaks can be incorporated into the treatment plan, particularly if there are side effects.

●For cytotoxic therapy, dose-limiting toxicities tend to develop over time, and the duration of therapy will depend on the regimen. When using standard anthracyclines (ie, doxorubicin), we typically administer them for up to six cycles. Both pegylated doxorubicin or the weekly methotrexate and vinca alkaloid combinations may be less toxic and are typically administered for up to one year or when reaching a plateau of a smaller tumor. (See 'Chemotherapy if rapid response needed' above.)

POSTTREATMENT SURVEILLANCE — 

For patients who have undergone surgery or completed the planned systemic therapy course, there are no evidence-based protocols for surveillance following treatment. We typically follow patients by clinical examination and radiographic studies (where appropriate) every six months for the first three years, every 12 months to year 6, and then every other year. Consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) [1] suggest a history and physical examination with appropriate imaging every three to six months for two to three years, then annually. However, no surveillance schedule has been proven more helpful than another.

PROGNOSIS — 

Desmoids are characterized by variable clinical behavior. Although most grow progressively larger over time, growth is usually indolent [3,4,23,93-95]. However, some desmoids are locally infiltrative and, rarely, can cause death via destruction of adjacent vital structures and organs. While most centers report a cause-specific mortality rate of 1 percent or less in patients with desmoid tumors at extra-abdominal sites, desmoids are the cause of death in up to 11 percent of patients with familial adenomatous polyposis (FAP) particularly in those with intra-abdominal tumors.

Diagnosis of a desmoid tumor in certain patient populations may impact the behavior of the tumor. Examples include the following:

●Patients with FAP – The desmoids that arise in patients with FAP have a particular predilection for surgical sites (eg, the mesentery or abdominal wall following colectomy, or the site of an ileal pouch-anal anastomosis). With the increasing use of prophylactic colectomy, desmoid tumors have become an important cause of morbidity and mortality.

●Pregnant patients – Pregnancy-associated desmoid fibromatosis is generally associated with good outcomes. Many patients can be monitored during pregnancy.

In patients who have had a resection or local therapy, certain features are associated with a higher risk of recurrence:

●Tumors of the extremity, particularly in distal locations [22,96]

●Size (particularly >7 cm [23,96])

●Sex (females have a higher rate of local recurrence than males)

●Age (younger patients [under age 37 in one series [23] and under age 30 in another series [97] have a higher recurrence rate than older individuals) [8,23,98]

SPECIAL POPULATIONS

Considerations with FAP — The desmoids that arise in patients with familial adenomatous polyposis (FAP) have a particular predilection for surgical sites (eg, the mesentery or abdominal wall following colectomy, or the site of an ileal pouch-anal anastomosis). Prior surgery is a risk factor for the development of desmoids in families with FAP [15,99-105]. In one series, prior abdominal surgery had been performed in 68 percent of patients with FAP and abdominal desmoid tumors; lesions developed within five years after surgery in approximately one-half [103].

Intra-abdominal desmoids that develop in patients with FAP are often unresectable because they diffusely infiltrate the mesentery. Furthermore, recurrences tend to become more frequent and aggressive with each surgical intervention. For these reasons, a multidisciplinary approach that includes systemic therapy is typically required to achieve optimal outcomes for these patients. (See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, and diagnosis", section on 'Familial adenomatous polyposis and Gardner syndrome'.)

Until early elective colectomy became routine in patients with FAP, the dominant cause of death in these patients was carcinoma of the colon at a relatively young age. With the increasing use of prophylactic colectomy, desmoid tumors have become an important cause of morbidity and mortality [100-102,106-108]. Desmoids are the cause of death in up to 11 percent of patients with FAP [107,109]. However, progression is often gradual and approximately 60 percent are still alive 10 years after the diagnosis, some with advanced disease [108,110-112].

Considerations with pregnancy — Pregnancy-associated desmoid fibromatosis is generally associated with good outcomes. In women with a history of a desmoid that developed during pregnancy and was resected, the risk of recurrence is low. In women with an existing desmoid (pregnancy-associated or predating any pregnancy) that is managed with watchful waiting, the risk to the pregnancy is also low. However, there can be some growth during pregnancy and these patients should be managed by a multidisciplinary team.

Observational data suggest good prognosis among those with pregnancy-associated desmoids. In a multi-institutional retrospective series in 92 females with desmoids, 44 (48 percent) had a pregnancy-related desmoid (diagnosed during pregnancy or within six months of delivery) while 48 (52 percent) had a history of desmoid tumor previously diagnosed before conception and either still in situ or completely resected [113]. Initial treatment was resection in 48 percent, medical therapy (cytotoxic chemotherapy with any regimen of agents, antiestrogens or luteinizing hormone-releasing hormone inhibitors, other hormonal therapy, anti-inflammatory drugs, and targeted biologic therapy) in 9 percent, and watchful waiting in 43 percent.

No obstetric complications were directly attributable to the presence of desmoid tumors. Most patients who developed a desmoid during pregnancy were managed with watchful waiting and had some progression of the tumor during pregnancy. Only 4 out of 16 patients required eventual resection. In patients with a history of desmoids prior to pregnancy, 42 percent developed relapse or progression. However, over 90 percent were managed with resection or surveillance. Of note, this review was performed when most patients were managed with surgery versus systemic therapy so the prognosis may be different with current treatment paradigms that favor the use of systemic therapy for many patients.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Soft tissue sarcoma (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Background – Desmoid tumors are slow-growing tumors with no known potential for metastasis or dedifferentiation. However, tumor invasion into vital structures can result in substantial morbidity and may be fatal, especially in the case of intra-abdominal desmoids (eg, familial adenomatous polyposis [FAP]). Desmoid tumors can follow an unpredictable clinical course, with some tumors spontaneously regressing. (See 'Introduction' above.)

●Initial surveillance in asymptomatic or minimally symptomatic patients – For most patients with newly diagnosed desmoid tumors, we suggest active surveillance rather than treatment (Grade 2C); exceptions include patients with moderate or severe symptoms that cannot be controlled with appropriate supportive care (eg, nonsteroidal anti-inflammatory agents [NSAIDs] or acetaminophen); or those in whom progression would cause significant morbidity. Active surveillance typically involves imaging studies at least every three to six months, starting three months after diagnosis. (See 'Asymptomatic or minimally symptomatic patients' above.)

●Management of symptomatic patients – In patients who are symptomatic or develop progression across sequential imaging studies, multidisciplinary input should be obtained. The choice of treatment takes into consideration the location of the tumor, whether it is associated with FAP, potential for adverse effects, and the desired urgency of response. (See 'Approach to management' above.)

•In patients with life-threatening presentations (eg, bowel obstruction), we suggest surgery (Grade 2C). Similarly, for most patients with a sporadic desmoid located in the abdominal wall with disease resectable without undue morbidity, we suggest initial treatment with surgery (Grade 2C). However, if the patient is not a good surgical candidate, radiation therapy (RT) or systemic therapy may be acceptable alternatives, but the time course must be considered. Systemic therapy may afford a response over a period of several weeks to months, while RT may take longer. (See 'Surgery' above.)

•If the patient is symptomatic with a FAP-associated desmoid or a sporadic nonabdominal wall desmoid, but no imminent threat to life or significant morbidity, we suggest systemic therapy (Grade 2C). However, local therapy may be an option in patients who want to avoid the toxicity of systemic agents. (See 'Sporadic nonabdominal wall and FAP associated desmoids' above and 'Alternative therapies' above.)

●Systemic therapy – For initial choice of systemic therapy, we typically suggest nirogacestat (Grade 2C). Tyrosine kinase inhibitors are reasonable alternatives. However, cytotoxic chemotherapy is preferred for patients needing a more rapid response or if there are concerns about absorption of oral medications. (See 'Nirogacestat (preferred)' above and 'Tyrosine kinase inhibitors' above and 'Chemotherapy if rapid response needed' above.)

●Alternative therapies – RT is an appropriate alternative for patients with moderate to severe symptoms who are not good candidates for surgery or systemic therapy. However, the time to regression after RT alone is often quite long and several years may elapse before regression is complete. (See 'Alternative therapies' above.)

●Monitoring on systemic therapy – Response to systemic therapy can be slow to manifest and may take six months. We image every two to three months with contrast-enhanced MRI, but computed tomography is also acceptable. (See 'Monitoring on systemic therapy' above.)

●Posttreatment surveillance – We typically follow patients by clinical examination and radiographic studies (where appropriate) every six months for the first three years, every 12 months to year 6, and then every other year. (See 'Posttreatment surveillance' above.)