Active Surveillance in Patients with Extra-abdominal Desmoid-Type Fibromatosis: A Pooled Analysis of Three Prospective Observational Studies

Purpose: Three prospective observational studies (Italy, the Netherlands, and France) on active surveillance (AS) in patients with extra-abdominal desmoid-type fibromatosis support AS as a first-line approach. Identifying prognostic factors for the failure of AS will help determine the strategy. The aim of this study was to investigate the prognostic impact of clinical and molecular variables in a larger series. Experimental Design: Data available as of January 31, 2024, from the three studies, in which patients were followed for ≥3 years, were pooled. Patients ≥18 years of age, with primary sporadic desmoid-type fibromatosis, and with CTNNB1 mutations available were eligible. The primary study endpoint was treatment-free survival (TFS). Secondary endpoints included the incidence of RECIST progression, spontaneous RECIST regression, and regression post-RECIST progression. Results: Patients (n = 282) with a median follow-up of 53 months (IQR, 39–63) were included. The 3- and 5-year TFS rates were 67% and 66%, respectively; the 3- and 5-year crude cumulative incidences were 33% and 34% for RECIST progression, 26% and 34% for RECIST regression, and 33% and 38% for regression post-RECIST progression, respectively. In multivariable analysis, larger tumor size, mutation type, and tumor locations were associated with lower TFS. The specific mutation (S45F), larger tumor size, and extremity and trunk locations were all associated with a lower probability of spontaneous RECIST regression. Conclusions: This study confirms that spontaneous regression occurs in a significant proportion of patients and that two-thirds are treatment free at 5 years. Initial tumor size, CTNNB1 mutation, and location should be factored into the initial decision-making process.