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, France) on active surveillance (AS) in patients with extra-abdominal desmoid-type fibromatosis (DTF) support AS as a frontline 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 31st, 2024, from the three studies, in which patients were followed for ≥3 years, were pooled. Patients ≥18 years old, with primary sporadic DTF 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: Two hundred and eighty-two patients (n = 282) with a median follow-up of 53 months (IQR, 39-63) were included. Three-year and five-year TFS were 67% and 66%, crude cumulative incidences (CCI) of RECIST progression were 33% and 34%, of RECIST regression 26% and 34% and of regression post-RECIST progression 33% and 38%. In multivariable analysis, larger tumour size, mutation type, tumor locations were associated to lower TFS. The specific mutation (S45F), larger tumor size, and extremity and trunk location 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.