Mohs surgery reduces recurrence for dermatofibrosarcoma protuberans: A multicentre cohort study

Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer with an annual incidence of 0.8 to 4.5 cases per million.1 Metastasis and death from DFSPs are rare, while local recurrence has been reported in up to 21% of cases.2 Systematic reviews and comparative studies suggest Mohs micrographic surgery (MMS) improves outcomes and reduces recurrence compared to wide local excision (WLE), but most data come from small single-centre studies.3-7 The few multicentre studies have not employed multivariable modelling to compare MMS to WLE and lack long-term outcomes.8-10 This multicentre cohort evaluates characteristics of DFSP associated with positive margins and long-term outcomes by surgical approach. This retrospective study included biopsy-proven DFSPs treated at Mass General Brigham, Cleveland Clinic and Yale-New Haven Hospital from January 2008 to March 2025. Data included demographics, tumour characteristics (location, diameter, depth of invasion, and pathologic features), surgical approach, post-resection margin status, and recurrence. Recurrence (local, in transit, nodal, or distant) was ascertained through pathology reports and documentation by a board-certified dermatologist. Patients who did not develop recurrence were censored at last dermatologic follow-up. Chi-squared and Mann–Whitney U tests were used to compare characteristics between tumours with negative and positive margins. Univariate logistic regression was performed to assess associations between individual factors and margin status. Variables with a p-value < 0.2 were included in the multivariable regression model. Cox proportional hazards modelling was used to evaluate recurrence-free survival stratified by surgical approach (MMS vs. WLE), adjusting for significant factors. Log-rank and life table analyses were used to compare survival functions between both groups. Statistical analyses were conducted using Python v3.10. Two hundred and five patients were included with a mean age of 42.8 years (SD = 15.9) and follow up of 4.41 years (SD = 3.6). 82 (40%) were male, 151 (73.7%) were White, and 8 (3.9%) were immunosuppressed. Ninety-eight tumours (47.8%) had diameter ≥ 3 cm, 79 (38.5%) had invasion of fascia, muscle or periosteum, and 28 (13.7%) were located on the head and neck. Ninety-nine (48.3%) were treated with WLE and 105 (51.2%) with MMS. Overall, 46 (22.4%) had positive margins and 9 (8.4%) had recurrence. There was an increased incidence of positive margins for tumours located on the head and neck versus trunk and extremities (50.0% vs. 17.7%; p < 0.001), with deep invasion (30.3% vs. 15.1%; p = 0.01), and treated with WLE versus MMS (37.4% vs. 8.6%; p < 0.001). Age, sex, immunosuppression, tumour diameter, perineural invasion, lymphovascular invasion and fibrosarcomatous change were not associated with positive margins. Multivariable regression confirmed WLE as a significant predictor for positive margins compared to MMS (OR 5.99, p < 0.001) (Table 1). Additional predictors included head and neck location (OR 3.98, p = 0.003) and deep invasion beyond subcutaneous fat (OR 2.45, p = 0.022). Cumulative recurrence at 5 years was 2.1% with MMS and 11.9% with WLE. Cox proportional hazards demonstrated a significant difference in DFSP-free survival between MMS and WLE when adjusting for other predictors of margin status (Figure 1; log-rank p = 0.033). Tumours with deeper invasion, treated with WLE, or located on the head and neck were more likely to have positive margins, highlighting challenges of complete resection in anatomically complex areas. Cumulative recurrence was six-fold lower with MMS, which highlights the importance of initial margin control. While MMS was associated with decreased recurrence, WLE remains an acceptable treatment option when MMS is not available. Outcomes with WLE may be optimized utilizing other types of complete margin assessment, such as en face processing, although this study did not evaluate non-MMS complete margin assessment. While this study is limited by its retrospective design and potential selection bias in surgical approach, MMS remained associated with decreased recurrence when controlling for other factors associated with incomplete excision. None. SRC: Sol-Gel Technologies (investigator), Castle Biosciences (consultant), Regeneron (consultant). ATV: Castle Biosciences (investigator), Sol-Gel Technologies (investigator), Inhibitor Therapeutics (advisory board). ESR: Regeneron (consultant), Checkpoint Therapeutic (consultant), Feldan Pharmaceuticals (consultant), Regeneron (investigator), Merck (investigator), Castle Biosciences (investigator), Skin Cancer Outcomes Consortium (executive officer), Skin Cancer Champions (founder). NAR: Chronicle Medical Software (consultant) and Regeneron (consultant). BK, CEP, EEK, JXW, KJK, TJO, AKA: No disclosures. Reviewed and approved by the Mass General Brigham Human Research Office, the Cleveland Clinic Institutional Review Board, and the Yale Institutional Review Board. Not applicable. The data that support the findings of this study are available from the corresponding author upon reasonable request.