Mohs Surgery vs Wide Local Excision in Primary High-Stage Cutaneous Squamous Cell Carcinoma
Authors: David M. Wang, Michelangelo Vestita, Fadi G. Murad, Frederick C. Morgan, Rachael Rowley, Eleni M. Rettig, William Lotter, Abigail B. Waldman, Emily S. Ruiz, Chrysalyne D. Schmults
Journal: JAMA Dermatology (2025)

Importance High-stage cutaneous squamous cell carcinoma (cSCC) has an increased risk of recurrence, metastasis, and mortality. Studies investigating the outcomes of high-stage cSCC among patients treated with Mohs surgery compared with those treated with wide local excision (WLE) are limited. Objective To assess the outcomes of primary high-stage cSCC among patients treated with Mohs surgery compared with those treated with WLE. Design, Setting, and Participants This retrospective cohort study using propensity score weighting was conducted in a tertiary academic medical center in Boston, Massachusetts. Patients were included if they had primary high-stage cSCC and had been treated with either Mohs surgery or WLE between January 1, 2000, and December 31, 2019. Data analysis was performed between November 3 and 6, 2023. Exposures Primary surgical treatment with Mohs surgery or WLE. Main Outcomes and Measures Outcomes included local recurrence, nodal metastasis, distant metastasis, any recurrence (ie, a composite outcome of recurrence or metastasis), and disease-specific death. Propensity scores were estimated via logistic regression using baseline patient and tumor characteristics. Competing risk regression analysis was used to compute crude and inverse probability of treatment weighting (IPTW), cause-specific hazard ratios (HRs), and Fine-Gray subdistribution HRs and to derive cumulative incidence functions stratified by Mohs and WLE. Results This study included 216 patients with high-stage cSCC who had a mean (SD) age of 73.5 (13.3) years; 151 (69.9%) were men and 65 (30.1%) were women. The median follow-up time was 33.1 months (IQR, 11.3-77.6 months). After IPTW, the baseline characteristics were well balanced between the WLE and Mohs surgery treatment groups, with absolute standardized differences of less than 0.10 across all characteristics. In the IPTW competing risks model, the 3-year cumulative incidence of all adverse outcomes were greater among patients in the WLE group compared with those in the Mohs surgery group, including local recurrence (19.8% vs 9.6%; weighted cause-specific HR, 2.33 [95% CI, 1.39-3.92]; P = .001), nodal metastasis (17.9% vs 11.0%; weighted cause-specific HR, 1.80 [95% CI, 1.07-3.02]; P = .03), distant metastasis (8.4% vs 4.4%; weighted cause-specific HR, 2.10 [95% CI, 0.97-4.57]; P = .06), any recurrence (32.0% vs 15.8%; weighted cause-specific HR, 2.38 [95% CI, 1.57-3.61]; P &amp;amp;lt; .001), and disease-specific death (17.5% vs 7.1%; weighted cause-specific HR, 2.74 [95% CI, 1.54-4.88]; P = .001). Conclusions and Relevance The findings of this cohort study suggest that Mohs surgery was associated with improved outcomes in the treatment of primary high-stage cSCC compared with WLE. These findings further suggest that Mohs surgery or alternative methods of peripheral and deep en face margin assessment should be offered as first-line treatment.