Mohs micrographic surgery may be associated with improved outcomes compared with wide local excision in the treatment of primary high-stage cutaneous squamous cell carcinoma, according to a retrospective cohort study conducted at a tertiary academic medical center.

In the study, published in JAMA Dermatology, researchers analyzed 216 patients over a 20-year period, finding that Mohs surgery resulted in significantly lower rates of recurrence, metastasis, and disease-specific mortality.

After inverse probability of treatment weighting, the 3-year cumulative incidence of local recurrence was 9.6% in the Mohs surgery group compared with 19.8% in the wide local excision (WLE) group (weighted cause-specific hazard ratio [HR] = 2.33, 95% confidence interval [CI] = 1.39–3.92, P = .001). The incidence of nodal metastasis was 11.0% for Mohs surgery vs 17.9% for WLE (HR = 1.80, 95% CI = 1.07–3.02, P = .03), while distant metastasis rates were 4.4% and 8.4%, respectively (HR = 2.10, 95% CI = 0.97–4.57, P = .06). A composite outcome of any recurrence was observed in 15.8% of Mohs surgery–treated patients vs 32.0% of WLE-treated patients (HR = 2.38, 95% CI = 1.57–3.61, P < .001). Disease-specific mortality occurred in 7.1% of Mohs surgery–treated patients compared with 17.5% of those treated with WLE (HR = 2.74, 95% CI = 1.54–4.88, P = .001).

The study cohort had a mean age of 73.5 years (standard deviation = 13.3), with 69.9% of participants being male. The median follow-up time was 33.1 months (interquartile range = 11.3–77.6). Propensity scores were estimated via logistic regression to balance baseline characteristics, and competing risk regression models were used to derive cumulative incidence functions.

"These findings suggest that patients with primary high-stage [cutaneous squamous cell carcinoma] (cSCC) should be offered first-line treatment with Mohs surgery or alternative methods of peripheral and deep en face margin assessment whenever possible," said lead study author David M. Wang, MD, of the Department of Dermatology at Brigham and Women’s Hospital, and his colleagues.

Mohs surgery, which utilizes frozen section analysis for complete margin assessment, showed superior outcomes compared with WLE, which relies on the bread-loafing technique that samples only a portion of excised margins. The researchers noted that incomplete tumor removal as a result of sampling error in WLE could contribute to the observed differences in recurrence and metastasis rates.

Existing National Comprehensive Cancer Network guidelines recommend Mohs surgery or alternative en face margin assessment techniques for cSCC tumors with high-risk features such as poor differentiation, perineural invasion, or invasion beyond subcutaneous fat.

The researchers acknowledged study limitations, including the retrospective design and single-center data set, which may affect generalizability. However, recurrence and metastasis rates observed in this study aligned with prior literature on high-stage cSCC outcomes. Further research is needed to assess the role of adjuvant therapies, including radiation, in combination with Mohs surgery for high-stage cSCC, particularly in reducing local and locoregional recurrence.

Full disclosures are detailed in the study.