Outcomes for patients with cutaneous squamous cell carcinoma (CSCC) treated with Mohs micrographic surgery (MS) in the United States have never been prospectively defined. Risk factors as they relate to outcomes are primarily derived from single-institution, retrospective data without regard for treatment modality. The American Joint Committee on Cancer Staging Manual, Eighth Edition, and the Brigham and Women's Hospital T staging systems have not been prospectively validated.

To prospectively quantify outcomes by T stage and verify historically high-risk features as they pertain to outcomes in MS-treated CSCC.

A 5-year, prospective, multicenter analysis of patients undergoing MS for invasive CSCC was conducted.

The study enrolled 647 patients with 745 tumors. The 5-year local recurrence (LR)-free survival, nodal metastasis (NM)-free survival, and disease-specific survival were 99.3%, 99.2%, and 99.4%, respectively. Both staging systems were predictive of NM, disease-specific death, and all-cause death; neither was predictive of LR. Although Breslow depth was statistically associated with LR, NM, and disease-specific death, incidental perineural invasion was not.

The Brigham and Women's Hospital and the American Joint Committee on Cancer Staging Manual, Eighth Edition T staging systems were published after study enrollment, therefore T stages were retrospectively applied using the prospectively collected data.

MS is a highly effective treatment for CSCC and may mitigate factors typically considered high risk. Uniform reporting of Breslow depth should be considered in CSCC. The American Joint Committee on Cancer Staging Manual, Eighth Edition, and the Brigham and Women's Hospital staging system are useful prognosticators but are not predictive of LR after MS.