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Anal squamous cell carcinoma (SCAC) is a human papillomavirus (HPV) driven malignancy. Given inadequate HPV-vaccination rates, SCAC will continue to be a public health concern. SCAC is commonly diagnosed in the local or locoregional setting in which definitive chemoradiation provides the opportunity for cure and has high control rates. A minority of patients will develop recurrence or present with metastatic SCAC. Given the rarity of this disease, research has lagged compared to many other solid tumors. Historically, treatment has been based on extrapolating management approaches from more common squamous cell carcinoma malignancies and/or small case series or case reports. Fortunately, dedicated prospective clinical trial investigation in the advanced setting has emerged in recent years. Here, we review the current strategies for treatment along with remaining challenges and viable next steps for the management of metastatic SCAC.

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches