The Management of Advanced Anal Squamous Cell Carcinoma
Abstract
Cancers of the anal canal are rare malignancies defined anatomically from the anorectal junction to the perianal region. The most common histotype is anal squamous cell carcinoma (ASCC), which represents 1%–2% of all gastrointestinal cancers. Despite recent advances in the treatment of modifiable risk factors, the incidence of ASCC continues on a slow but unabated upward trajectory driven by predisposing factors including smoking, human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections, and immunosuppression, amongst others. Metastatic ASCC (mASCC), either de novo stage IV disease or distant recurrence following definitive concurrent chemoradiation, is also increasing in frequency, representing 10%-30% of all diagnoses. While localized disease is curable with chemoradiation, using mitomycin-c and fluoropyrimidine-based sensitizing chemotherapy, advanced or metastatic disease is associated with significantly worse outcomes and a historical median overall survival (OS) below 20 months and 5-year OS between 19%–30%. The management of advanced or metastatic ASCC has undergone significant changes in the past decade, and herein we will highlight the current treatment paradigm and future directions in this field.
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