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  • Despite the introduction of a preventive human papillomavirus vaccine, both the incidence of anal cancer and the anal cancer–specific mortality rate continue to rise in the United States.

  • Concurrent chemoradiation remains the standard of care for curative-intent therapy for patients with newly diagnosed, locoregional anal cancer.

  • To date, there are no data to support benefit with chemotherapy before or after chemoradiation for patients with locoregional anal cancer.

  • Salvage surgery with abdominoperineal resection remains the standard of care for patients with nonmetastatic, locoregional anal cancer that recurs after chemoradiation.

  • Combination chemotherapy is the current treatment recommendation in the frontline setting for patients with inoperable, metastatic anal cancer.

  • Immune checkpoint blockade therapies, either as monotherapy or as a clinical trial option, should be considered for patients with treatment-refractory anal cancer.


Carcinoma of the anal canal is extremely rare, representing approximately 2% to 3% of all gastrointestinal (GI) malignancies. It was estimated that in 2020, 8590 patients (5900 female) would be diagnosed with carcinoma of the anal canal in the United States, resulting in 1350 deaths.1 The incidence of this disease continues to rise steadily. Over the past 20 years, increasing rates of advanced (metastatic) stage at initial presentation have been reported in the United States and are linked to a rise in cancer-specific mortality rates.2 Still, a practicing oncologist will evaluate and treat less than one such patient per year. The majority of anal cancer is squamous cell carcinoma (SCC) and typically arises within the anal mucosa.3 Traditionally, more than 70% of locoregional anal canal caners are cured with the combined modalities of chemoradiation,4 reserving an abdominoperineal resection (APR) for salvage therapy of patients with persistent or recurrent disease.5 This chapter focuses on the multimodality treatment of SCC of the anus (SCCA) and the emerging role of immunotherapy in management of patients with this disease.


Optimal treatment of patients with SCCA requires sound understanding of the anatomy of the anus, which includes the anal canal, anal verge (AV), and anal margin (AM). The anal canal is variable in length and is 2 to 3 cm long in women and 3 to 5 cm in men. The AV is the visible portion of the anus seen with gentle traction applied to the buttocks, and the AM is a region that extends 5 cm radially from the AV around the anal skin (Fig. 33–1). Nomenclature is vital, and accurate description of the tumor location is critical for optimal management. Although classification of these tumors by their histologic definition may offer a more consistent approach to guide diagnosis and treatment,3 meaningful data suggest such a singular approach to all SCCA may be inadequate, and a tailored approach to these cancers may be more important. For example, malignancies of the AM that do not involve the anal sphincter complex and are smaller than 2 cm ...

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