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Carcinoma of the anal canal is a rarely discussed malignancy representing 1.9 % of all identified gastrointestinal malignancies (1). It is estimated in the year 2009 that approximately 5290 patients will be diagnosed with carcinoma of the anal canal, resulting in 710 deaths (1). A practicing oncologist will evaluate and treat less than one such patient per year. The majority of anal carcinoma arises within the mucosa of the anus and are of squamous cell histology (2). Traditionally, 74 to 90% of carcinomas of the anal canal are cured with the combined modalities of chemoradiation, reserving an abdominoperineal resection (APR) for salvage therapy (3). As a consequence of its exceptional response to multimodality treatment and its infrequent presentation, few clinical studies on carcinoma of the anal canal have been completed. Furthermore, the majority of studies that have been recently completed are often small single-institution studies. Little has changed over the past three decades, resulting in minimal modifications in the treatment approach. Hence, the ability to redefine the standard of care of these patients exists. This chapter focuses primarily on the historical and current treatment of squamous cell carcinoma of the anal canal and the potential innovative strategies that lie ahead.

A recent population-based analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data between the years 1973 and 2000 reported a steady overall increase of anal canal cancers in the United States with this increase more pronounced for men (4). Whereas men previously had lower incidence rates than women, that gender difference in the annual incidence has normalized with similar rates demonstrated at 2.04 per 100,000 for men and 2.06 per 100,000 for women. There has been an overall increase in the rate of in situ disease from 0.09 to 0.45 per 100,000 persons, surpassing a less pronounced increase in rate of invasive disease, with a more advanced disease stage inversely associated with overall survival. Disparities exist, in particular for black men who exhibited a 2.5-fold increase in incidence rate from 1994 to 2000 and with black patients overall having a consistently higher mortality with a poorer stage-specific relative survival at 5 years when compared with white patients. An especially high incidence of anal cancer has also been seen in the populations of men who have sex with men (MSM) and patients infected with human immunodeficiency virus (HIV) (5).

The anal canal is approximately 4 cm wide and is composed of the region extending from the proximal anorectal ring to the distal anal verge (margin) (Fig. 22-1). It is imperative to differentiate the borders of the rectum, anal canal, and margin. As various definitions of the normal anal canal anatomy exist, classifying these tumors by a histologic definition based on the lining mucosa offers a more consistent approach to guide diagnosis and treatment (2). The majority of anal carcinomas are of squamous ...

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