Anal Carcinoma

Introduction

Anal cancer is relatively rare, accounting for only 1.5% of gastrointestinal malignancies. However, its incidence is on the rise. Although chemotherapy/radiotherapy is the primary mode of treatment of anal squamous cell cancer (SCC), abdominoperineal resection is still required at times. The cornerstones of successful therapy are timely diagnosis, accurate staging, and routine surveillance. Although major advances have been made in the treatment of anal cancer, many challenges still exist, especially in patients who have recurrent or metastatic disease and are immunocompromised. In this chapter we offer a management scheme for both anal canal and perianal SCC.

Anatomic Considerations

The anal region is composed of the anal canal and the perianal skin. The “surgical” or “functional” anal canal extends from the anal verge to the anorectal ring. The perianal skin extends an additional 5 cm from the anal verge. The latest version of the American Joint Committee on Cancer Staging manual suggests a classification of anal cancers based on where they are located. The system divides the region into three easily identifiable regions: anal canal, perianal region, and skin. Anal canal lesions are lesions that cannot be visualized at all or are incompletely visualized with gentle traction placed on the buttocks. In contrast, perianal lesions are completely visible and fall within a 5-cm radius of the anal opening. Finally, skin lesions fall outside the 5-cm radius of the anal opening. The strength of this classification system is that it allows all clinicians, including gastroenterologists, surgeons, advanced practice providers, and medical and radiation oncologists, to perform this simple examination in the office without the need for an anoscope or a clear understanding of the anatomic landmarks of the region. Accurate classification of anal cancers is important because true anal canal lesions may have a more aggressive biology requiring chemotherapy/radiotherapy, whereas lesions of the perianal skin may be treated simply with local excision.

The arterial supply of the anus is derived from branches of the superior rectal artery, the inferior rectal branch of the pudendal artery, and branches of the median sacral artery. The venous drainage of the anal canal has two patterns. Above the dentate line, the venous blood drains through the terminal branches of the superior rectal vein into the inferior mesenteric vein and portal system, and below the dentate line it drains via the inferior rectal vein into the pudendal vein, which itself drains into the internal iliac vein. Lymphatic drainage of anal cancers is dependent upon the location of the lesion with respect to the dentate line. Cancers arising proximal to the dentate line drain to perirectal and paravertebral lymph nodes in tandem with rectal carcinomas, whereas cancers distal to the dentate line drain to inguinal and femoral nodes.

Epidemiology

Multiple studies have shown that the incidence of anal carcinoma is increasing. In the United States between 1973 and 1979, the incidence per 100,000 was 1.06 in men and 1.39 in women. From 1994 to 2000 this incidence almost doubled, with a rate of 2.04 per 100,000 in males and 2.06 per 100,000 in females. Similarly, in 2011 there were an estimated 6230 new cases and 780 related deaths, whereas in 2008, the number was 5000 new cases and 680 related deaths, demonstrating a significant increasing trend from 2003 when approximately 4000 new cases and 500 related deaths were recorded. In Denmark, similar trends were documented, and age-adjusted incidence rates per 100,000 person-years showed an increase from around 0.2 among both men and women to 0.5 among men and 1.0 among women during the period 1943-1997. A peak in incidence is noted in the seventh decade, with women more commonly affected than men. Risk factors for developing anal cancer include human immunodeficiency virus (HIV) seropositivity, low CD4 count, persistent infection with high-risk human papillomavirus genotypes (16, 18, 31, 33, and 35), infection with multiple genotypes, cigarette smoking, anal receptive intercourse, immunosuppression, and female gender.