Anal Cancer

Abstract The major objectives of treatment of cancers that arise in the anal canal and perianal skin are cure and preservation of anal function. The prognosis for both survival and function deteriorates as the primary tumor enlarges, and the probability of cure diminishes as cancer metastasizes to the regional lymph nodes and to extrapelvic sites. Although the incidence of anal cancer has been increasing in many countries over the past 30 years, the relative rarity of such cancers (incidence about 0.5 to 1 per 100,000) has meant that there have been few large groups of patients in whom prognostic factors have been assessed by multivariate analysis or similar statistical techniques. In the 1987 and 1997 editions of the TNM classification, the anal canal is defined as that part of the intestine that extends from the rectum to the perianal skin (to the junction with the hair‐bearing skin). The extent of the perianal area is not defined in the manual, but, by common usage, is considered the skin within a 5‐cm radius of the anal verge. Prior to the 1987 classification, several different conventions were used to describe the anatomy of the anal region, so that comparisons of different series are often not possible. A significant change in the categorization system for primary anal canal cancers was also made in 1987, by basing classification on the measured size of the tumor. The T‐category is determined by the largest diameter of the primary carcinoma, measured in centimeters (T1–T3‐categories), except when there is direct invasion of adjacent major organs (T4‐category). Formerly, it was necessary to estimate clinically the proportion of the length or circumference of the canal involved, and whether the external sphincter was infiltrated. Perianal cancers continued to be categorized by measured size as previously. The histological classification of malignancies of the anal canal and of the perianal skin has not changed substantially over the past 30 years. The 1989 edition of the World Health Organization (WHO) Classification System described three major subtypes of squamous‐cell cancer of the anal canal, namely large‐cell keratinizing, large‐cell nonkeratinizing (transitional), and basaloid. The view that all are variants of squamous‐cell cancer was supported by an analysis of keratin profiles. Many clinical investigators, agreeing that the prognostic value of histological subtyping is marginal, group all three subtypes as squamous‐cell or epidermoid carcinomas of the anal canal. The shift in treatment of anal canal cancer from radical surgery to primary radiation therapy, commonly combined with cytotoxic chemotherapy, allows preservation of function in many patients, and has affected assessment of prognostic features. Detailed gross and histopathological assessment of excised tissues, which formed the cornerstone of many earlier analyses, is no longer possible. It has not yet been established that all features of prognostic value in patients treated surgically are equally predictive of outcome following radiation with/without chemotherapy. In the discussion that follows, cancers of the anal canal and of the perianal skin are considered separately. All comments address the patient newly diagnosed and undergoing initial treatment, except where indicated.