Anal Carcinoma


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.


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.

Squamous Cell Carcinoma of the Anal Canal

Squamous cell carcinoma of the anal canal is five times more common than perianal SCC. Epidermoid cancers collectively include all variants of SCC (cloacogenic cancer)—keratinizing, nonkeratinizing, and basaloid. For the most part, no distinction needs to be made between the subtypes of epidermoid cancer when considering treatment. Symptoms include anal bleeding, discharge, a palpable lump, or discomfort upon defecation, but these symptoms are common and nonspecific. Patients are frequently misdiagnosed with a benign condition such as hemorrhoids or an anal fissure prior to the diagnosis of anal cancer. Because diagnosis is often delayed, epidermoid cancers are found to have infiltrated the sphincter muscles or beyond in up to 90% of patients, and lymph node metastases are present in one third of patients. Evaluation should include a complete anorectal examination with external inspection of the anoderm, digital examination, anoscopy, proctoscopy, and examination of inguinal nodes. Careful notation should be made of the size, location, and mobility of the mass and associated perirectal and inguinal lymphadenopathy, and in women, a pelvic examination should be performed to look for any associated lesions or invasion of tumor into the vagina. A complete examination and biopsy may require use of an anesthetic for patients with significant pain but often can be completed in the office setting. HIV testing should be considered, along with a CD4 count, if indicated.

Staging is completed once diagnosis is confirmed by biopsy. According to the seventh edition of the cancer staging manual of the American Joint Committee on Cancer, a TNM system is utilized. T level is determined by tumor size in the greatest dimension, as follows: T1 lesions are less than 2 cm, T2 tumors are more than 2 cm but no more than 5 cm, T3 tumors are more than 5 cm, and T4 tumors are those of any size that invade adjacent organ(s)—for example, the vagina, urethra, and bladder. It is important to note that direct invasion of the rectal wall, perirectal skin, subcutaneous tissue, or sphincter muscle is not classified as T4 disease.

Nodal level is based on location of positive nodes, as follows: N0, no regional lymph node metastasis; N1, metastasis in perirectal lymph nodes; N2, metastasis in unilateral internal iliac and/or inguinal lymph nodes; and N3, metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes. The most current version of the National Comprehensive Cancer Network Guidelines (version 2.2014) suggests that all patients who are found to have anal cancer should undergo a computed tomography (CT) scan of the chest, abdomen, and pelvis or pelvic magnetic resonance imaging (MRI). Further staging workup is dictated by T level and physical examination findings of suspicious lymph nodes. A positron emission tomography (PET) scan is reserved for persons with T2-T4 or N + disease, and biopsy or fine-needle aspiration is suggested in persons with suspicious nodes. However, in our practice, all newly diagnosed patients with anal cancer undergo CT of the chest, abdomen, and pelvis, as well as pelvic MRI. We routinely request a PET scan for all patients regardless of clinical T and N stages. In most cases we forgo biopsy or fine-needle aspiration of suspicious nodes and consider positive PET avidity to indicate nodal metastasis.

The goals of therapy in patients with SCCs of the anal canal are to ablate the neoplasm and preserve anal sphincter function. Originally, treatment of anal canal SCC was surgical, with abdominoperineal resection (APR) the standard of care. However, local recurrence rates were high, 5-year survival was only 40% to 70%, and the morbidity with a permanent colostomy was considerable. In 1974, Nigro and coworkers first described treatment with radiation and concurrent 5-fluorouracil (5-FU) and mitomycin C (MTC). This combination revolutionized the treatment of anal canal SCC. Chemotherapy/radiotherapy alone results in a complete response in 70% (64% to 86%) of patients and an overall survival rate at 5 years of 75% (66% to 92%). Two randomized trials, one conducted in the United Kingdom and the other in Europe, have confirmed the superiority of combined modality treatment over radiation alone. Nigro and colleagues described using 30-Gy external beam radiation with 5-FU and MTC and demonstrated a complete pathologic response in 21 of 26 patients treated (81%). Since that time, various radiation doses (30 to 60 Gy) and chemotherapeutic regimens have been used with similar complete pathologic responses (45% to 100%) and survival rates (70% to 90%). As a result, surgery for anal canal SCC has been reserved for patients with persistent or recurrent disease after chemotherapy/radiotherapy. We treat all newly diagnosed epidermoid anal canal cancers with chemotherapy/radiotherapy regardless of stage. In patients with frank incontinence or a malignant fistula, it is our practice to first perform laparoscopic fecal diversion before chemotherapy/radiation is used. The results of the treatment are then assessed and consideration is given to APR for persistent disease.

Patients are re-evaluated 8 to 12 weeks after completion of chemotherapy and radiation treatments and classified according to whether they have a complete remission, persistent disease, or progressive disease. The primary cancer will generally regress by about 6 to 12 weeks after the completion of treatment but sometimes may take longer. A pale, irregular scar is usually visible at the site of the primary tumor. The base and edges of this fibrotic scar have a rubbery texture, whereas any hard, tender, or ulcerated area is suspicious for residual cancer. Patients can be classified as having a complete remission without biopsy verification if they have no clinical evidence of disease. However, a clinical assessment of progressive disease requires a biopsy. When residual or recurrent cancer is identified, further radiation and chemotherapy occasionally may be effective, provided the initial radiation dose had not been to the limit of normal tissue tolerance. However, APR is often necessary.

A salvage APR is required in approximately 30% of cases as a result of either primary nonresponse or recurrence. In the majority of such cases, long-term survival can be achieved after salvage surgical operations. Prognosis is worse in persons who initially presented with lymph node metastasis or who received a radiation dose of less than 55 Gy during initial combined chemotherapy/radiation therapy. Another important prognostic factor of survival after resection is the margin status. For patients in whom a negative margin can be achieved, the 5-year overall survival rate approaches 75%. Other predictors of a poor outcome after salvage surgery include tumor size greater than 5 cm, adjacent organ involvement, male gender, and associated comorbidities. Salvage surgery is also reported to be associated with substantial morbidity in up to 72% of patients, including delayed perineal wound healing, pelvic abscess, perineal wound hernia, urinary retention, and impotence. A treatment algorithm for anal canal cancer is outlined in Fig. 15-1 .

Jul 15, 2019 | Posted by in GENERAL | Comments Off on Anal Carcinoma

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