Anal or Anal Canal Cancer
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|ANAL CANAL CARCINOMA
Epidemiology, etiology, and Risk Factors
In the United States, anal canal carcinoma occurs more frequently in women than men. More than 80% of anal canal tumors occur in individuals > 60 years of age. Recent epidemiologic studies suggest that receptive anal intercourse is strongly related to anal cancer. The incidence rate of anal cancer for single men is reported to be six times that for married men; in people < 35 years old, anal carcinoma is more common in men than women. A history of genital warts has been observed, suggesting that papillomavirus may be an etiologic factor.
Signs and Symptoms
The diagnosis of anal canal carcinoma is usually delayed because the symptoms (bleeding, pain, and sensation of mass) are so often attributed to benign anorectal disorders, such as hemorrhoids or anal fissures.
Evaluation should include a careful rectal examination, endoscopic examination with description of lesion size, and assessment of whether there is invasion into adjacent organs (vagina, urethra, or bladder). Reexamination under general anesthesia may be necessary. A diagnostic incisional biopsy is required. Pelvic CT is suggested to evaluate pelvic nodes. Although distant metastases are uncommon at diagnosis, a chest x-ray and liver function tests are recommended. Suspicious inguinal nodes discovered on physical examination must be assessed pathologically. The incidence of inguinal nodal metastases at diagnosis varies from 13% to 25%. The presence of perirectal, inguinal, and pelvic lymph node involvement correlates with tumor size and isunusual for tumors < 2 cm in diameter. Formal groin dissection is notadvised; needle aspiration should be performed with limited surgical biopsy if results of aspiration are inconclusive.
Squamous cell carcinomas Most anal canal malignancies are squamous cell carcinomas. These have been cllassified as cloacogenic carcinomas, basaloid carcinomas, transitional cell carcinomas, or mucoepidermoid carcinomas. However, there is little difference in the natural history of these various types.
Unusual tumors arising in the anal canal include small-cell carcinomas, anal melanomas, and lymphomas. Small-cell carcinomas of the anal canal are aggressive neoplasms similar in natural history to bronchogenic small-cell carcinomas. If such a histology is identified, the clinician should be alerted to the possibility of early distant metastases, and treatment should include chemotherapeutic regimens used in bronchogenic small-cell carcinomas.
Surgery In selected individuals with small superficial tumors, local excision has achieved adequate local control and survival. However, most studies of local excision have been retrospective, with small numbers of patients. Prior to the advent of primary radiotherapy and combined-modality treatment (see below), abdominoperineal resection was considered the conventional treatment for patients with invasive anal canal cancer. Unfortunately, even with radical surgical procedures, local recurrences are frequent.
Radiation therapy Trials of primary external-beam radiotherapy in the treatment of anal canal carcinomas have used doses varying between 4,500 and 7,550 cGy. Local control rates of 60%-90%, with 5-year survival rates of 32%-90%, are similar to those of surgical series when the trials are controlled for tumor size. Interstitial radiation therapy alone has been used primarily in Europe for early-stage lesions. A relatively high radiation dose is delivered to a small volume. This modality carries a high potential for radiation necrosis and fails to incorporate treatment of the inguinal nodes.
Combined-modality treatment Chemoradiation is the preferred treatment for most patients with anal canal cancer. Investigators from Wayne State University pioneered the use of simultaneous pelvic irradiation and chemotherapy in the treatment of patients with anal canal carcinomas, and demonstrated that the majority of such patients could be treated with this combination, obviating the need for an abdominoperineal esection. The original study design used 3,000 cGy over 3 weeks with 5-FU, 1,000 mg/m˛/d, as a continuous infusion on days 1-4, and repeated on days 29-32. Mitomycin, 15 mg/m˛, was administered as an IV bolus on day 1. Four to 6 weeks after the completion of therapy, patients had a deep muscle biopsy of the anal canal scar.
A randomized trial from the Radiation Therapy Oncology Group (RTOG) showed that the use of mitomycin with radiation and 5-FU increased complete tumor regression and improved colostomy-free survival over radiation and 5-FU alone. At 4 years, colostomy-free survival was higher in the mitomycin arm than in the 5-FU-alone arm (71% vs 59%), as was disease-free survival (73% vs 51%) (Flam MS, John M, Pajak T, et al: J Clin Oncol 114:2527-2539, 1998). An updated analysis of this experience demonstrated that 38 (84%) of 45 patients were rendered disease-free after chemotherapy and irradiation. Individuals who had positive biopsies underwent an abdominoperineal resection.
Because of the success of the above experience, other investigators have attempted to implement infusional 5-FU and mitomycin with radiation as definitive therapy. Most studies have used similar schedules of 5-FU and mitomycin, but have used higher doses of pelvic irradiation (4,500-5,700 cGy). Five-year survival rates > 70% have been reported. Several investigators have compared the results of irradiation alone vs irradiation plus chemotherapy. Cummings et all found that, with identical radiation doses and techniques, the local control rate for cancers > 2 cm in size rose from 49% for radiation alone to 85% when 5-FU and mitomycin were combined with irradiation. Papillion and Montbarbon found an increase in local control from 66% to 81% with a combined-modality approach, compared with pelvic irradiation alone. Two recent ran-domized studies have shown improved local control with chemoradiation over radiation.
Reports of other chemotherapeutic agents in anal cancer have been relatively anecdotal, with limited phase II studies. Because of the activity of cisplatin (Platinol) in other squamous cell carcinomas, this agent has been employed as a single agent or combined with infusional 5-FU in advanced disease.
from the NCI:
Treatment Option Overview
Abdominoperineal resection leading to permanent colostomy was previously thought to be required for all but small anal cancers below the dentate line, with approximately 70% of patients surviving 5 or more years in single institutions,but such surgery is no longer the treatment of choice.Radiation therapy alone may lead to a 5-year survival rate in excess of 70%, although high doses (6,000 cGy or greater) may yield necrosis or fibrosis.Chemotherapy concurrent with lower-dose radiation therapy has a 5-year survival rate in excess of 70% with low levels of acute and chronic morbidity, and few patients require surgery for dermal or sphincter toxic effects.The optimal dose of radiation with concurrent chemotherapy to optimize local control and minimize sphincter toxic effects is under evaluation but appears to be in the 45 Gy to 60 Gy range.Analysis of an intergroup trial that compared radiation therapy plus fluorouracil/mitomycin with radiation therapy plus fluorouracil alone in patients with anal cancer has shown improved results (lower colostomy rates and higher colostomy-free and disease-free survival) with the addition of mitomycin Radiation with continuous infusion of fluorouracil plus cisplatin is also under evaluation. Standard salvage therapy for those patients with either gross or microscopic residual disease following chemoradiotherapy has been abdominoperineal resection. Alternately, patients may be treated with additional salvage chemoradiotherapy in the form of fluorouracil, cisplatin, and a radiation boost to potentially avoid permanent colostomy.
from Feldman: Sleisenger & Fordtran's
Gastrointestinal and Liver Disease, 7th ed.,2002