Intensity-Modulated Radiation Therapy for Anal Cancer

ABSTRACT: The contemporary treatment of anal cancer is combined-modality therapy with radiation therapy, fluorouracil, and mitomycin. This therapy results in long-term disease-free survival and sphincter preservation in the majority of patients. Tempering these positive results is the high rate of treatment-related morbidity associated with chemoradiation therapy for anal cancer. The use of intensity-modulated radiation therapy (IMRT) has the potential to reduce acute and chronic treatment-related toxicity, minimize treatment breaks, and potentially improve disease-related outcomes by permitting radiation dose escalation in selected cases.

Historically, the treatment of squamous cell carcinoma of the anal canal has been an abdominoperineal resection (APR), resulting in loss of the anus and rectum with need for a permanent colostomy. In addition to loss of sphincter function, high rates of urinary/sexual dysfunction, wound morbidity, and perioperative mortality have been reported. Studies evaluating outcomes following APR reported 5-year survival rates of 30% to 71%, with locoregional recurrence occurring in 19% to 45% of patients.[1,2]

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Randomized Trials for Anal Cancer: Toxicity and Disease-Related Outcomes

Given these poor results, Nigro and coinvestigators from Wayne State University treated three patients with low-dose (30 Gy) preoperative radiation therapy concurrently with continuous-infusional fluorouracil (5-FU) and mitomycin followed by APR. The surgical specimens of two patients showed no evidence of residual disease, whereas a third patient refused surgery and remained disease-free.[3] Since this report, similar studies have confirmed high rates of clinical and pathologic response using preoperative chemoradiotherapy and surgery,[4-8] leading to trials evaluating radiation therapy alone or combined chemoradiation as primary radical therapy, with surgery reserved for salvage. These studies demonstrated that the majority of patients treated by these approaches achieved long-term disease-free survival without surgery.

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