- Does the addition of chemotherapy (CT) to radiotherapy (RT) improve outcome for patients with squamous cell cancer of the anal canal? 2. What are the optimal CT drugs for the treatment of patients with squamous cell cancer of the anal canal? 3. Does the use of induction CT before concurrent CT and RT improve outcome for patients with squamous cell cancer of the anal canal? 4. What is the best management for patients with squamous cell cancer of the anal canal who are human immunodeficiency virus (HIV) positive?
Outcomes of interest are colostomy rate, local failure, survival, disease-free survival, acute and late adverse effects, and quality of life.

# TARGET POPULATION
These recommendations apply to adult patients (age 18 years) with a primary diagnosis of biopsy-proven squamous cell cancer of the anal canal, including basaloid, cloacogenic, and transitional cell tumours. These recommendations do not apply to patients who have previously undergone resection of their tumour. The management of patients who later develop extra-pelvic metastases is not considered in this guideline.
- For all stages of localized squamous cell cancer of the anal canal, concurrent CT and RT is recommended over RT alone to improve local control and decrease colostomy rates. - The optimal CT drug combination for squamous cell cancer of the anal canal is 5fluorouracil (5FU) plus mitomycin C (MMC), given concurrently with radiation treatment. - At this time, induction CT before concurrent CT and RT should be considered an investigational approach. - It is the expert opinion of the Gastrointestinal Cancer Disease Site Group (GI DSG) that HIV-positive patients with squamous cell cancer of the anal canal should be managed in the same way as patients without known HIV. Treating physicians should be aware that a greater than average risk of toxicity is possible.

# QUALIFYING STATEMENTS
- No randomized controlled trials (RCTs) were identified that addressed the management of squamous cell cancer of the anal canal in HIV-positive patients. See the Discussion in Section 2 for a description of non-randomized data available on this topic. - Only two RCTs included patients with T1 lesions of the anal canal, and results were not reported by disease stage. See the Discussion in Section 2 for further discussion on management of patients with T1N0 disease. - Two RCTs included patients with squamous cell cancer of the perianal skin. A limited discussion of perianal cancer is included in the Discussion in Section 2.
- James et al. 2013 (ACT II), studied maintenance chemotherapy versus none following chemoradiation and found that maintenance chemotherapy does not improve overall survival or colostomy-free survival. Therefore, maintenance chemotherapy following chemoradiation is not recommended in the management of squamous cell carcinoma of the anal canal. See Section 4 for more details.
- In the trials using MMC in the 5FU-MMC combination regimens, MMC schedules include dose of 12 or 15mg/me day 1 only, and a 10mg/m2 Day 1, 29 dosing. There is no comparative data to allow a recommendation of a preferred schedule.

# KEY EVIDENCE
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