What is the workup and treatment for anal (anorectal) cancer?

From the Guidelines

The workup and treatment of anal cancer should begin with a thorough history, physical examination, and staging, followed by combined chemoradiation therapy as the standard treatment for most anal cancers, as recommended by the most recent guidelines 1. The diagnosis of anal cancer requires a biopsy of the suspicious area, and staging involves CT scans of the chest, abdomen, and pelvis, pelvic MRI to assess local invasion, and PET-CT to evaluate for metastatic disease. HIV testing is also recommended as HIV-positive patients have higher incidence rates.

• The standard treatment for most anal cancers is combined chemoradiation therapy, known as the Nigro protocol, which consists of 5-fluorouracil (5-FU) given as a continuous infusion at 1000 mg/m²/day on days 1-4 and 29-32, along with mitomycin C at 10 mg/m² on days 1 and 29, concurrent with radiation therapy (total dose of 45-54 Gy) 1.
• This approach avoids the need for abdominoperineal resection and permanent colostomy in most patients, with cure rates of 70-90% for localized disease.
• For patients who cannot tolerate mitomycin C, cisplatin can be substituted at 75 mg/m² on days 1 and 29 1.
• Surgery is typically reserved for small (<1 cm) perianal lesions or for salvage therapy in cases of persistent or recurrent disease after chemoradiation.
• Close follow-up is essential, with clinical examinations every 3-6 months for 5 years, including digital rectal examination and anoscopy to monitor for recurrence 1. The most recent guidelines from 2025 1 prioritize a multidisciplinary approach, including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, for treating patients with anal carcinoma.
• The guidelines recommend chemoradiation therapy with at least 45 Gy, infused FU and MMC, as the standard treatment of stage II or higher anal canal tumors, with a boost of 15-20 Gy applicable in certain cases 1.
• The guidelines also emphasize the importance of complete response as an outcome of interest, as complete responders to definitive chemoradiation may be able to avoid abdominoperineal resection and permanent colostomy 1.

From the Research

Workup and Treatment of Anal Cancer

• The standard treatment for anal cancer is concurrent chemoradiotherapy with 5-fluorouracil (5-FU) and mitomycin-C (MMC) 2.
• The treatment outcomes for patients with anal cancer can be measured by progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), and colostomy-free survival (CFS) 2.
• A study comparing one versus two cycles of MMC in conjunction with 5-FU and radiation therapy found no significant difference in PFS, CSS, OS, or CFS between the two groups 2.
• Another study used a regimen of 5-FU and cisplatin in combination with radiation therapy, resulting in a complete regression rate of 94% and a local recurrence rate of 6% 3.
• The use of intensity-modulated radiation therapy (IMRT) and PET scans for staging and response assessment may help decrease treatment-related toxicity and improve therapeutic efficacy 4.

Chemotherapy Regimens

• 5-FU and MMC are commonly used in the treatment of anal cancer, with or without radiation therapy 2, 5.
• Cisplatin can be used as an alternative to MMC in combination with 5-FU and radiation therapy 3, 6.
• The efficacy of 5-FU and MMC in the second-line treatment of metastatic squamous cell carcinomas of the anal canal has been evaluated, with a reported objective response rate of 26.4% and a median progression-free survival of 3 months 5.

Radiation Therapy

• Radiation therapy is an essential component of the treatment of anal cancer, with the goal of preserving the sphincter and achieving local control 4.
• Advanced radiation therapy techniques, such as IMRT, can help reduce treatment-related toxicity and improve therapeutic efficacy 4.
• The use of PET scans for staging and response assessment can help guide radiation therapy and improve treatment outcomes 4.