Radiation Therapy for Anal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline

This guideline provides evidence-based recommendations addressing the indications for definitive treatment of primary squamous cell carcinoma of the anal canal and anal margin.

The American Society for Radiation Oncology convened a task force to address 4 key questions focused on (1) indications for radiation therapy (RT), concurrent systemic therapy and local excision/surgery, (2) appropriate RT techniques, (3) appropriate RT dose-fractionation regimens, target volumes, and dose constraints, and (4) appropriate surveillance strategies after definitive treatment. Recommendations are based on a systematic literature review and created using a predefined consensus-based methodology and system for grading evidence quality and recommendation strength.

Multidisciplinary evaluation and decision-making are recommended for all patients. Definitive treatment with combined modality therapy is recommended for most patients using concurrent 5-fluorouracil or capecitabine plus mitomycin, with cisplatin as a conditional alternative to mitomycin with RT. Select patients with early-stage disease may be considered for local excision alone. RT target volumes should include the primary tumor/anal canal and rectum, and mesorectal, presacral, internal and external iliac, obturator, and inguinal lymph nodes. Intensity modulated RT-based treatment approaches are recommended. The primary tumor should receive doses of 4500 to 5940 cGy in 25 to 33 fractions, and clinically involved lymph nodes should receive 5040 to 5400 cGy in 28 to 30 fractions, depending on disease stage and RT approach. Elective nodal volumes should receive 3600 to 4500 cGy in 20 to 30 fractions, depending on disease stage and RT approach. Dose guidance for normal tissues and measures to minimize acute and chronic treatment-related toxicity are provided. Treatment breaks should be minimized. Posttreatment surveillance strategies, including timing of clinical/digital exam, anoscopy, computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography, are discussed.

These evidence-based recommendations guide clinical practice on the use of definitive therapy for localized anal squamous cell carcinoma. Future studies will further refine the optimal RT dose for early- and advanced-stage disease, use of alternative systemic agents, including immunotherapy, the role of adaptive RT, and other strategies to minimize long-term treatment-related toxicity.