De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

SIMPLE SUMMARY: Management of early-stage squamous cell carcinoma of the anus (SCCA) remains controversial. The current standard of care treatment of chemotherapy combined with radiation therapy can result in both acute and late toxicity. Alternative therapies, including radiation therapy alone or local excision, may be less toxic, but the role of these therapies in early-stage SCCA remains unclear. Additional options for reducing the intensity of therapy for early-stage SCCA include reduction of radiation dose, altering treatment volumes, modifying chemotherapy type and dosage, and using intensity-modulated radiation therapy to reduce the radiation dose to adjacent normal tissues. Multiple prospective studies are actively investigating the role of de-escalation of therapy in patients with early-stage SCCA. ABSTRACT: The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.