Management of Squamous Cell Carcinomas of the Anal Canal and Anal Margin After Failure of Chemoradiotherapy Treatment: A Narrative Review.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with an increasing incidence despite advancements in treatment. The primary treatment for localized ASCC is radiochemotherapy (RCT), which achieves high rates of tumor regression in most cases, but up to 30% of patients experience recurrence or persistent disease. Salvage surgery, such as an abdominoperineal resection (APR), is often used for recurrent disease but is associated with significant morbidity and limited oncological outcomes. Patients with small T1 tumors may also benefit from primary local excision. For patients with metastatic or unresectable recurrent ASCC, chemotherapy, particularly carboplatin and paclitaxel, remains the standard treatment. New therapeutic strategies, including immune checkpoint inhibitors like pembrolizumab, are showing promise, particularly in PD-L1-positive tumors. Clinical trials have suggested that immunotherapy offers a potential alternative for patients for whom conventional treatments have failed, though the overall response rates remain modest. Re-radiation and intraoperative radiotherapy combined with salvage surgery may improve the outcomes for select patients, though the data are still limited. The management of recurrent or persistent ASCC requires a personalized approach, incorporating both established and emerging therapies to optimize patient outcomes. Further research is needed to refine these treatment strategies.