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

## TL;DR

This review discusses treatment options for anal squamous cell carcinoma that recurs or persists after initial therapy, focusing on surgery, chemotherapy, and emerging immunotherapy.

## Contribution

The paper provides a narrative review of evolving therapeutic strategies for managing recurrent anal squamous cell carcinoma after chemoradiotherapy failure.

## Key findings

- Salvage abdominoperineal resection is used for recurrent disease but has significant morbidity.
- Chemotherapy with carboplatin and paclitaxel is standard for metastatic or unresectable ASCC.
- Immunotherapy like pembrolizumab shows promise in PD-L1-positive tumors but with modest response rates.

## Abstract

Anal squamous cell carcinoma (ASCC) presents a challenge in clinical practice due to its rarity and its multifaceted management. This comprehensive narrative review focuses more particularly on therapeutic strategies in cases of recurrence or persistence following the initial therapy. Drawing insights from recent studies, this review explores the role of salvage abdominoperineal resection (APR), chemotherapy, radiotherapy, and immunotherapy for optimizing outcomes. By synthesizing the current evidence and discussing emerging trends, this review aims to provide an understanding of the evolving strategies for managing ASCC.

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.