The Role of Multiagent Chemoradiation in the Management and Prognosis of Anal Squamous Cell Carcinoma

Introduction: The standard treatment for anal squamous cell carcinoma (ASCC) is multiagent chemotherapy with radiation (CRT). This is based on several randomized trials demonstrating lower recurrence and colostomy-free survival rates with multiagent CRT; however, these studies could not confirm an overall survival (OS) benefit. We hypothesized that the lack of improved OS was due to limited sample sizes and follow-up, and that multiagent CRT is associated with higher OS. Methods: The National Cancer Database was queried for patients diagnosed with stages I, II, and II ASCC and received between 45 and 59.4 Gy of radiation between 2004 and 2015. OS of patients receiving multiagent CRT compared to monoagent CRT and radiation alone was analyzed across stages. Results: A total of 10,438 patients received multiagent CRT, 1163 had monoagent CRT and 446 received radiation alone. Compared to the other two groups, patients receiving multiagent CRT were younger, had fewer comorbidities, and more advanced disease (all p < 0.001). After adjusting for available confounders, multiagent CRT remained independently associated with higher OS for stages II and III ASCC. A subset analysis of patients ≥ 70 years demonstrated similar survival between monoagent versus multiagent CRT across all stages. Conclusion: Multiagent CRT is associated with an OS benefit compared to monoagent CRT or radiation alone for stages II and III, but not stage I ASCC. Monoagent CRT may represent an adequate treatment for selected patients ≥ 70 years. The benefit of multiagent CRT should be balanced against treatment-related toxicities depending on disease stage and patient physiology.