Radiotherapy alone versus chemoradiotherapy for stage I anal squamous cell carcinoma: a systematic review and meta-analysis

Abstract

Purpose: Patients with stage I anal squamous cell carcinoma (SCC) have been underrepresented in landmark trials showing superiority of chemoradiotherapy over radiotherapy for definitive treatment. This review aims to elucidate whether definitive treatment with radiotherapy versus chemoradiotherapy is associated with differences in survival and treatment-related toxicity outcomes in patients with stage I anal SCC.

Methods: Medline, EMBASE, and CENTRAL were searched as of November 2020 to identify studies comparing outcomes of radiotherapy versus chemoradiotherapy for non-operative treatment of patients with stage I anal SCC. The primary outcomes were 5-year overall survival and 5-year disease-free survival. The secondary outcome was treatment-related toxicities. A pairwise meta-analysis was performed using an inverse-variance random-effects model.

Results: From 2174 citations, 5 retrospective studies with 415 patients treated with radiotherapy and 3784 patients treated with chemoradiotherapy were included. Patients treated with chemoradiotherapy had an increased 5-year overall survival (RR 1.18, 95% CI 1.10-1.26, p < 0.00001, I² = 0%) but no significant difference in 5-year disease-free survival (RR 1.01, 95% CI 0.92-1.11, p = 0.87, I² = 0%). Treatment-related toxicities could not be meta-analyzed due to heterogeneity. Limited data from individual studies suggested an increased frequency of select toxicities with chemoradiotherapy.

Conclusion: Radiotherapy may be an appropriate alternative to chemoradiotherapy for patients with stage I anal SCC who may be unable to tolerate chemotherapy-related toxicity; however, chemoradiotherapy remains the gold standard. Larger prospective studies comparing strategies for this select patient population are needed to clarify whether treatment can be de-escalated.

Keywords: Anal cancer; Chemoradiotherapy; Radiotherapy; Stage I anal SCC; Survival.