Clinical Outcomes, Patterns of Failure, and Salvage Therapies of a Large Modern Cohort of Patients With Anal Squamous Cell Carcinoma Treated With Definitive-Intent Intensity-Modulated Radiation Therapy

Abstract

PurposePatterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy are not well described. Patients and MethodsWe identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure (LRF), distant failure (DF), progression-free survival (PFS), colostomy-free survival (CFS), and overall survival (OS)), patterns of failure, and salvage therapies were collected. Failures were analyzed by competing risks methods, whereas survival endpoints were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months from completing IMRT. Results375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for AJCC stage 0-I, II, and III, respectively. Six-year rates of LRF, DF, PFS, CFS, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse six-year OS than patients without LRF (44% versus 86%, P<0.0001). Approximately 30% of patients who underwent salvage therapy were alive ten years after recurrence, compared with none of the patients who were managed with chemotherapy alone or best supportive care. ConclusionsThis large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment.