Radiation Therapy Dose in Anal Cancer: Patterns of Care and Survival

Abstract

Definitive chemoradiotherapy represents standard of care treatment for localized squamous cell cancer of the anus. National Comprehensive Cancer Network (NCCN) guidelines recommend a minimum of 45 Gy and escalation to 54-59 Gy for advanced disease. Per the Phase II clinical trial RTOG 0529, 50.4 Gy was prescribed for T2N0 disease, and 54 Gy for T3-T4 and/or node-positive (N+) disease. We sought to compare utilization practice and survival based on radiotherapy (RT) dose. The hypothesis was that dose escalation above 54 Gy was not associated with improved survival. The National Cancer Database (NCDB) was queried to identify patients with non-metastatic squamous cell cancer of the anus from 2004-2013 treated with chemoradiotherapy. Patients were stratified into four groups based on the RT dose received: 40-<45 Gy, 45-<50 Gy, 50-54 Gy and >54-60 Gy. Subgroup analysis was conducted to evaluate survival based on RT dose, as recommended by RTOG 0529, for early (T1-2N0) and locally advanced (T3-T4 and/or N+) disease. The Kaplan-Meier method was used to estimate overall survival (OS) for each group. Hazard ratios (HR) were computed using Cox regression modeling. Of 8,005 patients identified, median age was 58 years and 29.7% were male. For both early and locally advanced disease, the most commonly prescribed RT dose was 54 Gy. After a median follow-up of 40.3 months, 1,949 deaths were reported with a 5-year OS of 73.4%. Five-year OS was 60.3% for the 40-<45 Gy group, compared to 73.1%, 74.9%, and 72.5% for the 45-<50, 50-54 and >54-60 Gy groups, respectively (p<0.0001). On multivariate analysis (MVA) adjusting for age, gender, race, insurance, income, education, Charlson-Deyo score, year of diagnosis, clinical T and N stage, facility characteristics, and tumor grade, RT dose of 40-<45 Gy had significantly worse survival compared to 50-54 Gy (HR 1.81 [95% confidence interval: 1.41-2.34], p<0.0001). Compared to 50-54 Gy, there was no significant difference in survival for patients who received 45-<50 Gy (HR 1.10 [0.93-1.29], p=0.27) or >54-60 Gy (HR 1.03 [0.91-1.15], p=0.67). For early disease, 5-year OS for patients was 81.4%, 81.3%, and 81.7% for patients receiving 45-<50, 50-51, and >51-60 Gy, respectively (p=0.85). MVA showed no significant difference in survival based on dose for these patients. For locally advanced disease, 5-year OS was 64.6%, 68.9%, 65.0% for <54, 54, and >54 Gy groups, respectively (p=0.19). On MVA, 54 Gy was associated with significantly higher survival compared to <54 Gy (HR 1.17 [1.01-1.37], p=0.038] but not >54 Gy (HR 1.12 [0.97-1.29], p=0.12). In this NCDB study, 54 Gy was the most utilized RT dose for anal cancer regardless of T or N stage. RT doses of ≥45 Gy were associated with improved OS overall. For locally advanced disease, 54 Gy but not >54 Gy was associated with improved OS. Thus, doses of 45 Gy and 54 Gy for early and locally advanced disease, respectively, may be adequate without dose-escalation to 59 Gy.