Optimal Radiotherapy Dose in Anal Cancer: Trends in Prescription Dose and Association with Survival

Purpose Definitive chemoradiotherapy represents a standard of care treatment for localized anal cancer. National Comprehensive Cancer Network guidelines recommend radiotherapy (RT) doses of >= 45 Gy and escalation to 50.4-59 Gy for advanced disease. Per RTOG 0529, 50.4 Gy was prescribed for early-stage disease (cT1-2N0), and 54 Gy for locally advanced cancers (cT3-T4 and/or node positive). We assessed patterns of care and overall survival (OS) with respect to the RT dose. Methods The National Cancer Database identified patients with non-metastatic anal squamous cell carcinoma from 2004 to 2015 treated with chemoradiotherapy. Patients were stratified by RT dose: 40-< 45, 45-< 50, 50-54, and > 54-60 Gy. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. Results A total of 10,524 patients were identified with a median follow-up of 40.7 months. The most commonly prescribed RT dose was 54 Gy. On multivariate analysis, RT doses of 40-< 45 Gy were associated with worse OS vs. 50-54 Gy (HR 1.68 [1.40-2.03],P < 0.0001). There was no significant difference in OS for patients who received 45-< 50 or > 54-60 Gy compared with 50-54 Gy. For early-stage disease, there was no significant association between RT dose and OS. For locally advanced disease, 45-< 54 Gy was associated with worse survival vs. 54 Gy (HR 1.18 [1.04-1.34],P = 0.009), but no significant difference was detected comparing > 54-60 Gy vs. 54 Gy (HR 1.08 [0.97-1.22],P = 0.166). Conclusions For patients with localized anal cancer, RT doses of >= 45 Gy were associated with improved OS. For locally advanced disease, 54 Gy but not > 54 Gy was associated with improved OS.