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

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. 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–  54–60 Gy. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. 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–  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–  54–60 Gy vs. 54 Gy (HR 1.08 [0.97–1.22], P = 0.166). 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.