Comparison of 7th and 8th Editions of the AJCC TNM Staging Classification System for Anal Canal Cancer: A Multi-Institutional External Validation Study

Abstract

Accurate cancer staging is essential to determine extent of disease, to implement a treatment plan, and to inform prognosis. Recently, the American Joint Committee on Cancer (AJCC) 8th edition (AJCC 8) has updated its anal cancer staging system to reflect changes in definitions of N stage, and consequently changes in definitions of overall stage groupings. The present study aims to validate the new AJCC 8 prognostic staging system using a provincial, multi-institutional cohort of anal cancer patients, and to compare its performance with the previous AJCC 7 staging system. Patients with anal carcinoma treated with curative intent chemoradiotherapy in Alberta, Canada from 2000 to 2017 were identified from a prospectively maintained database. Demographic, disease, and treatment-related data were abstracted. Patients were reclassified as per AJCC 8, and descriptive statistics were calculated. Kaplan-Meier curves of progression free survival (PFS) and overall survival (OS) were evaluated for statistical difference using the log-rank method. Cox proportional hazards regression was used to evaluate the predictive performance of both AJCC 7 and 8 staging systems. Akaike information criterion (AIC) was applied to correct for potential bias in comparing prognostic systems with a different number of stage groupings. A smaller AIC value indicates a superior model for predicting outcomes. Each model's ability to distinguish overall stage groupings and N stage definitions were considered significant at a value of p<0.05. For the 285 eligible patients, median age was 58.0 years, 73.0% were female, 89.1% had squamous cell carcinoma histology, 36.8% were clinically lymph node positive, and 26.3% had clinical T stage ≥T3. After a median follow-up of 5.7 years, 11.9% had distant progression only, 4.4% had local progression only, and 3.9% progressed locally and distantly. Compared with the previous edition, AJCC 8 upstaged 27.0% of patients, and downstaged 8.1%. AJCC 8’s overall stage groupings had modestly better predictive performance for PFS (AIC 656.2, p=0.001) and OS (AIC 956.2, p<0.001), compared to AJCC 7 (PFS: AIC 656.5, p<0.001; and OS: AIC 956.7, p<0.001). However, AJCC 8’s new N stage definitions provided more accurate stratification for PFS (AIC 651.2, p<0.001) and OS (AIC 977.9, p=0.010), compared to AJCC 7’s previous N stage definitions (PFS: AIC 661.2, p=0.012; and OS: AIC 978.9, p=0.059). This is the largest cohort study to validate both AJCC 7 and 8 staging systems for anal cancer. Overall stage groupings in AJCC 8 showed modest improvements in predictive ability compared to AJCC 7. Although both staging systems performed well, the new definitions of N stage introduced in AJCC 8 more accurately predict survival outcomes for anal cancer patients, and thereby supports its use in clinical practice.