Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: The intergroup trial (RTOG 98-11)

BACKGROUND: Only 4 prospective randomized phase 3 trials have been reported for anal cancer. A prognostic factor analysis for anal cancer from a prospective database has been published from only 1 study (N = 110). To confirm and uncover new prognostic factors,we analyzed the prospective database of intergroup RTOG 98-11. METHODS: Univariate and multivariate analyses of the baseline characteristics for 5-year overall survival (OS) and disease-free survival (DFS) were carried out. Various combinations of tumor diameter and clinically positive nodes (N⁺) were analyzed to identify subgroups. RESULTS: A total of 644 were assessable and analyzed. Tumor diameter >5 cm was associated with poorer 5-year DFS (P = .0003) and poorer 5-year OS (P = .0031), and N⁺ was associated with poorer 5-year DFS (P ≤ .0001) and poorer 5-year OS (P = ≤ .0001) in the multivariate analysis. In stratified analyses, N⁺ had more adverse influence on DFS and OS than did tumor diameter. Patients with >5-cm tumor and N⁺ had the worst DFS (only 30% at 3 years compared with 74% for the best group; <5 cm primary and N0) and OS (only 48% at 4 years compared with 81% for the best group; <5 cm primary and N0). Men had worse DFS (P = .02) and OS (P = .016). These factors maintained their influence in each treatment arm. CONCLUSIONS: This prospective prognostic factor analysis establishes tumor diameter as an independent prognosticator of poorer 5-year DFS and OS and confirms N ⁺ and male sex as poor prognostic factors. This analysis also uncovers novel subgroups (derived from combining prognostic factors) with incremental worsening of DFS and OS.