Prognostic Role and Time Varying Failure Hazard of Neoadjuvant Rectal (NAR) Scores in the Stellar Randomized Phase 3 Trial

Abstract

This study examined the prognostic role of the neoadjuvant rectal (NAR) score on disease-free survival (DFS) in the STELLAR phase III trial and assessed time-varying failure hazard. The study included patients from the STELLAR trial who underwent total mesorecta excision and had calculable NAR scores. Chi-square tests were used to analyze the distribution of demographic information, treatment information, and NAR scores. Kaplan-Meier and Cox regression analyses assessed DFS, while smoothed hazard plots evaluated hazard variations. Of 461 patients, 231 received total neoadjuvant therapy (TNT) and 229 received concurrent chemoradiotherapy (CRT). With a median follow-up of 37 months, 3-year DFS rates for low, intermediate, and high NAR scores were 86.2%, 72.671.8%, and 53.153.6%, respectively (P <0.001). In the TNT group, rates for the corresponding NAR score groups were 87.3%, 67.6%, and 52.4% while in the CRT group, rates were 84.7%, 76.0%, and 53.4% (both P <0.001). Multivariate analysis showed NAR scores as independent prognostic factors for DFS (intermediate vs. low, hazard ratio (HR) = 2.452.55, 95% confidence interval (CI): 1.347 - 4.4675, P <0.003; high vs. low, HR = 4.2668, 95% CI: 2.5133 - 8.727.79, P <0.001). The DFS hazardrisk rates for different NAR score groups initially increased and then decreased, peaking in the second year with rates of 5.04.6%, 11.62%, and 21.52% for low, intermediate, and high NAR scores, respectively. After the fourth year, the high NAR score still had a higher failure hazardrisk (12.5%), while the intermediate and low NAR score had a lower relapse hazardrisk (<3%). The NAR score was a strong prognostic factor for DFS in the STELLAR trial, irrespective of TNT or CRT modalities. Hazard variations at different NAR score levels offer insights for personalized monitoring and warrant further investigation in clinical trials using NAR scores as endpoints. (NCT02533271).