[Prognostic and Predictive Value of a Modified Diagnostic Biopsy-Adapted Immunoscore in Patients with Rectal Cancer After Neoadjuvant Treatment- a translational study from the STELLAR trial]

Abstract

BackgroundThe purpose of this study was to assess the prognostic significance of the modified diagnostic biopsy-adapted immunoscore (mISb) in determining the outcomes for patients with locally advanced rectal cancer (LARC) in a neoadjuvant setting. MethodsWe included 181 LARC patients from a single subcenter of a prospective study comparing total neoadjuvant therapy (TNT) based on short-course radiotherapy with long-term chemoradiotherapy (CRT). Tumor biopsies at baseline were stained for CD8+ and CD3+ T-cell densities. The mISb was developed using mean percentile of CD8+ T-cell density and CD8/CD3 ratios. Patients were classified into low (0%-25%), intermediate (>25%-70%), and high (>70%-100%) in both groups. The relativity among different lymphocytes and their correlation with survival were illustrated. Survival analyses and Cox regression models were used to compare the prognostic value of mISb and ISb for survival outcomes, and to assess the role of mISb in TNT and CRT subgroups respectively. ResultsIn this study, 151 (83.4%) patients received surgery and 30 (16.6%) followed a watch and wait strategy. A strong correlation was found between CD8+ and CD3+ T-cell densities (R=0.86, P<0.001), while a weak correlation witnessed between CD8+ and CD8/CD3 ratio (R=0.45). The 3-year disease-free survival (DFS) for the entire cohort was 69.9%, with 57.2%, 68.6%, and 85.5% for the low, intermediate, and high mISb groups respectively (P=0.01), while ISb failed to distinguish survival outcomes. Multivariate analysis revealed mISb to be an independent prognostic factor for DFS in surgically treated patients (P=0.01). Specifically, patients with high mISb score showed longer PFS than other subgroups in the TNT cohort (P=0.049), but no significant difference was found in the CRT population. ConclusionsIn this study, mISb demonstrates significant prognostic value in LARC patients receiving preoperative therapies, especially in the TNT subgroup. These findings may help tailor the intensity of neoadjuvant therapy for patients.