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

Background: The purpose of this study was to assess the prognostic significance of the modified diagnostic biopsy-adapted immunoscore (mIS_b) in determining the outcomes for patients with locally advanced rectal cancer (LARC) in a neoadjuvant setting.

Methods: We 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 mIS_b 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 mIS_b and IS_b for survival outcomes, and to assess the role of mIS_b in TNT and CRT subgroups respectively.

Results: In 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 mIS_b groups respectively (P=0.01), while IS_b failed to distinguish survival outcomes. Multivariate analysis revealed mIS_b to be an independent prognostic factor for DFS in surgically treated patients (P=0.01). Specifically, patients with high mIS_b score showed longer PFS than other subgroups in the TNT cohort (P=0.049), but no significant difference was found in the CRT population.

Conclusions: In this study, mIS_b 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.