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

Purpose: 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 and materials: We included 181 patients with LARC from a single subcenter of a prospective study comparing total neoadjuvant therapy (TNT) based on short-course radiation therapy with long-term chemoradiation therapy (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 ratio. 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 values of mIS_b and diagnostic biopsy immunoscore 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 < .001), whereas a weak correlation was witnessed between CD8+ and CD8/CD3 ratio (R = 0.45). The 3-year disease-free survival 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 = .01), whereas diagnostic biopsy immunoscore failed to distinguish survival outcomes. Multivariate analysis revealed mIS_b to be an independent prognostic factor for disease-free survival in surgically treated patients (P = .01). Specifically, patients with high mIS_b score showed longer progression-free survival than other subgroups in the TNT cohort (P = .049), but no significant difference was found in the CRT population.

Conclusions: In this study, mIS_b demonstrated significant prognostic value in patients with LARC receiving preoperative therapies, especially in the TNT subgroup. These findings may help tailor the intensity of neoadjuvant therapy for patients.