A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal...

No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (IS_B) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait").

Biopsies from two independent cohorts (n ₁ = 131, n ₂ = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3⁺ and CD8⁺ T cells and quantified by digital pathology to determine IS_B. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The IS_B prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait.

IS_B positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). IS_B high identified patients at lower risk of relapse or death compared with IS_B low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P = 0.009]. Prognostic performance of IS_B for DFS was confirmed in a validation cohort. IS_B was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. IS_B combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n = 73), no relapse was observed in patients with IS_B high (23.3%).

IS_B predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.