A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy

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 ) 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 ( = 131, = 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 . The expression of immune-related genes post-nT was investigated ( = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The IS prognostic performance was further assessed in a multicentric cohort ( = 73 patients) treated by Watch-and-Wait. IS positively correlated with the degree of histologic response ( < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT ( = 0.006). IS high identified patients at lower risk of relapse or death compared with IS low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; = 0.009]. Prognostic performance of IS for DFS was confirmed in a validation cohort. IS was an independent parameter, more informative than pre- ( < 0.001) and post-nT ( < 0.05) imaging to predict DFS. IS combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort ( = 73), no relapse was observed in patients with IS high (23.3%). IS 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.