Preoperative, biopsy-based assessment of the tumour microenvironment in patients with primary operable colorectal cancer

The tumour microenvironment (TME) is recognised as an important prognostic characteristic and therapeutic target in patients with colorectal cancer (CRC). However, assessment generally utilises surgically resected specimens, precluding neoadjuvant targeting. The present study investigated the feasibility of intra-epithelial CD3⁺ T-lymphocyte density and tumour stroma percentage (TSP) assessment using preoperative colonoscopic biopsies from 115 patients who had undergone resection of stages I-III CRC, examining the relationship between biopsy and surgically resected specimen-based assessment, and the relationship with cancer-specific survival (CSS). High biopsy CD3⁺ density was associated with high CD3⁺ density in the invasive margin, cancer stroma and intra-epithelial compartments of surgically resected specimens (area under the curve > 0.62, p < 0.05 for all) and with high Immunoscore. High biopsy TSP predicted high TSP in resected specimens (p = 0.001). Intra-class correlation coefficient for both measures was >0.7 (p < 0.001), indicating excellent concordance between individuals. Biopsy CD3⁺ density (hazard ratio [HR] 0.23, p = 0.002) and TSP (HR 2.23, p = 0.029) were independently associated with CSS; this was comparable to the prognostic value of full section assessment (HR 0.21, p = 0.004, and HR 2.25, p = 0.033 respectively). These results suggest that assessment of the TME is comparable in biopsy and surgically resected specimens from patients with CRC, and biopsy-based assessment could allow for stratification prior to surgery or commencement of therapy targeting the TME.