Evolving landscape of biomarkers in colorectal cancer: From interleukin-8 to integrated multi-marker strategies

Figure 1 This sequential algorithm illustrates a stepwise approach to integrating established and emerging biomarkers into clinical decision-making for colorectal cancer. Mismatch repair status is the first and most critical step, directing patients with deficient mismatch repair tumors toward immunotherapy (neoadjuvant or adjuvant). For proficient mismatch repair/microsatellite stable tumors, RAS/BRAF mutational status and tumor laterality refine prognosis. Perioperative carcinoembryonic antigen provides additional risk stratification, with high-normal levels (≥ 2.1 ng/mL) warranting closer surveillance. Where available, postoperative circulating tumor DNA enables dynamic risk assessment and treatment adjustment, with the DYNAMIC-III trial demonstrating safe de-escalation in circulating tumor DNA-negative patients. Interleukin-8 remains investigational, with potential complementary value in selected subgroups. All decisions should be made in a multidisciplinary team context, weighing all factors. Interleukin-8 is presented as an investigational biomarker and should not be interpreted as a clinically validated marker. CRC: Colorectal cancer; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; MSI-H: Microsatellite instability-high; MSS: Microsatellite stable; CEA: Carcinoembryonic antigen; ctDNA: Circulating tumor DNA; IL-8: Interleukin-8.