Should rectal cancer be regarded as a different tumor entity from left-sided colon cancer? A clinical and molecular NGS-based study of 552 cases

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors and BRAF in right-sided tumors. Mutations in KRAS,NRAS, and BRAF were not detected in 28.6% of patients with right-sided tumors and in 45% of patients with left-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Tumors located in the rectum differed from those in other locations in biology, site of metastasis (lung), and mutation rates (e.g., BRAF, FBXW7, and TP53). KRAS, NRAS, and BRAF gene mutations were not detected in >47% of rectal tumors compared with 42.8% of left-sided and 28.6% of right-sided tumors. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.