Abstract: Objective To explore the treatment strategy for patients with locally advanced rectal cancer harboring a POLE proofreading deficiency mutation. Methods The clinical data of a patient with locally advanced rectal cancer carrying the POLE p.V411L mutation was analyzed. Results The patient was a 41-year-old male with mismatch repair-proficient locally advanced rectal cancer. After initially receiving neoadjuvant concurrent chemoradiotherapy, laparoscopic exploration revealed that the tumor was unresectable. Subsequent genetic testing identified a POLE proofreading deficiency mutation with a tumor mutational burden of 426 mut/MB. The patient then underwent two years of treatment with envafolimab, achieving long-term complete clinical remission. Conclusions Colorectal cancer with POLE proofreading deficiency mutation is highly sensitive to immunotherapy. Genetic testing should be considered to screen for POLE proofreading deficiency mutations and other immunotherapy-sensitive variants in cases where rectal cancer invades surrounding tissues or organs, or when organ function preservation is a concern during surgery.

Key words: rectal cancer, POLE mutation, immunotherapy, complete remission