Neoadjuvant Immune Checkpoint Inhibition Improves Organ Preservation in T4bm0 Colorectal Cancer With Mismatch Repair Deficiency: A Retrospective Observational Study.

Colorectal cancer patients with mismatch repair deficiency are usually less aggressive and associated with lower risk of distant metastasis. Immune checkpoint inhibition, rather than traditional chemoradiotherapy, has shown great advantages in treating such patients.This study aimed to verify our hypothesis that locally very advanced (T4b) CRC without distant metastases might present with higher probability of dMMR and be more sensitive to neoadjuvant immune checkpoint inhibition.This study was designed as a single center retrospective observational study.The study was conducted in a tertiary referral center in China.Patients clinically diagnosed as T4bM0 CRC from 2008 to 2019 were included.Clinicopathological characteristics, MMR status and survival outcomes of dMMR patients were analyzed.A total of 268 patients were included. The incidence of dMMR in T4bM0 population was 27.6% (75/268), with 84.0% (63/75) in colon and 16.0% (12/75) in rectum. For tumors located in proximal colon, 45.0% (50/111) exhibited dMMR, while the incidence of dMMR in sigmoid colon cancer and rectal cancer was only 15.9% (25/157). Neoadjuvant immune checkpoint inhibition significantly reduced open surgery and multivisceral resection rate (p = 0.000 and p = 0.025, respectively). The pCR rate in neoadjuvant immune checkpoint inhibition group was significantly higher than that in neoadjuvant chemoradiotherapy/ chemotherapy group (70.0% v.s. 0%, p = 0.004). No tumor downstaging was observed after neoadjuvant chemotherapy. Neoadjuvant immune checkpoint inhibition provided significantly better disease-free survival (p = 0.0078) and relatively longer overall survival (p = 0.15) than other groups.This study is limited by the possible selection bias and small sample size.Our data depicted the high incidence of dMMR in T4bM0 CRC and the effectiveness of neoadjuvant immune checkpoint inhibition group in organ preservation. Precision oncology requires identification of MMR protein status at initial diagnosis to make rational treatment decision for these special patients. See Video Abstract at http://links.lww.com/DCR/B952.