Anti-PD-1-based immunotherapy as curative-intent treatment in dMMR/MSI-H rectal cancer: A multicentre cohort study

Eur J Cancer. 2022 Oct:174:176-184. doi: 10.1016/j.ejca.2022.07.016. Epub 2022 Aug 26.


Background: In a portion of patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer, clinical complete response (cCR) could be achieved after anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. However, no data are available concerning the safety of omitting surgery and adopting immunotherapy as a curative-intent treatment for these patients.

Methods: We retrospectively collected a series of patients with dMMR/MSI-H rectal adenocarcinoma who had cCR after receiving anti-PD-1 immunotherapy and adopted immunotherapy as curative-intent treatment from six institutions. Survival outcomes were analysed using the Kaplan-Meier method.

Results: Nineteen patients were included with a median age of 48 (range 19-63). One patient was diagnosed with stage I disease, four with stage II disease and fourteen with stage III disease. Sixteen patients received anti-PD-1 immunotherapy as the first line of therapy, and eleven patients were treated with single-agent anti-PD-1 antibodies. The median time from the start of treatment to cCR was 3.8 (range 0.7-6.5) months. During a median follow-up of 17.1 (range 3.1-33.5) months since achieving cCR, no local or distant relapse was observed. Two-year local recurrence-free survival, distant metastasis-free survival, disease free-survival and overall survival for the whole cohort were 100%, 100%, 100% and 100%, respectively.

Conclusions: For patients with dMMR/MSI-H locally advanced rectal cancer who achieved cCR during anti-PD-1 immunotherapy, adopting immunotherapy as curative-intent treatment might be an alternative option. Longer follow-up and larger cohorts are warranted to verify this innovative treatment approach.

Keywords: Anti-PD-1 immunotherapy; Curative-intent; Organ preservation; Rectal cancer; dMMR/MSI-H.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Colorectal Neoplasms* / pathology
  • DNA Mismatch Repair
  • Humans
  • Immunotherapy
  • Microsatellite Instability
  • Neoplasm Recurrence, Local
  • Rectal Neoplasms* / genetics
  • Rectal Neoplasms* / therapy
  • Retrospective Studies