Rectal cancer
ICD-10 C20 · ICD-11 2B92

Treatment of Locally Advanced Rectal Cancer with dMMR or MSI-H Status

Locally advanced rectal cancer encompassing the upper, middle, or lower third of the rectum represents a broad clinical challenge, but a molecularly defined subset — tumours that are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) — warrants a distinct treatment pathway.

Clinical Scenario
dMMR / MSI-H
Treatment Approach (Overview)

For this population, the recommended approach involves PD-1-blocking monoclonal antibody immunotherapy. The full protocol details the specific agent, planned treatment course, and criteria for response assessment.

Complete regimen, duration, and evidence grading are available in the full protocol below.

Treatment Goals

The primary objective is a sustained clinical complete response (cCR), evaluated through MRI, endoscopy, and digital rectal examination (DRE). Restaging is performed at structured intervals following treatment initiation — at 12 weeks and again at 24 weeks.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.annonc.2025.05.528

  1. Patients with locally advanced dMMR or MSI-H tumours in the upper, middle or lower third of the rectum should receive dostarlimab for a planned treatment duration of 6 months [II, A; ESCAT score: I-B; not European Medicines Agency (EMA) or Food and Drug Administration (FDA) approved in this setting].
  2. Approximately 2%-3% of rectal cancers are dMMR and/or MSI-H, which are associated with a poor response to ChT in the neoadjuvant treatment of colon cancer.
  3. Patients received dostarlimab, a PD-1-blocking mAb, for 6 months.
  4. 12 weeks after initiation of dostarlimab in patients with dMMR or MSI-H tumours and a second restaging 24 weeks after initiation of immunotherapy [III, A].
  5. The most recent presentation of data from this trial reported that, of 48 patients with dMMR rectal cancers, all patients (42/42) who completed the planned 6-month treatment with dostarlimab achieved a cCR.
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