This protocol addresses locally advanced rectal cancer — in the upper, middle, or lower third of the rectum — that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), after a planned course of dostarlimab has not produced a sustained clinical complete response.
Locally advanced dMMR or MSI-H rectal cancer in the upper, middle, or lower third of the rectum. Approximately 2%–3% of rectal cancers carry the dMMR/MSI-H profile, and these tumours are associated with a poor response to chemotherapy in the neoadjuvant setting.
The first-line approach was dostarlimab, a PD-1-blocking monoclonal antibody, for a planned duration of 6 months. Escalation to this protocol is triggered by failure to achieve — or sustain — a clinical complete response (cCR), as assessed by MRI, endoscopy, and digital rectal examination at restaging at 12 weeks and again at 24 weeks after initiation of immunotherapy.
When tumour persistence or local recurrence is confirmed, a surgical intervention may be considered as the next step. Multidisciplinary team discussion is recommended to evaluate further treatment options. The full decision algorithm and complete protocol detail are available via the link below.
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].
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.
Salvage resection is recommended in case of tumour persistence or local recurrence [IV, A].
MDT discussion is recommended to consider adjuvant ChT or CRT, according to clinical risk assessment [III, A].
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