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Background  Patients with colorectal carcinoma and high‐grade microsatellite instability (MSI‐H) or deficiency in mismatch repair (dMMR) exceptionally respond to immune checkpoint inhibitors (ICIs). ICIs are more active in treatment‐naïve patients than in patients with refractory MSI‐H/dMMR metastatic colorectal cancer and even more active in patients with locally advanced tumors.    Material and Methods  A 33‐year‐old male patient with Lynch syndrome was diagnosed with a locally advanced rectal cancer and refused standard neoadjuvant chemoradiation because of the potential harm of sexual dysfunction. MMR and microsatellite instability status were analyzed by immunohistochemistry and fragment length polymerase chain reaction followed by capillary electrophoresis.    Results  After MSI‐H/dMMR was confirmed, the patient was treated with ICIs (1 mg/kg ipilimumab at day 1 and 3 mg/kg nivolumab at day 1 and 15). A complete clinical response was documented at day 21 after start of treatment. The patient underwent a total mesorectal excision at day 30. In the extirpated tissue, a complete pathological response was confirmed.    Conclusion  In MSI‐H/dMMR locally advanced rectal cancer short‐course ICI treatment is highly effective and may be discussed in patients with dMMR locally advanced rectal cancer.    Key Points    Immune checkpoint inhibitors are more active in treatment‐naïve patients than in patients with refractory high‐grade microsatellite instability (MSI‐H)/deficiency in mismatch repair (dMMR) colorectal cancer.  Standard neoadjuvant chemoradiation is less effective in MSI‐H/dMMR rectal cancer patients than in patients with proficient mismatch repair.  A young patient with Lynch syndrome and MSI‐H/dMMR locally advanced rectal cancer refused chemoradiation in order to preserve his fertility.  After neoadjuvant treatment with one dose of ipilimumab and two doses of nivolumab a complete clinical and pathological response was documented.  Clinical trials are needed to first establish neoadjuvant treatment with immune checkpoint inhibitors in patients with locally advanced MSI‐H/dMMR rectal cancer and thereafter to evaluate organ‐preservation strategies.

the oncologist

Complete Pathological Response After Neoadjuvant  Short‐Course  Immunotherapy with Ipilimumab and Nivolumab in Locally Advanced  MSI‐H / dMMR  Rectal Cancer