Neoadjuvant immunotherapy for dMMR/MSI-H locally advanced rectal cancer patients: demystifying the 100% clinical complete response paradigm

: Six months of treatment with dostarlimab followed by non-operative management in case of clinical complete response (cCR) is the new standard-of-care for patients with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) locally advanced rectal cancer (LARC). The most recent update of the seminal phase II trial by Cercek et al. shows a cCR rate of 100% that allowed sparing chemoradiation and surgery to all included patients. Here, we present three clinical cases of patients with dMMR and MSI-H LARC treated with neoadjuvant dostarlimab at three Italian institutions with radiological evidence of disease progression while on treatment and discuss potential similarities among them to understand when and how this apparently rare event may occur.