POLE and colorectal carcinoma: While somatic POLE mutation portends reduced risk of relapse in stage II CRC, the association with favourable prognosis appears to be lost in stage III disease.20 22 These tumours with a so-called ‘ultramutated’ phenotype may be very responsive to checkpoint inhibition for similar reasons to those thought to underlie the increased sensitivity of dMMR cases.18 Indeed, a recent case report suggests this is the case.23