Long-term results from the NICHE-2 phase 2 trial indicate that short-course immunotherapy can produce deep, durable responses in dMMR colon cancer. In 111 patients treated with four weeks of neoadjuvant nivolumab plus ipilimumab, none experienced disease recurrence at a median follow-up of 58.7 months. The readout reinforces interest in neoadjuvant immunochemotherapy strategies aimed at maximizing pathologic response while potentially reducing the need for extended treatment. For clinicians and trial designers, the next questions center on whether durability holds across broader histologic and molecular subgroups and how response can be monitored outside the operating room. The trial’s long follow-up also raises the bar for comparators in future studies exploring non-escalation approaches in biomarker-defined populations.