Cancer treatment paradigms may shift dramatically if immunotherapy can replace chemotherapy for certain colon cancer patients, potentially eliminating the harsh side effects that accompany traditional cytotoxic drugs while maintaining or improving survival outcomes. The AZUR-2 trial represents a pivotal test of this hypothesis in patients whose tumors carry specific genetic signatures that make them highly responsive to immune checkpoint inhibitors. This global Phase III study is enrolling adults with Stage III or high-risk Stage II colon adenocarcinoma characterized by deficient mismatch repair mechanisms or high microsatellite instability. The trial randomizes participants 2:1 to receive either dostarlimab immunotherapy before and after surgery, or immediate surgery followed by standard adjuvant chemotherapy. The experimental arm delivers dostarlimab at 500mg every three weeks for four cycles pre-surgery, then 1000mg every six weeks for six cycles post-surgery. The significance extends beyond colon cancer treatment protocols. This tumor subtype, representing roughly 15% of colon cancers, exhibits exceptional sensitivity to PD-1 inhibitors due to high mutational burden and neoantigen presentation. Early-phase neoadjuvant studies with similar immunotherapies have demonstrated remarkable pathological complete response rates, sometimes exceeding 90% in this population. However, the transition from promising early-phase data to definitive Phase III evidence remains critical. The trial's primary endpoint of event-free survival, assessed by independent review, will determine whether immunotherapy monotherapy can match or surpass chemotherapy's established survival benefits. Success could establish a new standard eliminating chemotherapy-related neuropathy, fatigue, and immune suppression for thousands of patients annually, while failure would reinforce the continued necessity of cytotoxic approaches despite their considerable toxicity profile.