Nonoperative Management of Early-Stage dMMR Tumors Offers Organ Preservation

A phase 2 trial with 117 patients having stage I–III mismatch repair-deficient (dMMR) solid tumors, including locally advanced rectal and other nonrectal cancers, evaluated neoadjuvant PD-1 blockade with dostarlimab. In cohort 1 (rectal cancer), all 49 patients who achieved a clinical complete response opted for nonoperative management, with 75% sustaining this response at 12 months. In cohort 2, 35 of 54 patients achieved a complete response, and most also chose to avoid surgery. Overall, 82 out of 103 treatment completers preserved their organs, with a 2-year recurrence-free survival rate of 92% and predominantly low-grade, reversible adverse events.

The results demonstrate that neoadjuvant PD-1 blockade can effectively replace surgery in early-stage dMMR tumors, offering a promising strategy to maintain organ function while achieving high rates of long-term disease control.