Microsatellite Instability in Colorectal Cancer: The Evolving Role of Immunotherapy

A 57-year-old man presented with right-sided abdominal pain. CT imaging showed a large, locally advanced right-sided colon tumor with extension into the retroperitoneum and right abdominal wall. The tumor appeared necrotic with possible superimposed infection (Fig. 1). He denied any family history of cancer. He was hospitalized and managed nonoperatively with bowel rest and antibiotics. During his hospital stay, a colonoscopy was performed, showing a large mass in the ascending colon; biopsies came back positive for invasive adenocarcinoma. Mismatch repair (MMR) testing revealed a deficiency in expressions of MLH1 and PMS2, with hypermethylation of MLH1. Furthermore, genetic testing for hereditary colon cancer was negative. He had no evidence of metastatic disease on axial imaging. Given the extent of the tumor and concern for the inability to attain negative margins with resection, we discussed with medical oncology initiating neoadjuvant treatment, including immunotherapy. The patient received 6 cycles of immunotherapy with pembrolizumab. His posttreatment scans showed remarkable tumor regression (Fig. 2). Given the sporadic nature of the patient’s tumor, a segmental colectomy was recommended. After the surgery, his pathology revealed a near complete pathologic response with minimal intramucosal adenocarcinoma (3 mm focus), negative margins, and 0/34 positive lymph nodes.