S3980 Endoscopic Submucosal Dissection of T3 MSI-high Colorectal Cancer Treated With Neoadjuvant Pembrolizumab

Introduction: Immunotherapy (ICI) with programmed death 1 blockade such as pembrolizumab has been efficacious in treating early-stage deficient DNA mismatch repair (dMMR) and microsatellite instability-high (MSI-H) colorectal tumors. Interestingly, this therapy has been reported to cause significant regression of colorectal cancer. Here we report a case of an elderly patient with locally invasive colon cancer (T3N0M0), that was treated with pembrolizumab and endoscopic submucosal dissection. Case Description/Methods: An 88-year-old man with medical history of hypertension, atrial fibrillation with pacemaker and multiple colonic polyps since index colonoscopy at age 58. Surveillance colonoscopy on June 6, 2024, found a 3 cm friable ascending colon mass with pathology confirming invasive moderately differentiated adenocarcinoma, MSI-H with loss of MLH1 and PMS2. He started on first line treatment with single agent pembrolizumab on August 7, 2024. Within 2 months, there was a decrease in size of the lesion from 3 cm to 1.9 cm and no increase in size or evidence of metastasis at 8 months. Colonoscopy performed to assess treatment response showed a polypoid non-obstructing 3 cm ascending colon mass with an adjacent tattoo. Biopsies revealed sessile serrated lesion with high grade dysplasia and no malignancy noted. The case was discussed at multidisciplinary tumor board and since he was not a surgical candidate, the decision was made to attempt endoscopic resection. The residual mass was then resected successfully with endoscopic submucosal dissection (ESD). A 4 cm by 4 cm resection specimen was obtained; the specimen was removed en-bloc. The margins were free of polypoid tissue. Pathology showed minute focus of invasive adenocarcinoma without evidence of lymphovascular invasion. Discussion: dMMR and MSI-H tumors account for 15% of all colorectal cancers. Immunotherapy has the potential to change the standard of care for localized dMMR tumors as it has shown high rates of pathologic, radiographic, and endoscopic response. As a result, organ-sparing strategies including endoscopic resection with ESD are becoming feasible management options for these lesions that previously required invasive surgical resection.