# Successful Treatment of Locally Advanced Microsatellite Instability-High Ascending Colon Cancer Using an Immune Checkpoint Inhibitor without Extensive Resection: A Case Report

## TL;DR

A patient with advanced colon cancer successfully responded to immunotherapy before surgery, avoiding major organ removal.

## Contribution

Demonstrates successful preoperative immunotherapy in a locally advanced, microsatellite instability-high colon cancer case.

## Key findings

- Immune checkpoint inhibitors significantly reduced tumor size, enabling standard surgery.
- Complete tumor disappearance was confirmed in postoperative pathological analysis.
- Neoadjuvant immunotherapy may reduce surgical invasiveness in colorectal cancer.

## Abstract

Colorectal cancer is a prevalent malignancy that necessitates personalized chemotherapy, especially with the advent of molecular-targeted drugs and immune checkpoint inhibitors. In Japan, immune checkpoint inhibitors have been approved for unresectable advanced and recurrent colorectal cancer; however, their use in preoperative therapy for colorectal cancer has not yet been approved. Globally, neoadjuvant immunotherapy has demonstrated promising outcomes in colorectal cancer cases with high immunogenicity, including microsatellite instability-high and deficient mismatch repair.

We report a case of a microsatellite instability-high, clinically unresectable, locally advanced ascending colon cancer treated with immune checkpoint inhibitors, which showed significant tumor shrinkage, facilitating standard surgery while avoiding adjunct organ resection. The patient, a 70-year-old male, experienced chronic abdominal pain and diarrhea. Lower gastrointestinal endoscopy and computed tomography confirmed a diagnosis of ascending colon cancer with suspected invasion into the descending duodenum. Although curative resection was technically feasible with pancreatoduodenectomy, neoadjuvant chemotherapy was selected to reduce tumor size, considering the patient’s overall condition. Companion diagnostics revealed microsatellite instability-high status and BRAFV600E mutation, leading to the initiation of chemotherapy combined with an immune checkpoint inhibitor (pembrolizumab). Subsequently, prolonged pembrolizumab administration was challenging due to suspected immune-related adverse events, including diarrhea and pruritus. However, significant tumor reduction was observed during a follow-up computed tomography scan, facilitating surgery approximately 6 months after treatment initiation. The perioperative period was uneventful, and the patient was discharged on the eighth day after operation. The final pathological results revealed complete tumor disappearance (histological effect of chemotherapy: Grade 3).

This case highlights the potential of neoadjuvant immunotherapy in reducing surgical invasiveness in patients with colorectal cancer.