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

Abstract

Introduction: 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.

Case presentation: 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 BRAF ^V600E 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).

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

Keywords: biomarkers; colorectal cancer; immune checkpoint inhibitors; immunotherapy.

Fig. 1. A 1/3 circumscribed, Type II tumor was detected in the ascending colon. The pathology examination result of the biopsy sample was group 5, adenocarcinoma (tub2 >por >muc).

Fig. 2. Findings of upper gastrointestinal endoscopy. Green arrows indicate the area where extramural compression was observed.

Fig. 3. Comparison of pre- and post-immunotherapy on CT scan. (A) Duodenal invasion by the ascending colon cancer. The descending part of the duodenum is at the tip of the red arrow. (B) The tumor has shrunk significantly and a gap was formed between the tumor and the duodenum.

Fig. 4. Histopathological examination of the biopsy tissue reveals moderately differentiated adenocarcinoma characterized by a fused tubular pattern of atypical, well-defined epithelium with notable mucus production (indicated by yellow arrows). The mucus fills the glandular ducts.

Fig. 5. Tumor marker trends in this case.

Fig. 6. Macro and micro images of the specimen obtained after preoperative chemotherapy for ascending colon cancer. In the micro images, the arrows indicate representative areas, and the changes described may not be limited to a single location. (A) There was a 1 cm area of mucosal retraction in the ascending colon (green arrow). (B) Serosal surface: Scarring with serosa retraction is present (blue arrow). (C) Cross-sectional observation: A yellowish-white nodular change (red arrow) of approximately 2 cm, predominantly in the submucosal layer, was observed. (D) Low magnification image of the area marked by the white rectangle in (C). (E) Necrotic lesion suspected to be a consequence of preoperative chemotherapy (purple arrow). No residual viable adenocarcinoma components were observed. Fibrosis is noted in some areas (orange arrow).