Immune Checkpoint Inhibitors for Microsatellite Instability High Unresectable Obstructive Colon Cancer: A Report of Two Cases

Abstract

Introduction: Patients with obstructive colon cancer (OCC) with distant metastases often present with a poor general condition, including malnutrition, anemia, and systemic inflammation. Traditionally, these patients undergo stoma creation and/or primary tumor resection followed by systemic chemotherapy. However, for patients with DNA mismatch repair-deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer, the emergence of immune checkpoint inhibitors (ICIs) has revolutionized treatment strategies, with remarkable antitumor effects. We report two cases of successful management of MSI-H OCC, achieving curative resection while avoiding decompressive procedures, including colostomy creation.

Case presentation: Case 1: A 29-year-old man diagnosed with MSI-H obstructive transverse colon cancer (cT4b stomach, N1b, M1c1) was treated with pembrolizumab monotherapy (200 mg/body, every 3 weeks). The colorectal obstructive scoring system score was 2 at pembrolizumab administration. The patient showed rapid improvement in his abdominal symptoms within 3 days and achieved clinical complete response after eight courses. Laparoscopic partial colectomy with D3 lymph node dissection was subsequently performed safely. He was discharged on postoperative day 8 without postoperative complications. Histopathological analysis confirmed pathological complete response, and the patient was recurrence-free 15 months after surgery without adjuvant chemotherapy. Case 2: A 58-year-old man diagnosed with MSI-H obstructive ascending colon cancer (cT4aN3M1a, LYM) was treated with pembrolizumab monotherapy. The colorectal obstructive scoring system score was 1 at pembrolizumab administration. The patient's abdominal symptoms improved within 5 days, with marked tumor shrinkage after nine courses. Laparoscopic extended right hemi-colectomy with D3 lymph node dissection was subsequently performed safely, and he was discharged on postoperative day 7 without postoperative complications. Histopathological analysis showed major pathological response (less than 10% viable cancer cells in the resected specimen), with no viable tumor cells in the primary lesion. The patient was recurrence-free 1-year post-surgery, without adjuvant chemotherapy.

Conclusions: This report highlights the potential benefits of ICI treatment for dMMR/MSI-H OCC, particularly for rapid relief of obstruction-related symptoms and facilitating oncologically safe R0 resection. In cases of MSI-H OCC, ICIs can be highly effective as an alternative to traditional decompression procedures.

Keywords: MSI-H colorectal cancer; immune checkpoint inhibitors; obstructive colon cancer; pembrolizumab.

Fig. 1. Radiological findings and clinical course in Case 1. (A) Circumferential wall thickening of the transverse colon (yellow arrowheads). (B) Direct invasion of the transverse colon tumor into the stomach (yellow arrows). (C) Severe stenosis was identified by water-soluble contrast medium (white arrowheads). (D) Preoperative clinical course.

CR, complete response; MLBO, malignant large bowel obstruction; PR, partial response

Fig. 2. Clinical complete response was confirmed after eight courses of pembrolizumab in Case 1.

Fig. 3. Laparoscopic partial colectomy (transverse colon) with D3 lymph node dissection in Case 1. (A) Disappearance of direct tumor invasion into the stomach wall. (B) Safe D3 lymph node dissection was possible. (C–E) Macroscopic (C) and histopathological findings ((D), (E); hematoxylin and eosin) showing complete response. Image (E) is a magnified image of the outlined area in image (D).

Panc, pancreas; SMA, superior mesenteric artery; SMV, superior mesenteric vein

Fig. 4. PET-CT findings and clinical course in Case 2. (A) and (B) Pretreatment images. ¹⁸F-FDG accumulation is visible in the main tumor, regional lymph nodes, and para-aortic lymph nodes (red arrows). (C) Preoperative clinical course. (D), (E) After nine courses of pembrolizumab, ¹⁸F-FDG accumulation in the para-aortic lymph nodes disappeared, and only a small degree of ¹⁸F-FDG accumulation was observed in the primary tumor and one regional lymph node (white arrows).

¹⁸F-FDG, fluoro-18-deoxyglucose; MLBO, malignant large bowel obstruction; mFOLFOX6, modified oxaliplatin, leucovorin, and 5-fluorouracil; PET-CT, positron emission tomographycomputed tomography; PR, partial response

Fig. 5. Laparoscopic extended right hemicolectomy with D3 lymph node dissection in Case 2. (A) Owing to severe scarring associated with lymph node shrinkage, the GCT was resected at the root to achieve safe complete mesocolic excision. (B–D) Macroscopic (B) and histopathological findings [(C), (D); hematoxylin and eosin] showing complete response in the primary tumor [image (D) is a magnified image of the outlined area in image (C)].

GCT, gastrocolic trunk; Panc, pancreas; SMA, superior mesenteric artery; SMV, superior mesenteric vein