Unanticipated pathological clearance in two cases of clinical T4b dMMR/MSI-h advanced colorectal cancer: the potential of immune checkpoint inhibitors despite positive positron-emission tomography results

Daigaku Nakamura; Takeshi Yanagita; Yoshiaki Fujii; Kaori Watanabe; Takuya Suzuki; Hajime Ushigome; Ruriko Nishigaki; Naomi Sugimura; Mamoru Tanaka; Ryo Ogawa; Hiroki Takahashi; Takaya Shimura; Yuji Hotta; Yoichi Matsuo; Masahiro Kondo; Yoko Furukawa-Hibi; Shuji Takiguchi

doi:10.1186/s40792-024-01894-x

Unanticipated pathological clearance in two cases of clinical T4b dMMR/MSI-h advanced colorectal cancer: the potential of immune checkpoint inhibitors despite positive positron-emission tomography results

Surg Case Rep. 2024 May 1;10(1):105. doi: 10.1186/s40792-024-01894-x.

Authors

Daigaku Nakamura¹, Takeshi Yanagita², Yoshiaki Fujii³, Kaori Watanabe³, Takuya Suzuki³, Hajime Ushigome³, Ruriko Nishigaki⁴, Naomi Sugimura⁴, Mamoru Tanaka⁴, Ryo Ogawa³, Hiroki Takahashi³, Takaya Shimura⁴, Yuji Hotta⁵, Yoichi Matsuo³, Masahiro Kondo⁵, Yoko Furukawa-Hibi⁵, Shuji Takiguchi³

Affiliations

¹ Department of Pharmacy, Nagoya City University Hospital, Kawasumi 1, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8602, Japan.
² Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya City, Aichi, 467-8601, Japan. tyanagi@med.nagoya-cu.ac.jp.
³ Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya City, Aichi, 467-8601, Japan.
⁴ Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
⁵ Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.

Abstract

Background: The standard treatment for colorectal cancer consists of surgery and chemotherapy, which can be combined to improve outcomes. Immune checkpoint inhibitors (ICI) are a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair (dMMR). However, limited data are available about the use of ICI in the neoadjuvant and conversion settings. Here, we present two cases treated with ICI.

Case presentation: Case 1: A 75-year-old male with a large, borderline resectable rectal cancer diagnosed as cT4bN1bM0 who underwent neoadjuvant chemotherapy, followed by combination ICI consisting of ipilimumab and nivolumab. After four courses of ICI, the tumor significantly shrank, but positron emission tomography still showed a positive result and R0 resection was performed. Pathological analysis revealed no residual cancer cells. The patient has been monitored without adjuvant chemotherapy, and no recurrences have occurred after one year. Case 2: A 60-year-old male with locally advanced sigmoid colon cancer who received neoadjuvant treatment with pembrolizumab. The tumor partially shrank after three courses, and continued pembrolizumab monotherapy resulted in further tumor shrinkage which still showed positive positron emission tomography. Curative sigmoidectomy with partial resection of the ileum and bladder was performed, and the pathological outcome was pCR. There was no viable tumor in the specimen. The patient has been monitored without adjuvant chemotherapy for six months, and no recurrence has been observed.

Conclusions: The present study reports two cases, including a large, borderline resectable rectal cancer after failure of chemotherapy followed by combination treatment with nivolumab and ipilimumab and one case of sigmoid colon cancer after pembrolizumab treatment, which resulted in pathological complete response. However, it remains unknown whether ICI therapy can replace surgery or diminish the optimal extent of resection, or whether adjuvant chemotherapy is needed after surgery in the case of achieving pCR after ICI therapy. Overall, this case report suggests that ICI before colorectal surgery can be effective and potentially a 'watch-and-wait" strategy could be used for cases in which ICI is effective.

Keywords: Case report; Colorectal cancer; Immune checkpoint inhibitor; Immunotherapy; Microsatellite instability; Mismatch repair deficient; Neoadjuvant; Positive positron emission tomography.