Skip to main content


Log in

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability

  • Case Report
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript


Pembrolizumab is a novel immune-checkpoint inhibitor used for treatment of microsatellite instability-high (MSI-H) colorectal cancer. Several studies have reported clinical complete response (CR) after treatment with pembrolizumab, but none has confirmed pathological CR. Here we provide the first description of pathological CR with R0 resection after immune-checkpoint therapy. A 45-year-old man presented at our hospital with abdominal distention and highly elevated tumor markers. Contrast-enhanced abdominal CT showed a 110 × 75 mm bulky mass with markedly swollen lymph nodes and an isolated peritoneal metastasis in the pelvic space. Biopsy revealed poorly differentiated adenocarcinoma. We diagnosed ascending colon cancer cT4aN2bM1c Stage IVc. A biopsy specimen obtained during systemic chemotherapy (FOLFOXIRI) was confirmed pathologically as MSI-H, after which the treatment was changed to pembrolizumab. The tumor markers rapidly decreased to within normal ranges after three courses of treatment. After twenty courses, CT revealed shrinkage of the main tumor, lymph node metastases, and the peritoneal metastasis, and we performed extended right hemi-colectomy with dissection of the peritoneal metastasis. No residual tumor cells were found histologically. The patient achieved pathological CR and the postoperative course was uneventful. An accurate diagnosis and appropriate follow up are crucial for obtaining sufficient therapeutic effect of pembrolizumab.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others


  1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    PubMed  Google Scholar 

  2. Benson AB 3rd, Venook AP, Cederquist L, et al. Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology. J Natl Comp Canc Netw. 2017;15:370–98.

    Article  CAS  Google Scholar 

  3. Daly MC, Paquette IM. Surveillance, epidemiology, and end results (SEER) and SEER-Medicare databases: use in clinical research for improving colorectal cancer outcomes. Clin Colon Rectal Surg. 2019;32:61–8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Le DT, Kim TW, Van Cutsem E, et al. Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 2020;38:11–9.

    Article  CAS  PubMed  Google Scholar 

  7. Andre T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. NEJM. 2020;383:2207–18.

    Article  CAS  PubMed  Google Scholar 

  8. Koopman M, Kortman GA, Mekenkamp L, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100:266–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang C, Sandhu J, Fakih M. Complete response to pembrolizumab in a patient with metastatic colon cancer with microsatellite instability and a history of Guillain-Barre syndrome. J Gastrointest Oncol. 2019;10:161–5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Keating M, Giscombe L, Tannous T, et al. Prolonged treatment response to pembrolizumab in a patient with pretreated metastatic colon cancer and lynch syndrome. Case Rep Oncol Med. 2019;2019:3847672.

    PubMed  PubMed Central  Google Scholar 

  11. Kieler M, Scheithauer W, Zielinski CC, et al. Case report: impressive response to pembrolizumab in a patient with mismatch-repair deficient metastasized colorectal cancer and bulky disease. ESMO Open. 2016;1:e000084.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lemery S, Keegan P, Pazdur R. First FDA approval agnostic of cancer site—when a biomarker defines the indication. N Engl J Med. 2017;377:1409–12.

    Article  PubMed  Google Scholar 

  13. Delaunoit T, Alberts SR, Sargent DJ, et al. Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741. Ann Oncol. 2005;16:425–9.

    Article  CAS  PubMed  Google Scholar 

  14. Lam VW, Spiro C, Laurence JM, et al. A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases. Ann Surg Oncol. 2012;19:1292–301.

    Article  PubMed  Google Scholar 

  15. Nicholson BD, Shinkins B, Pathiraja I, et al. Blood CEA levels for detecting recurrent colorectal cancer. Cochrane Database Syst Rev. 2015;2015:cd011134.

    PubMed Central  Google Scholar 

  16. Kalff V, Duong C, Drummond EG, et al. Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery. J Nucl Med. 2006;47:14–22.

    PubMed  Google Scholar 

  17. van Stiphout RG, Lammering G, Buijsen J, et al. Development and external validation of a predictive model for pathological complete response of rectal cancer patients including sequential PET-CT imaging. Radiother Oncol. 2010;98:126–33.

    Article  PubMed  Google Scholar 

  18. Karamchandani DM, Chetty R. Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective. J Clin Pathol. 2018;71:665–71.

    Article  CAS  PubMed  Google Scholar 

  19. Verschuren EC, van den Eertwegh AJ, Wonders J, et al. Clinical, endoscopic, and histologic characteristics of ipilimumab-associated colitis. Clin Gastroenterol Hepatol. 2016;14:836–42.

    Article  PubMed  Google Scholar 

  20. Chen JH, Pezhouh MK, Lauwers GY, et al. Histopathologic features of colitis due to immunotherapy with anti-PD-1 antibodies. Am J Surg Pathol. 2017;41:643–54.

    Article  PubMed  Google Scholar 

  21. Gonzalez RS, Salaria SN, Bohannon CD, et al. PD-1 inhibitor gastroenterocolitis: case series and appraisal of “immunomodulatory gastroenterocolitis.” Histopathology. 2017;70:558–67.

    Article  PubMed  Google Scholar 

  22. Xing P, Zhang F, Wang G, et al. Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis. J Immunother Cancer. 2019;7:341.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Tetsuro Tominaga.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human/animal rights

All procedures followed were in accordance with the ethical standards of our Institutional Review Board and with the Helsinki Declaration of 1975, as revised in 2008(5).

Informed consent

Informed consent was obtained from the patient for inclusion in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tominaga, T., Nonaka, T., Fukuda, A. et al. Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability. Clin J Gastroenterol 15, 134–139 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: