A case of microsatellite instability-high clinically advanced castration-resistant prostate cancer showing a remarkable response to pembrolizumab sustained over at least 18 months.

Abstract

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2 Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.

• Authors: Kosuke Shimizu, Takeshi Sano, Kei Mizuno, Takuro Sunada, Noriyuki Makita, Hiroki Hagimoto, Takayuki Goto, Atsuro Sawada, Masakazu Fujimoto, Kentaro Ichioka, Osamu Ogawa, Takashi Kobayashi, Shusuke Akamatsu
• Journal: Cold Spring Harbor molecular case studies (Cold Spring Harb Mol Case Stud) Vol. 8 Issue 4 (06 2022) ISSN: 2373-2873 [Electronic] United States
• PMID: 35487690 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Shimizu et al.; Published by Cold Spring Harbor Laboratory Press.

Chemical References

• Antibodies, Monoclonal, Humanized
• pembrolizumab
• MutS Homolog 2 Protein

Topics

• Antibodies, Monoclonal, Humanized
• Humans
• Male
• Microsatellite Instability
• MutS Homolog 2 Protein (genetics)
• Prostatic Neoplasms, Castration-Resistant (drug therapy, genetics)
• Transurethral Resection of Prostate