Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report

Pembrolizumab has emerged as a significant therapeutic option for the treatment of solid tumors with a high tumor mutational burden (TMB-high). However, there have been no reports of its use in treatment-related neuroendocrine prostate carcinoma (t-NEPC) with TMB-high. We present the case of a 66-ye...

Full description

Saved in:
Bibliographic Details
Main Authors: Keiji Shiba, Motohiro Fujiwara, Ayaka Onuki, Daisuke Kato, Takeshi Shirakawa, Yohei Shimizu, Takumasa Amemiya, Tsunehiro Nenohi, Yuki Matsumoto, Masayasu Urushibara, Hideto Kano, Kazuhiro Ishizaka, Mikiko Takahashi, Minato Yokoyama
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1642412/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849247522791358464
author Keiji Shiba
Motohiro Fujiwara
Ayaka Onuki
Daisuke Kato
Takeshi Shirakawa
Yohei Shimizu
Takumasa Amemiya
Tsunehiro Nenohi
Yuki Matsumoto
Masayasu Urushibara
Hideto Kano
Kazuhiro Ishizaka
Mikiko Takahashi
Minato Yokoyama
author_facet Keiji Shiba
Motohiro Fujiwara
Ayaka Onuki
Daisuke Kato
Takeshi Shirakawa
Yohei Shimizu
Takumasa Amemiya
Tsunehiro Nenohi
Yuki Matsumoto
Masayasu Urushibara
Hideto Kano
Kazuhiro Ishizaka
Mikiko Takahashi
Minato Yokoyama
author_sort Keiji Shiba
collection DOAJ
description Pembrolizumab has emerged as a significant therapeutic option for the treatment of solid tumors with a high tumor mutational burden (TMB-high). However, there have been no reports of its use in treatment-related neuroendocrine prostate carcinoma (t-NEPC) with TMB-high. We present the case of a 66-year-old man with metastatic prostate cancer (adenocarcinoma with a Gleason score of 4 + 5, initial prostate-specific antigen [PSA] level of 267 ng/mL, clinical stage T3bN0M1b) who was initially treated with doublet therapy, including apalutamide and leuprorelin, leading to a reduction in circulating levels of PSA < 0.001 ng/mL. However, 35 months after diagnosis, a retroperitoneal mass developed and neuron-specific enolase (NSE) levels were elevated 62.6 ng/mL. Computed tomography-guided biopsy of the tumor confirmed metastasis of t-NEPC, while genetic profiling revealed a TMB-high status. Pembrolizumab treatment was initiated at the 39-month after diagnosis. At the 41-month after diagnosis, a 75% reduction in the retroperitoneal mass and a decrease in NSE levels to 31 ng/mL were observed. This case suggests that pembrolizumab is a potential treatment option for t-NEPCs with TMB-high.
format Article
id doaj-art-d3bf28d9478345aa8ddf1b13c823d092
institution Kabale University
issn 2234-943X
language English
publishDate 2025-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-d3bf28d9478345aa8ddf1b13c823d0922025-08-20T03:58:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16424121642412Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case reportKeiji Shiba0Motohiro Fujiwara1Ayaka Onuki2Daisuke Kato3Takeshi Shirakawa4Yohei Shimizu5Takumasa Amemiya6Tsunehiro Nenohi7Yuki Matsumoto8Masayasu Urushibara9Hideto Kano10Kazuhiro Ishizaka11Mikiko Takahashi12Minato Yokoyama13Department of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Pathology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanDepartment of Urology, Teikyo University Hospital, Mizonokuchi, Kawasaki, Kanagawa, JapanPembrolizumab has emerged as a significant therapeutic option for the treatment of solid tumors with a high tumor mutational burden (TMB-high). However, there have been no reports of its use in treatment-related neuroendocrine prostate carcinoma (t-NEPC) with TMB-high. We present the case of a 66-year-old man with metastatic prostate cancer (adenocarcinoma with a Gleason score of 4 + 5, initial prostate-specific antigen [PSA] level of 267 ng/mL, clinical stage T3bN0M1b) who was initially treated with doublet therapy, including apalutamide and leuprorelin, leading to a reduction in circulating levels of PSA < 0.001 ng/mL. However, 35 months after diagnosis, a retroperitoneal mass developed and neuron-specific enolase (NSE) levels were elevated 62.6 ng/mL. Computed tomography-guided biopsy of the tumor confirmed metastasis of t-NEPC, while genetic profiling revealed a TMB-high status. Pembrolizumab treatment was initiated at the 39-month after diagnosis. At the 41-month after diagnosis, a 75% reduction in the retroperitoneal mass and a decrease in NSE levels to 31 ng/mL were observed. This case suggests that pembrolizumab is a potential treatment option for t-NEPCs with TMB-high.https://www.frontiersin.org/articles/10.3389/fonc.2025.1642412/fullpembrolizumabprostate cancertumor mutational burdentreatment-related neuroendocrine prostate carcinomaimmune checkpoint inhibitors
spellingShingle Keiji Shiba
Motohiro Fujiwara
Ayaka Onuki
Daisuke Kato
Takeshi Shirakawa
Yohei Shimizu
Takumasa Amemiya
Tsunehiro Nenohi
Yuki Matsumoto
Masayasu Urushibara
Hideto Kano
Kazuhiro Ishizaka
Mikiko Takahashi
Minato Yokoyama
Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report
Frontiers in Oncology
pembrolizumab
prostate cancer
tumor mutational burden
treatment-related neuroendocrine prostate carcinoma
immune checkpoint inhibitors
title Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report
title_full Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report
title_fullStr Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report
title_full_unstemmed Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report
title_short Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report
title_sort pembrolizumab for treatment related neuroendocrine prostate carcinoma with a high tumor mutational burden a case report
topic pembrolizumab
prostate cancer
tumor mutational burden
treatment-related neuroendocrine prostate carcinoma
immune checkpoint inhibitors
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1642412/full
work_keys_str_mv AT keijishiba pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT motohirofujiwara pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT ayakaonuki pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT daisukekato pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT takeshishirakawa pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT yoheishimizu pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT takumasaamemiya pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT tsunehironenohi pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT yukimatsumoto pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT masayasuurushibara pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT hidetokano pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT kazuhiroishizaka pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT mikikotakahashi pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport
AT minatoyokoyama pembrolizumabfortreatmentrelatedneuroendocrineprostatecarcinomawithahightumormutationalburdenacasereport