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...

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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
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1642412/full
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Summary: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.
ISSN:2234-943X