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Peer-reviewedCC BYInternational journal of molecular sciences

The Enemy of My Enemy: Two Cases of De Novo Metastatic Small-Cell Neuroendocrine Prostate Cancer with BRCA2 Alterations and Brain Metastases.

  • Mads Fallesen Kjer1
  • Mads Hvid Poulsen2,3
  • Sanne Kjær-Frifeldt4
  • Marianne Ingerslev Holt5
  • Mie Holm Vilstrup6
  • Ahmed H Zedan1
6 affiliations
  1. 1Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark.
  2. 2Department for Urology, Esbjerg and Grindsted Hospital, University Hospital of Southern Denmark, 6700 Esbjerg, Denmark.
  3. 3Department of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.
  4. 4Department of Pathology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark.
  5. 5Department of Clinical Genetics, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark.
  6. 6Department of Radiology and Nuclear Medicine, Esbjerg and Grindsted Hospital, University Hospital of Southern Denmark, 6700 Esbjerg, Denmark.
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Abstract

De novo small-cell neuroendocrine prostate cancer (SCNE PC) is a rare and highly aggressive subtype of prostate cancer with limited treatment options. BRCA2 alterations may increase sensitivity to platinum-based chemotherapy and PARP inhibition; however, evidence regarding their clinical relevance in SCNE PC is limited. We present two cases of de novo SCNE PC with distinct BRCA2 alterations. Both patients presented with a similarly extensive disease burden and initially received carboplatin and etoposide (CE), but their clinical courses differed markedly. Patient 1 developed brain metastases three months after completing six cycles of CE and died shortly after rechallenge with CE. In contrast, Patient 2 responded to repeated CE rechallenges, followed by short-term disease control with topotecan and 18 months of disease control with the PARP inhibitor olaparib. He subsequently developed leptomeningeal carcinomatosis and died shortly thereafter, with an overall survival of 5 years and 8 months. These cases illustrate the highly aggressive clinical course of de novo SCNE PC. Despite the potential predictive value of BRCA2 alterations, they may be associated with a higher incidence of brain metastases.

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Cite

BibTeXRIS
BibTeX
@article{kjer2026enemy,
  title = {{The Enemy of My Enemy: Two Cases of De Novo Metastatic Small-Cell Neuroendocrine Prostate Cancer with BRCA2 Alterations and Brain Metastases.}},
  author = {Mads Fallesen Kjer and Mads Hvid Poulsen and Sanne Kjær-Frifeldt and Marianne Ingerslev Holt and Mie Holm Vilstrup and Ahmed H Zedan},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = sep,
  doi = {10.3390/ijms27198453},
  url = {https://europepmc.org/article/MED/42883702},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The Enemy of My Enemy: Two Cases of De Novo Metastatic Small-Cell Neuroendocrine Prostate Cancer with BRCA2 Alterations and Brain Metastases.
AU  - Mads Fallesen Kjer
AU  - Mads Hvid Poulsen
AU  - Sanne Kjær-Frifeldt
AU  - Marianne Ingerslev Holt
AU  - Mie Holm Vilstrup
AU  - Ahmed H Zedan
PY  - 2026
DA  - 2026/09/22
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198453
UR  - https://europepmc.org/article/MED/42883702
AB  - De novo small-cell neuroendocrine prostate cancer (SCNE PC) is a rare and highly aggressive subtype of prostate cancer with limited treatment options. BRCA2 alterations may increase sensitivity to platinum-based chemotherapy and PARP inhibition; however, evidence regarding their clinical relevance in SCNE PC is limited. We present two cases of de novo SCNE PC with distinct BRCA2 alterations. Both patients presented with a similarly extensive disease burden and initially received carboplatin and etoposide (CE), but their clinical courses differed markedly. Patient 1 developed brain metastases three months after completing six cycles of CE and died shortly after rechallenge with CE. In contrast, Patient 2 responded to repeated CE rechallenges, followed by short-term disease control with topotecan and 18 months of disease control with the PARP inhibitor olaparib. He subsequently developed leptomeningeal carcinomatosis and died shortly thereafter, with an overall survival of 5 years and 8 months. These cases illustrate the highly aggressive clinical course of de novo SCNE PC. Despite the potential predictive value of BRCA2 alterations, they may be associated with a higher incidence of brain metastases.
SN  - 1422-0067
ER  -