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

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.