Treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC) is a rare and highly aggressive transformation of prostate adenocarcinoma following long-term androgen deprivation therapy (ADT). This variant is marked by an aggressive clinical course, significant heterogeneity, rapid visceral metastasis, and resistance to hormonal therapy.

A 77-year-old male presented in April 2019 with symptoms of poor urinary stream and hematuria. Initial investigations identified Gleason 4+5 prostate adenocarcinoma with an index PSA of 90 ng/mL. The patient underwent prostate EBRT and three years of ADT, achieving an initial PSA reduction to 0.01 ng/mL. However, in July 2022, he developed a low rectal mass and bleeding. Histopathology from a bladder-preserving pelvic exenteration revealed small-cell neuroendocrine carcinoma with extensive local invasion and regional nodal metastases. Over the next year, he experienced progressive visceral disease, including pelvic collections with fistulation, new lung metastases, and malignant enterocutaneous suprapubic and perineal fistulas. Despite multiple surgeries, palliative chemotherapy with etoposide and cisplatin, and subsequent treatment with pembrolizumab, the disease continued to progress. He was transitioned to best supportive care and succumbed to his disease in June 2024.

 

This case underscores the aggressive nature of treatment-emergent small-cell neuroendocrine prostate cancer, a serious complication of ADT in prostate adenocarcinoma. The transformation to t-SCNC presents significant therapeutic challenges, with a poor prognosis and limited response to conventional treatments. This case highlights the urgent need for further research into the pathogenesis of neuroendocrine differentiation and the development of more efficacious treatment strategies for this aggressive cancer variant.