Multimodal management of primary mixed neuroendocrine prostate cancer with bone flare phenomenon: a rare case report and therapeutic insights

Neuroendocrine prostate cancer (NEPC) is a rare and aggressive subtype of prostate cancer, accounting for approximately 0.5%–2% of cases. Mixed NEPC, composed of both adenocarcinoma and neuroendocrine components, represents a biologically heterogeneous entity with limited clinical experience. A 77-year-old man presented with scrotal swelling, lower urinary tract symptoms, and bilateral leg edema. Imaging demonstrated locally advanced prostate cancer with lymph node and bone metastases. Prostate biopsy revealed mixed neuroendocrine prostate cancer, consisting of neuroendocrine carcinoma and acinar adenocarcinoma (Gleason score 4 + 5=9). Immunohistochemical staining showed absence of RB, PTEN, and p53 protein expression; molecular genetic testing was not performed. The patient was treated with a multimodal regimen including androgen deprivation therapy (ADT), an androgen receptor pathway inhibitor (ARPI), docetaxel chemotherapy, and pelvic radiotherapy. During follow-up, radiographic regression of metastatic lesions and clinical improvement were observed. New bone lesions detected at two months were interpreted as a bone flare phenomenon in the overall clinical context. At seven months of follow-up, the patient remained clinically stable, with PSA levels below 0.1 ng/mL and no evidence of radiographic progression. This report describes the clinical course of a patient with mixed neuroendocrine prostate cancer managed with multimodal therapy and highlights the interpretive challenges associated with imaging changes, including the bone flare phenomenon, during treatment. Given the inherent limitations of a single case, no conclusions regarding treatment efficacy can be drawn. This case underscores the importance of cautious interpretation of PSA kinetics and imaging findings, as well as individualized, multidisciplinary management in this rare and aggressive disease.