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Background: Small cell neuroendocrine prostate cancer (SCNC) is a rare aggressive type of neuroendocrine prostate cancer (NEPC) characterized by aggressive clinical course and lack of response to hormone therapy. Case Description: We present a case report of a 60-year-old man diagnosed with a histologically confirmed primary metastatic (bone, lymph nodes and visceral) SCNC with small components of an adenocarcinoma with clinical symptoms mimicking an acute prostatitis. Of note, serum based neuroendocrine markers (carcinoembryonic antigen, chromogranin A) were negative and the patient had a prostate-specific antigen (PSA) elevation. Genetic testing of tumor tissue revealed breast cancer gene 2 (BRCA2) copy number loss and a retinoblastoma gene (RB1) mutation reflecting again the aggressiveness of the disease. Germline testing for the BRCA2 copy number loss was unremarkable. After 6 cycles of carboplatin and etoposide in combination with androgen deprivation therapy (ADT) the Eastern Cooperative Oncology Group (ECOG) performance status has improved from 3 to 0, in addition the patient was free of pain. In line with clinical improvement, both prostate-specific membrane antigen (PSMA) and fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed a significant reduction of metastatic load. Currently, the patient is treated with ADT plus apalutamide. Conclusions: We demonstrate for the first time a case of a primary metastatic SCNC with adenocarcinoma components successfully treated by the combination of platinum-based chemotherapy plus hormonal therapy. In addition, we provide a literature overview on management of SCNC as there is no standard treatment established for this disease.
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INTRODUCTION: Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel), thus changing treatment strategies in metastatic hormonesensitive prostate cancer (mHSPC). PATIENTS AND METHODS: We conducted the first real-world analysis comprising 97 mHSPC patients from 16 Austrian medical centers, among them 79.4% of patients received abiraterone and 17.5% darolutamide treatment. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney U test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). RESULTS: Of 83.5% patients with synchronous and 16.5% with metachronous disease were included. 83.5% had high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37%, and 24.3% of patients, respectively. Importantly, a nonsimultaneous onset of chemotherapy and ARPI, performed in 44.3% of patients, was associated with significantly worse treatment response (P = .015, HR 0.245). Starting ARPI before chemotherapy was associated with significantly higher probability for progression (P = .023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3 to 5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. CONCLUSIONS: Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should be administered simultaneously, however if not possible, chemotherapy should be started first.
