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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Neuroendocrine prostate cancer is a form that has stopped depending on the androgen receptor, either from the start or after years of hormone therapy. It no longer shows up on PSA, spreads to the liver and brain, and is treated with the platinum chemotherapy used for small-cell lung cancer.
Neuroendocrine prostate cancer includes rare de novo small-cell carcinoma and, far more often, treatment-emergent disease that arises when adenocarcinoma under prolonged androgen receptor blockade switches lineage, typically with combined loss of RB1 and TP53, PTEN loss, MYCN or AURKA amplification and loss of androgen receptor and PSA expression. It is suspected when disease progresses with a low or flat PSA, visceral or lytic bone metastases, raised chromogranin, neuron-specific enolase or lactate dehydrogenase, or FDG-avid but PSMA-negative lesions, and confirmed by biopsy showing small-cell morphology or synaptophysin and chromogranin staining. There is no approved therapy specific to it: platinum with etoposide, or carboplatin with docetaxel for mixed histology, is standard, with response rates of about half but brief duration, and androgen deprivation is usually continued. Immunotherapy adds little outside mismatch repair deficiency. DLL3 is expressed in most neuroendocrine prostate cancers, and the DLL3 T-cell engager tarlatamab, approved for small-cell lung cancer, is in trials here; EZH2 inhibitors and aurora kinase inhibitors are being tested against the lineage switch itself.
| Setting | Approach | Guideline |
|---|---|---|
| Small-cell or predominantly neuroendocrine | Cisplatin or carboplatin with etoposide, as for small-cell lung cancer; continue androgen deprivation; brain imaging. | not mapped |
| Mixed adenocarcinoma and neuroendocrine, or aggressive variant | Carboplatin plus docetaxel or cabazitaxel, then platinum with etoposide; clinical trial enrolment preferred. | not mapped |
| Recognition and biopsy | Biopsy any progression with low PSA, visceral metastases or PSMA-negative FDG-avid lesions; test for mismatch repair deficiency (pembrolizumab) and HRR genes. | not mapped |
| Trials | DLL3 T-cell engagers (tarlatamab), EZH2 inhibitors and aurora kinase inhibitors against the lineage switch; lurbinectedin borrowed from small-cell lung cancer. | not mapped |