The first 60 days: Neuroendocrine and small-cell prostate cancer

What happens now

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

Biomarkers your report may list

Synaptophysin, chromogranin and INSM1 staining Loss of androgen receptor and PSA expression Combined RB1 and TP53 loss MYCN and AURKA amplification DLL3 expression Serum chromogranin A, neuron-specific enolase and lactate dehydrogenase FDG PET-avid, PSMA PET-negative lesions

Ask which of these were tested and what the results were; see the report reader for what each value means.

Tests and imaging linked to this cancer

PET (positron emission tomography)PSMA PET

Weeks 1 to 3

Who is on your team

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These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.

A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.

Weeks 2 to 6

Decisions coming up

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Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.

1.Small-cell or predominantly neuroendocrine NCCN Guidelines: Prostate Cancer
Cisplatin or carboplatin with etoposide, as for small-cell lung cancer; continue androgen deprivation; brain imaging.
Platinum + etoposide (EP / CE)Cisplatin Carboplatin Etoposide Androgen deprivation & AR pathway inhibitors
2.Mixed adenocarcinoma and neuroendocrine, or aggressive variant NCCN Guidelines: Prostate Cancer
Carboplatin plus docetaxel or cabazitaxel, then platinum with etoposide; clinical trial enrolment preferred.
Carboplatin Docetaxel Cabazitaxel Cytotoxic chemotherapy
3.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.
PSMA PET PET (positron emission tomography)Pembrolizumab
4.Trials
DLL3 T-cell engagers (tarlatamab), EZH2 inhibitors and aurora kinase inhibitors against the lineage switch; lurbinectedin borrowed from small-cell lung cancer.
Tarlatamab DLL3 Mevrometostat EZH2 Lurbinectedin

Every visit

Questions to ask at each visit

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Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example Synaptophysin, chromogranin and INSM1 staining, Loss of androgen receptor and PSA expression, Combined RB1 and TP53 loss, MYCN and AURKA amplification, DLL3 expression), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include De novo small-cell carcinoma of the prostate, Treatment-emergent neuroendocrine prostate cancer, Mixed adenocarcinoma and neuroendocrine carcinoma.
Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.

Small-cell or predominantly neuroendocrine

For my situation (small-cell or predominantly neuroendocrine), which of the standard options do you recommend and why?Guideline options include: Cisplatin or carboplatin with etoposide, as for small-cell lung cancer; continue androgen deprivation; brain imaging.
Am I a candidate for Platinum + etoposide (EP / CE), Cisplatin, Carboplatin or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Mixed adenocarcinoma and neuroendocrine, or aggressive variant

For my situation (mixed adenocarcinoma and neuroendocrine, or aggressive variant), which of the standard options do you recommend and why?Guideline options include: Carboplatin plus docetaxel or cabazitaxel, then platinum with etoposide; clinical trial enrolment preferred.
Am I a candidate for Carboplatin, Docetaxel, Cabazitaxel, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Recognition and biopsy

For my situation (recognition and biopsy), which of the standard options do you recommend and why?Guideline options include: Biopsy any progression with low PSA, visceral metastases or PSMA-negative FDG-avid lesions; test for mismatch repair deficiency (pembrolizumab) and HRR genes.
Am I a candidate for Pembrolizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Trials

For my situation (trials), which of the standard options do you recommend and why?Guideline options include: DLL3 T-cell engagers (tarlatamab), EZH2 inhibitors and aurora kinase inhibitors against the lineage switch; lurbinectedin borrowed from small-cell lung cancer.
Am I a candidate for Tarlatamab, Mevrometostat, Lurbinectedin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

Are there clinical trials I could join, for example of Tarlatamab, Mevrometostat, Lurbinectedin, Ifinatamab deruxtecan?Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
I read that “No approved therapy specific to the disease; every regimen is borrowed from lung cancer”. How does that affect my plan?Open problems are where trials and second opinions matter most.
I read that “No blood test reliably detects the lineage switch before it shows on scans”. How does that affect my plan?Open problems are where trials and second opinions matter most.

From day one

Help that costs nothing

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Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

Any time

What to read next

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Words this page and the cancer page use

Neuroendocrine differentiation in prostate cancer: Prostate cancer cells that have taken on the look and the markers of nerve-and-hormone cells.
Acinar adenocarcinoma of the prostate: The ordinary type of prostate cancer, more than 95 in every 100 cases.
Castration-resistant prostate cancer (CRPC): Prostate cancer that keeps growing even though testosterone has been reduced to castrate levels.
Radiographic progression-free survival (rPFS): In cancer that has already spread, this is the time until the scans show it getting worse, or the man dies.
TNM staging for prostate cancer, and what changed in the 9th edition: The anatomical stage of prostate cancer: how far the tumour has grown (T), whether it is in the pelvic lymph nodes (N) and whether it has spread further (M).
Histologic transformation: When a lung adenocarcinoma escapes targeted therapy by turning into a different cell type, usually small-cell.

Every term links to the glossary.