Extrapulmonary neuroendocrine carcinoma: the decisions you may face
5 treatment settings, 5 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Diagnosis and staging
Biopsy with Ki-67, morphology and p53 or Rb immunohistochemistry to separate carcinoma from grade 3 tumour; FDG PET and CT; somatostatin receptor PET only if radioligand therapy is contemplated.
A scan that shows where a radioactive tracer accumulates, so it images what tumours are doing rather than what they look like.
- Whole-body biology in one scan
- Quantitative
- Any target with a ligand can in principle be imaged
A CT scan is a fast 3D X-ray that shows the size and shape of tumours and whether they have spread.
- Fast, ubiquitous
- Sub-millimetre resolution
- Standard for RECIST response
A PET scan using a radioactive hormone mimic that lights up neuroendocrine tumours and shows whether the matching radioactive treatment will work.
- Whole-body receptor map
- Theranostic gatekeeper for 177Lu-DOTATATE
- Changes management in ~40% of patients versus conventional imaging
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Resolution ~4 mm
- Tracer supply and cost
- Inflammation confounds FDG
- Anatomic only; cannot distinguish scar from live tumour
- Radiation dose
- Poor for brain, marrow, and small peritoneal disease
- Physiologic uptake in pancreas uncinate, spleen, pituitary
- Poor sensitivity in SSTR-negative high-grade disease
- 68Ga generator supply and short half-life
- Between PET (positron emission tomography), CT (computed tomography) and Somatostatin receptor PET (68Ga/64Cu-DOTATATE), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Neuroendocrine and Adrenal Tumors), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (diagnosis and staging), which of the standard options do you recommend and why?Why: Guideline options include: Biopsy with Ki-67, morphology and p53 or Rb immunohistochemistry to separate carcinoma from grade 3 tumour; FDG PET and CT; somatostatin receptor PET only if radioligand therapy is contemplated.
Add these to your appointment list, or take the full question set for this cancer.
Localised disease
Resection or definitive chemoradiotherapy with perioperative platinum-etoposide, following the limited-stage small-cell lung cancer model.
Platinum plus etoposide has been the chemotherapy backbone of small-cell lung cancer for over 40 years, and is now given with immunotherapy.
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Reduce to 75% for CrCl 15-50.
- Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Dose by Calvert formula using GFR (see the calculators).
- Between Platinum + etoposide (EP / CE), Etoposide, Cisplatin and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Neuroendocrine and Adrenal Tumors), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (localised disease), which of the standard options do you recommend and why?Why: Guideline options include: Resection or definitive chemoradiotherapy with perioperative platinum-etoposide, following the limited-stage small-cell lung cancer model.
- Am I a candidate for Platinum + etoposide (EP / CE), Etoposide, Cisplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Metastatic, first line
Platinum with etoposide (cisplatin or carboplatin), with a PD-1 or PD-L1 antibody added by extrapolation from small-cell lung cancer or within a trial.
Platinum plus etoposide has been the chemotherapy backbone of small-cell lung cancer for over 40 years, and is now given with immunotherapy.
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.
A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.
A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Reduce to 75% for CrCl 15-50.
- Dose by Calvert formula using GFR (see the calculators).
- Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (immune-mediated) · Monotherapy pooled | 3% | 0.8% |
| Hepatitis (immune-mediated) · Monotherapy pooled | 1.8% | 0.7% |
| Colitis (immune-mediated) · Monotherapy pooled | 1% | 0.5% |
| Hypothyroidism (immune-mediated) · Monotherapy pooled | 4.9% | 0.2% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal | 18.3% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Platinum + etoposide (EP / CE), Etoposide, Carboplatin and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Atezolizumab or Durvalumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Neuroendocrine and Adrenal Tumors), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (metastatic, first line), which of the standard options do you recommend and why?Why: Guideline options include: Platinum with etoposide (cisplatin or carboplatin), with a PD-1 or PD-L1 antibody added by extrapolation from small-cell lung cancer or within a trial.
- Am I a candidate for Platinum + etoposide (EP / CE), Etoposide, Carboplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Second line
FOLFIRI, FOLFOX, capecitabine-temozolomide or topotecan; nivolumab with ipilimumab in selected patients (DART); DLL3-directed T-cell engagers in trials.
FOLFIRI is the other backbone bowel-cancer chemotherapy, swapping oxaliplatin for irinotecan. Used first or second line and, since 2026, with the BRAF combination.
FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.
CAPTEM (capecitabine plus temozolomide) is an all-oral chemotherapy pair that shrinks pancreatic neuroendocrine tumours in about a third of patients.
Topotecan is the long-standing second-line chemotherapy for relapsed small-cell lung cancer, and now the comparator that new drugs must beat.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
- Tests Nivolumab, IpilimumabMore than 50 cohorts of rare solid tumours with no standard therapy: nivolumab plus ipilimumab in a single-arm basket run across the NCI's community network
Neuroendocrine cohort: about one in four responded, concentrated in high-grade disease; angiosarcoma cohort about one in four, mostly cutaneous scalp and face tumours; many other cohorts inactive.
- DAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard ChemotherapyPhase 3NCT07544654390 peopleevidence 48A Phase III, Multi-center, Open-label, Randomised, Controlled Trial of Intravenous Obrixtamig in Combination With Carboplatin and Etoposide vs. Carboplatin and Etoposide as First-line Therapy in DLL3-positive Patients With Unresectable Locally Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas
No headline result recorded yet.
- DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine CancersPhase 2NCT05882058204 peopleevidence 27DAREON™-5: An Open-label, Multi-center Phase II Dose Selection Trial of Intravenous BI 764532, a DLL3-targeting T Cell Engager, in Patients With Relapsed/Refractory Extensive-stage Small Cell Lung Cancer and in Patients With Other Relapsed/Refractory Neuroendocrine Carcinomas
No headline result recorded yet.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between FOLFIRI (5-FU, leucovorin, irinotecan), FOLFOX (5-FU, leucovorin, oxaliplatin), Capecitabine + temozolomide (CAPTEM) and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in DART (SWOG S1609): nivolumab plus ipilimumab in rare tumours and DAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard Chemotherapy, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Nivolumab or Ipilimumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Neuroendocrine and Adrenal Tumors), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (second line), which of the standard options do you recommend and why?Why: Guideline options include: FOLFIRI, FOLFOX, capecitabine-temozolomide or topotecan; nivolumab with ipilimumab in selected patients (DART); DLL3-directed T-cell engagers in trials.
- Am I a candidate for FOLFIRI (5-FU, leucovorin, irinotecan), FOLFOX (5-FU, leucovorin, oxaliplatin), Capecitabine + temozolomide (CAPTEM) or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DART (SWOG S1609): nivolumab plus ipilimumab in rare tumours and DAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard Chemotherapy apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Ki-67 near 20 to 55 percent with well-differentiated features
Reclassify as grade 3 neuroendocrine tumour and treat accordingly.
CAPTEM (capecitabine plus temozolomide) is an all-oral chemotherapy pair that shrinks pancreatic neuroendocrine tumours in about a third of patients.
Lutetium-177 dotatate was the first modern radioligand therapy (2018), for neuroendocrine tumours, and is now used in first line.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Lymphopenia · NETTER-1; grade 3-4 rates | - | 44% |
| GGT increased · NETTER-1; grade 3-4 rates | - | 20% |
| Vomiting · NETTER-1; grade 3-4 rates | - | 7% |
| Nausea · NETTER-1; grade 3-4 rates | - | 5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Capecitabine + temozolomide (CAPTEM) and Lutetium-177 dotatate, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Lutetium-177 dotatate are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Neuroendocrine and Adrenal Tumors), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (ki-67 near 20 to 55 percent with well-differentiated features), which of the standard options do you recommend and why?Why: Guideline options include: Reclassify as grade 3 neuroendocrine tumour and treat accordingly.
- Am I a candidate for Capecitabine + temozolomide (CAPTEM), Lutetium-177 dotatate, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.