The first 60 days: Extrapulmonary neuroendocrine carcinoma
Extrapulmonary neuroendocrine carcinoma is the fast-growing, poorly differentiated form of neuroendocrine cancer arising outside the lung, most often in the bowel, oesophagus, stomach or pancreas. It behaves like small-cell lung cancer and is treated the same way, with platinum and etoposide chemotherapy, and drugs against the DLL3 protein are now in phase 3 trials. Below, week by week, is what OnCo's record of Extrapulmonary neuroendocrine carcinoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
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.
Ask which of these were tested and what the results were; see the report reader for what each value means.
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.
- PathologistNamed in the standard of care for: Diagnosis and staging, Metastatic, first line.
- RadiologistNamed in the standard of care for: Diagnosis and staging.
- SurgeonNamed in the standard of care for: Localised disease.
- Medical oncologistNamed in the standard of care for: Diagnosis and staging, Localised disease, Metastatic, first line, Second line and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Localised disease, Ki-67 near 20 to 55 percent with well-differentiated features.
- Transplant and cell therapy teamNamed in the standard of care for: Localised disease, Metastatic, first line.
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.
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.
Resection or definitive chemoradiotherapy with perioperative platinum-etoposide, following the limited-stage small-cell lung cancer model.
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.
- 3.Ki-67 near 20 to 55 percent with well-differentiated featuresNCCN Guidelines: Neuroendocrine and Adrenal Tumors
Reclassify as grade 3 neuroendocrine tumour and treat accordingly.
FOLFIRI, FOLFOX, capecitabine-temozolomide or topotecan; nivolumab with ipilimumab in selected patients (DART); DLL3-directed T-cell engagers in trials.
FOLFIRI (5-FU, leucovorin, irinotecan)FOLFOX (5-FU, leucovorin, oxaliplatin)Capecitabine + temozolomide (CAPTEM)TopotecanNivolumabIpilimumabDART (SWOG S1609): nivolumab plus ipilimumab in rare tumoursDAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard ChemotherapyDAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine CancersDLL3
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 Ki-67 above 20 percent, usually far higher, with poorly differentiated morphology, Synaptophysin, chromogranin and INSM1 by immunohistochemistry, p53 and Rb by immunohistochemistry, FDG PET, 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 Small-cell neuroendocrine carcinomaof the gastrointestinal tract, Large-cell neuroendocrine carcinomaof the gastrointestinal tract, Colorectal NEC.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Diagnosis and staging
- For my situation (diagnosis and staging), which of the standard options do you recommend and 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.
Localised disease
- For my situation (localised disease), which of the standard options do you recommend and 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?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic, first line
- For my situation (metastatic, first line), which of the standard options do you recommend and 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?Knowing the expected toxicities helps you plan work, family, and supportive care.
Second line
- For my situation (second line), which of the standard options do you recommend and 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?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?Trial populations differ from individual patients; ask how closely you match.
Ki-67 near 20 to 55 percent with well-differentiated features
- For my situation (ki-67 near 20 to 55 percent with well-differentiated features), which of the standard options do you recommend and 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?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of DAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard Chemotherapy, DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers, A Study of Peluntamig (PT217) in Patients With Neuroendocrine Carcinomas Expressing DLL3 (the SKYBRIDGE Study), Peluntamig?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 randomised trial has improved on platinum-etoposide in first line”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether adding a PD-1 or PD-L1 antibody helps, as it does in small-cell lung cancer, is untested in a phase 3”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- DAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard ChemotherapyPhase 3 · recruiting · NCT07544654A 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
- DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine CancersPhase 2 · recruiting · NCT05882058DAREON™-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
- DART (SWOG S1609): nivolumab plus ipilimumab in rare tumoursPhase 2 · active · NCT02834013More 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
- A Study of Peluntamig (PT217) in Patients With Neuroendocrine Carcinomas Expressing DLL3 (the SKYBRIDGE Study)Phase 1/2 · recruiting · NCT05652686An Open-label, Multicenter, Dose Escalation, and Dose Expansion Phase 1/2 Study With Peluntamig (PT217) Followed by a Key ChemotherapY and/or Checkpoint Inhibitor ComBination in Patients With NeuRoendocrIne Carcinomas That Are Known to be DLL3 expressinG CancErs (SKYBRIDGE)
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Extrapulmonary neuroendocrine carcinoma: the full pageExtrapulmonary neuroendocrine carcinoma is the fast-growing, poorly differentiated form of neuroendocrine cancer arising outside the lung, most often in the bowel, oesophagus, stomach or pancreas. It behaves like small-cell lung cancer and is treated the same way, with platinum and etoposide chemotherapy, and drugs against the DLL3 protein are now in phase 3 trials.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Radiotherapy: Using high-energy X-rays or particles to damage the DNA of cancer cells in a precisely aimed volume of the body.
- Tumour differentiation (well / moderately / poorly differentiated): How much the cancer cells still resemble the normal tissue they came from.
- Neuroendocrine tumour grade (Ki-67) and WHO classification: How fast the tumour cells are dividing, measured by Ki-67 staining, separates slow-growing neuroendocrine tumours from aggressive neuroendocrine carcinomas and decides the treatment.
- 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.