Treatment Approach for Neuroendocrine Carcinoma
The treatment of neuroendocrine carcinoma should follow small cell lung cancer regimens, with combination chemotherapy using platinum agents (cisplatin or carboplatin) plus etoposide as the standard first-line approach for poorly differentiated neuroendocrine carcinomas. 1
Classification and Diagnosis
Neuroendocrine carcinomas (NECs) are classified based on their degree of differentiation:
- Well-differentiated (NET G1: Ki67 <3%)
- Moderately differentiated (NET G2: Ki67 3-20%)
- Well-differentiated high-grade (NET G3: Ki67 >20%)
- Poorly differentiated neuroendocrine carcinoma (NEC)
Diagnostic workup should include:
- Chromogranin A (CgA) and 5-HIAA as baseline tests 2
- Contrast CT scan as the diagnostic gold standard 1
- Somatostatin receptor imaging to visualize primary tumors and detect metastases 1, 2
- Pathological examination for correct classification 1
Treatment Algorithm for Neuroendocrine Carcinoma
1. Poorly Differentiated NEC (High-Grade)
First-line therapy: Platinum-based chemotherapy (cisplatin or carboplatin) plus etoposide 1
For elderly or poor-risk patients: Carboplatin plus etoposide is preferred due to equivalent efficacy with better tolerability 1
For second or third-line treatment: Cisplatin and etoposide can produce significant responses even in previously treated patients with rapidly progressing neuroendocrine tumors 1
Alternative options: Temozolomide has shown clinical benefit and can be considered, particularly for pancreatic NECs 1
2. Resectable Disease
- Surgery should be offered to patients who are fit and have limited disease (primary tumor with regional lymph nodes) 1, 2
- Surgery should be considered in those with potentially resectable liver metastases 1, 2
- Consider neoadjuvant therapy with PRRNT (Peptide Receptor Radionuclide Therapy) in selected cases to render tumors accessible to surgery 1
3. Unresectable/Metastatic Disease
For pancreatic NETs:
- Sunitinib is indicated for progressive, well-differentiated pancreatic NETs in patients with unresectable locally advanced or metastatic disease 3
- Everolimus is recommended for advanced pancreatic NETs that are progressive and well-differentiated 2
For all NETs with metastases:
- Locoregional approaches (TACE, TAE, RFA) for liver metastases 1, 2
- Somatostatin analogs for controlling hormonal syndromes and as first-line antiproliferative treatment in low-grade tumors 1, 2
- PRRT with [177Lu]Lu-DOTA-TATE for tumors with high somatostatin receptor uptake 2
- External beam radiotherapy for bone metastases 1, 2
Monitoring and Follow-up
- Monitor liver function tests at baseline and during each treatment cycle due to risk of hepatotoxicity 3
- Evaluate cardiac function, particularly in patients receiving cardiotoxic therapies 2
- Follow-up evaluations should be performed every 3 months during active treatment 2
- Imaging (CT or MRI) should be performed every 6 months 2
Key Considerations and Pitfalls
- Hepatotoxicity: Monitor liver function tests regularly as chemotherapy and targeted therapies can cause severe, sometimes fatal liver damage 3
- Cardiovascular events: Monitor for signs of heart failure, particularly with sunitinib which can cause decreased LVEF 3
- Tumor heterogeneity: NECs vary widely in behavior and response to treatment; treatment should be based on tumor grade, differentiation, and primary site 2, 4
- Delayed diagnosis: NECs often present with vague symptoms leading to late diagnosis and treatment; maintain high clinical suspicion 2
- Treatment sequencing: Limited head-to-head data exists to guide optimal treatment sequencing; consider disease factors (tumor origin, volume) and patient factors (comorbidities) 5
The treatment landscape for neuroendocrine carcinomas continues to evolve, with emerging precision medicine approaches showing promise, particularly in radiotheragnostics 6. However, the current standard of care for poorly differentiated NECs remains platinum-based chemotherapy, with consideration of surgical approaches when feasible.