Management of Neuroendocrine Tumor with Ki67 of 80%
A neuroendocrine tumor with a Ki67 proliferation index of 80% should be treated with platinum-based chemotherapy (cisplatin or carboplatin with etoposide) as first-line therapy. 1
Classification and Grading
With a Ki67 of 80%, this tumor is classified as:
- Neuroendocrine carcinoma (NEC G3)
- Poorly differentiated
- High-grade
The WHO classification system for neuroendocrine neoplasms uses Ki67 as a critical grading parameter:
- G1: Ki67 ≤2%
- G2: Ki67 3-20%
- G3: Ki67 >20% 1
At 80%, this tumor falls well above the G3 threshold and represents a highly aggressive neoplasm.
Treatment Approach
First-line Treatment
- Platinum-based chemotherapy: Cisplatin or carboplatin with etoposide is the recommended standard first-line chemotherapy for NEC G3 1
- This is considered an absolute indication with strong evidence (Level III, A recommendation)
- Surgery is contraindicated as an upfront approach in high-grade NEC G3 1
Response and Prognosis
- Patients with Ki67 >55% have significantly poorer outcomes:
- Median progression-free survival (mPFS) of only 4-6 months 1
- Much more aggressive course than lower-grade NETs
- High likelihood of rapid progression
Second-line Options
If progression occurs after platinum-based therapy, consider:
- FOLFIRI (5-FU/leucovorin/irinotecan)
- FOLFOX (5-FU/leucovorin/oxaliplatin)
- CAPTEM (capecitabine and temozolomide)
- Bevacizumab 1
Important Considerations
Peptide Receptor Radionuclide Therapy (PRRT)
- PRRT is generally not recommended for NECs with Ki67 >55% 1
- Studies show significantly worse outcomes in high Ki67 tumors
- Clinical trials (like NETTER-2) are investigating this further
Targeted Therapies
- Everolimus and sunitinib are not recommended in NEC G3 outside of clinical trials 1
Monitoring and Follow-up
- Regular imaging to assess treatment response
- Expect rapid progression without treatment
- Consider clinical trials when available
Pitfalls to Avoid
Misclassification: Ensure accurate Ki67 assessment as it dramatically impacts treatment decisions. Digital image analysis or manual counting of >2000 cells is more reliable than eyeball estimation 2, 3
Delayed treatment: Given the aggressive nature of high-grade NECs, prompt initiation of platinum-based chemotherapy is essential
Inappropriate use of treatments for lower-grade NETs: Treatments effective for G1/G2 NETs (like somatostatin analogs) are not appropriate for high-grade NECs with Ki67 of 80%
Upfront surgical approach: Surgery as initial treatment is contraindicated in NEC G3 1
In summary, a neuroendocrine tumor with Ki67 of 80% represents a high-grade neuroendocrine carcinoma requiring immediate treatment with platinum-based chemotherapy. The prognosis is poor compared to lower-grade NETs, and treatment should focus on systemic chemotherapy rather than surgical or targeted approaches used for well-differentiated NETs.