Neuroendocrine Cervical Cancer Treatment
For neuroendocrine cervical cancer, treatment should be multimodal combining surgery with chemotherapy (using cisplatin/etoposide regimens adapted from small cell lung cancer protocols) for early-stage resectable disease, definitive chemoradiotherapy for locoregionally advanced unresectable disease, and platinum-based chemotherapy for metastatic disease. 1
Treatment Approach by Stage
Early-Stage Resectable Disease (FIGO I-IIA)
- Perform radical hysterectomy with lymph node dissection (RH+LND) as the primary surgical approach, which demonstrates significantly better disease-free survival (P=0.015) and overall survival (P=0.006) compared to less extensive surgery 2
- Add bilateral salpingo-oophorectomy (BSOE) to the surgical procedure, as this is associated with improved overall survival (P=0.023) 2
- Administer adjuvant chemotherapy with cisplatin/carboplatin and etoposide (EP) following surgery, as this is the most commonly used and evidence-supported regimen 3, 1
- Consider paclitaxel-platinum (TP/C) regimens as an alternative, particularly for tumors >4 cm in diameter (P=0.0005), though this requires further validation 2
- Incorporate radiotherapy or chemoradiotherapy into the treatment plan, as combined modality therapy improves outcomes 1, 4
Locoregionally Advanced Unresectable Disease
- Deliver definitive chemoradiotherapy as the primary treatment modality 1
- Use platinum-based chemotherapy regimens (cisplatin/etoposide) concurrently with radiation 1, 3
- Follow the same chemotherapy protocols used for small cell lung cancer given the histologic similarities 1
Metastatic or Recurrent Disease
- Administer palliative chemotherapy with cisplatin and etoposide as first-line treatment 1, 3
- Consider topotecan, paclitaxel, and bevacizumab as alternative regimens for recurrent disease 3
- Evaluate for immune checkpoint inhibitor therapy with ipilimumab and nivolumab combination, which has demonstrated durable responses in recurrent neuroendocrine cervical carcinoma 5, 3
Critical Diagnostic Considerations
- Confirm diagnosis with immunohistochemical staining for synaptophysin (79% positive), CD56 (61% positive), chromogranin (66% positive), and neuron-specific enolase (69% positive) 3
- Recognize that small cell neuroendocrine carcinoma represents 80.4% of cases, large cell 12.0%, and other subtypes 7.6% 3
- Note the strong association with HPV 18 (and to a lesser extent HPV 16) in high-grade neuroendocrine cervical cancer 6
Prognostic Factors and Risk Stratification
- Identify high-risk features including tumor diameter >4 cm, lymph node metastasis (LNM), deep stromal invasion (DSI), and lymphovascular space invasion (LVSI), all of which significantly worsen disease-free and overall survival 2
- Understand that early lymphatic node invasion occurs in 68% and vessel invasion in 90% of cases, explaining the aggressive behavior 4
- Recognize the poor overall prognosis with mean recurrence-free survival of 16 months and mean overall survival of 40 months across all stages 3
- Note that median survival is only 21-22 months compared to 10 years for squamous cell carcinoma 6
Common Pitfalls to Avoid
- Do not treat neuroendocrine cervical cancer with standard cervical cancer protocols alone—the aggressive biology demands more intensive multimodal therapy adapted from small cell lung cancer approaches 1, 3
- Do not omit adjuvant chemotherapy after surgery even in early-stage disease, as nearly half of Stage I-II patients will recur without systemic therapy 4
- Do not delay treatment given the tendency for early nodal and hematogenous spread 6
- Be aware that despite optimal multimodal therapy, recurrence rates remain high, with approximately 50% of early-stage patients experiencing disease recurrence 4