From the Guidelines
The most effective treatment for neuroendocrine prostate cancer (NEPC) typically involves platinum-based chemotherapy regimens, particularly cisplatin or carboplatin combined with etoposide, as recommended by the NCCN guidelines 1.
Treatment Approach
The treatment of NEPC is challenging due to its aggressive nature and lack of response to traditional androgen deprivation therapy (ADT) or androgen receptor pathway inhibitors like enzalutamide or abiraterone.
- NEPC lacks androgen receptor expression, making it unresponsive to hormone therapies.
- The platinum-based approach is borrowed from small cell lung cancer treatment protocols due to similar neuroendocrine features.
- A common regimen is cisplatin 75 mg/m² on day 1 with etoposide 100 mg/m² on days 1-3, repeated every 21 days for 4-6 cycles.
- Alternatively, carboplatin (AUC 5) can be substituted for cisplatin in patients with renal impairment or other contraindications.
Monitoring and Considerations
- Regular monitoring with imaging every 2-3 cycles and neuroendocrine markers (chromogranin A, neuron-specific enolase) is essential to assess treatment response.
- Clinical trials should be strongly considered when available, as standard treatments have limited durability.
- For patients with limited metastatic disease, consolidative radiation therapy to residual sites may be considered.
- The NCCN guidelines recommend considering small cell/neuroendocrine carcinoma of the prostate in patients with disease that no longer responds to ADT and who test positive for metastases 1.
- Genomic analysis has shown that DNA repair mutations and small cell/neuroendocrine histology are almost mutually exclusive, highlighting the importance of biopsy and molecular characterization in guiding treatment decisions 1.
From the Research
Treatment Options for Neuroendocrine Prostate Cancer
- Platinum-based chemotherapy is a commonly used treatment for neuroendocrine prostate cancer (NEPC), with a reported objective response rate of 66.7% and disease control rate of 91.7% 2.
- The combination of carboplatin and etoposide has been shown to be effective in metastatic castration-resistant prostate cancer, with a median progression-free survival of 3.3 months and median overall survival of 8.1 months 3.
- Multidisciplinary therapy using systemic and local chemotherapy and radiation therapy may be a promising option for improving survival in patients with NEPC, with one reported case of a patient surviving for 24 months after initiation of second-line chemotherapy 4.
- Somatostatin receptor scintigraphy (SRS) findings and the presence of liver metastases may be prognostic predictors of NEPC, with SRS-positive patients having a median overall survival of 31.6 months and liver metastasis-negative patients having a median overall survival of 31.6 months 2.
- Immunotherapy with pembrolizumab may be a potential treatment option for patients with NEPC, particularly those with high tumor mutational burden, as reported in a case study 5.
Challenges in Treating Neuroendocrine Prostate Cancer
- NEPC is a rare and aggressive disease with a poor prognosis, and there is currently no established standard therapy 6, 2.
- The clinical course and treatment outcomes of NEPC are unclear, and more research is needed to understand the disease and develop effective treatments 2.
- The duration of response to platinum-based chemotherapy is often not sufficient, and new treatment options are needed to improve outcomes for patients with NEPC 2.