Treatment of Small Cell Neuroendocrine Prostate Cancer with Visceral Metastases
This patient requires immediate transition to platinum-based cytotoxic chemotherapy (cisplatin/etoposide or carboplatin/etoposide) and discontinuation of leuprolide, as small cell/neuroendocrine prostate cancer does not respond to androgen deprivation therapy. 1
Understanding the Clinical Scenario
This represents treatment-emergent small cell/neuroendocrine transformation of prostate cancer, which occurs in approximately 17% of patients with metastatic castration-resistant prostate cancer (mCRPC). 1 This aggressive histologic variant is characterized by:
- Low PSA levels despite large metastatic burden and visceral disease (liver metastasis in this case) 1
- Resistance to androgen deprivation therapy - these tumors no longer respond to hormonal manipulation 1
- Significantly worse prognosis compared to adenocarcinoma, with hazard ratio of 2.02 for overall survival 1
- Behavior similar to small cell lung cancer rather than typical prostate adenocarcinoma 1
Immediate Treatment Algorithm
Step 1: Discontinue Current Therapy
- Stop leuprolide - androgen deprivation provides no benefit for small cell/neuroendocrine histology 1
- Discontinue axitinib - this VEGF inhibitor is not indicated for small cell carcinoma 1
Step 2: Initiate Platinum-Based Chemotherapy
First-line regimen options (choose one): 1
- Cisplatin 60-80 mg/m² IV day 1 + etoposide 80-100 mg/m² IV days 1-3, every 21 days
- Carboplatin AUC 5-6 IV day 1 + etoposide 80-100 mg/m² IV days 1-3, every 21 days (preferred if renal impairment or neuropathy concerns)
- Docetaxel 75 mg/m² + carboplatin AUC 5-6 every 21 days
- Cabazitaxel 25 mg/m² + carboplatin AUC 4-5 every 21 days
Carboplatin/etoposide is generally preferred over cisplatin/etoposide in elderly patients due to better tolerability, less nephrotoxicity, and no requirement for aggressive hydration. 1
Step 3: Consult NCCN Small Cell Lung Cancer Guidelines
The NCCN explicitly recommends consulting their Small Cell Lung Cancer guidelines for additional first-line and subsequent therapy options, as the biology and treatment response patterns are nearly identical. 1
Critical Prognostic Factors
This patient faces particularly poor prognosis due to: 1
- Visceral (liver) metastases present
- Prior exposure to androgen pathway inhibition (leuprolide)
- Small cell histology with HR 2.02 for death compared to adenocarcinoma
- Genomic analysis shows DNA repair mutations and small cell histology are almost mutually exclusive, limiting targeted therapy options 1
Monitoring During Chemotherapy
- PSA is unreliable for monitoring response in small cell/neuroendocrine prostate cancer due to characteristically low levels despite high tumor burden 1
- Use CT imaging of chest/abdomen/pelvis every 2-3 cycles to assess response by RECIST 1.1 criteria 1
- Monitor liver function closely given hepatic metastasis - assess AST, ALT, bilirubin, alkaline phosphatase before each cycle 1
- Complete blood counts before each cycle to assess for myelosuppression 1
- Neuron-specific enolase (NSE) and chromogranin A may serve as tumor markers if elevated at baseline 2
Common Pitfalls to Avoid
Do not continue androgen deprivation therapy - this is ineffective for small cell/neuroendocrine histology and delays appropriate cytotoxic treatment. 1
Do not use radium-223 - this is contraindicated in patients with visceral metastases. 1
Do not rely on PSA for disease monitoring - small cell carcinoma characteristically has low PSA despite extensive disease burden. 1
Do not use abiraterone or enzalutamide - these androgen pathway inhibitors are ineffective for small cell/neuroendocrine transformation. 1
Do not delay biopsy confirmation - the NCCN specifically recommends biopsy of accessible metastatic lesions to identify small cell/neuroendocrine features in patients with mCRPC, particularly those with visceral disease and low PSA. 1
Second-Line Options After Progression
If disease progresses on first-line platinum/etoposide chemotherapy: