Recommendations for Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
The workgroup voted unanimously to adopt the AUA guidelines (Supplementary Table 1) and made the following adaptations (Table 1):
1. The workgroup recommends that participation in clinical trials should be strongly encouraged.
2. Best supportive care and referral to palliative medicine should be recommended when appropriate.
3. There was consensus that Sipuleucel-T should not be recommended as part of local treatment practice. Sipuleucel-T is currently not licensed for use in Singapore. The Immunotherapy Prostate Adenocarcinoma Treatment (IMPACT) phase III trial reported a statistically significant 4.1-month median overall survival advantage with sipuleucel-T versus placebo (HR = 0.78; 95% CI, 0.61 to 0.98).24However, the workgroup has considered several issues that have been raised about the registration trial.25In particular, there was concern that the overall survival benefit may be a result of the detrimental effect of repeated depletion of circulating mononuclear cells in the placebo group.
4. There is lack of evidence demonstrating superiority between abiraterone and enzalutamide. In addition, the workgroup acknowledged that there are several retrospective studies indicating that either using abiraterone after enzalutamide or enzalutamide after abiraterone in castrate-resistant disease has limited activity. The workgroup accepts that there is insuffi cient data for specific recommendations on the sequencing of hormonal therapy.
5. The workgroup acknowledges that there is lack of definitive phase III trial data showing benefit of ketoconazole, although PSA responses have been observed. Clinicians may continue to recommend the use of ketoconazole on the basis of lower cost.
6. Docetaxel chemotherapy is the first-line chemotherapy of choice. The workgroup acknowledged that a lower dose (less than 75 mg/m2 every 3 weeks) may have a better toxicity profile with comparable efficacy based on the Singapore study. When starting at a lower dose of docetaxel, clinicians should consider dose escalation up to 75 nmg/m2 in the absence of significant toxicity with the lower dose.
7. Based on the results of the ALSYMPCA study, the workgroup agreed that radium-223 may be used for the treatment of castrate-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. However, the agent is not recommended if the patient is concurrently receiving chemotherapy. Clinicians should follow instructions in the Food and Drug Administration (FDA) label on haematologic evaluation before each injection.
8. The workgroup agreed that specific recommendations for castrate-sensitive prostate cancer, and bone metastases and bone health be deferred to subsequent editions of the guidelines.