Prescrire international

Second-line treatment of metastatic prostate cancer. Prednisone and radiotherapy for symptom relief.

PMID 23593699


First-line treatment based on androgen suppression is initially very effective in relieving the symptoms of metastatic prostate cancer. When androgen suppression no longer controls disease progression and symptoms, which treatments are known to improve duration or quality of survival? To answer this question, we reviewed the evidence using the standard Prescrire methodology. Low doses of corticosteroids, such as prednisone 5 to 10 mg per day, appear to improve quality of life for a few months by relieving symptoms in 20% to 40% of patients. When added to prednisone, docetaxel, a cytotoxic drug, tends to be more effective than mitoxantrone in terms of pain relief and quality of life. Docetaxel prolongs survival by about 2 months but provokes severe adverse effects in one-quarter of patients. Adding estramustine to this combination prolongs survival but carries a risk of serious thromboembolic events. Addition of bevacizumab has no proven impact on survival. After failure of cytotoxic chemotherapy with docetaxel, two hormonal treatments, abiraterone and enzalutamide, appear to prolong survival by about 4 or 5 months, and are associated with moderate adverse effects. However, these results are based on only one trial of each drug. Cabazitaxel is also moderately effective in terms of survival but has a less favourable adverse effect profile than abiraterone. A meta-analysis of trials of bisphosphonates used to prevent complications of bone metastases showed no major benefit, including in terms of pain relief. Bisphosphonates are not sufficiently effective to justify exposing patients to their potentially serious adverse effects. In one trial, the harm-benefit balance of denosumab was no better than that of zoledronic acid, a bisphosphonate. External beam radiation therapy or intravenous infusion of strontium-89 (a radioisotope) each relieves pain associated with bone metastases in over 70% of cases. If metastatic prostate cancer progresses despite androgen suppression, the two main options in 2012 are either: palliative treatment with corticosteroids and external beam radiation therapy or radioisotope infusion; or docetaxel followed by abiraterone, which slightly prolongs survival but at a cost of sometimes serious adverse effects.