Even among patients with metastatic hormone-refractory prostate cancer, some heterogeneity is found in prognosis and in retained hormone sensitivity. In such patients who have symptomatic bone disease, several factors are associated with worsened prognosis: poor performance status, elevated alkaline phosphatase, abnormal serum creatinine, and short (<1 year) previous response to hormonal therapy. The absolute level of PSA at the initiation of therapy in relapsed or hormone-refractory patients has not been shown to be of prognostic significance.
Some patients whose disease has progressed on combined androgen blockade can respond to a variety of second-line hormonal therapies. Aminoglutethimide, hydrocortisone, flutamide withdrawal, progesterone, ketoconazole, and combinations of these therapies have produced PSA responses in 14% to 60% of patients treated and have also produced clinical responses of 0% to 25% when assessed. The duration of these PSA responses has been in the range of 2 to 4 months. Survival rates are similar whether ketoconazole plus hydrocortisone is initiated at the same time as antiandrogen (e.g., flutamide, bicalutamide, or nilutamide) withdrawal or when PSA has risen after an initial trial of antiandrogen withdrawal as seen in the CLB-9583 trial, for example.[Level of evidence: 1iiA] Data on whether PSA changes while on chemotherapy are predictive of survival are conflicting.[19,22]
Patients treated with either luteinizing-hormone agonists or estrogens as primary therapy are generally maintained with castrate levels of testosterone. One study from ECOG showed that a superior survival resulted when patients were maintained on primary androgen deprivation; however, another study from SWOG (formerly the Southwest Oncology Group) did not show an advantage to continued androgen blockade.
Palliation for bone metastases
Painful bone metastases can be a major problem for patients with prostate cancer. Many strategies have been studied for palliation, including:[24,25,26,27,28]
- External-beam radiation therapy (EBRT).
- Bone-seeking radionuclides (strontium chloride Sr 89).
- Denosumab (a monoclonal antibody that inhibits osteoclast function).
- Pain medication.
- Gallium nitrate.
(Refer to the PDQ summary on Pain for more information.)
Evidence (palliation for bone metastases using radiation therapy):
- EBRT for palliation of bone pain can be very useful. A single fraction of 8 Gy has been shown to have similar benefits on bone pain relief and quality of life as multiple fractions (3 Gy × 10) as seen in the RTOG-9714 trial, for example.[29,30][Level of evidence: 1iiC]
Evidence (palliation for bone metastases using strontium chloride):
The use of radioisotopes such as strontium chloride Sr 89 has been shown to be effective as palliative treatment of some patients with osteoblastic metastases. As a single agent, strontium chloride Sr 89 has been reported to decrease bone pain in 80% of patients treated,
- A multicenter, randomized trial of a single intravenous dose of strontium chloride Sr 89 (150 MBq: 4 mCi) versus palliative EBRT was done in men with painful bone metastases from prostate cancer despite hormone treatment.[Level of evidence: 1iiA]; 
- Similar subjective pain response rates were shown in both groups: 34.7% for strontium chloride Sr 89 versus 33.3% for EBRT alone.
- OS was better in the EBRT group than in the strontium chloride Sr 89 group (P = .046; median survival 11.0 months vs. 7.2 months).
- No statistically significant differences in time-to-subjective progression or in progression-free survival were seen.
- When used as an adjunct to EBRT, strontium chloride Sr 89 was shown to slow disease progression and to reduce analgesic requirements, compared with EBRT alone.