Prevention of bone metastases

External-beam radiation therapy (EBRT).

Bone-seeking radionuclides (strontium chloride Sr 89 [89Sr]).

Denosumab (a monoclonal antibody that inhibits osteoclast function).

Pain medication.

Corticosteroids.

Bisphosphonates.

EBRT can be very useful for palliation of bone pain. A single fraction of 8 Gy has been shown to have similar benefits on bone pain relief and QOL as multiple fractions (3 Gy × 10), as in the RTOG-9714 trial (NCT00003162).[52,53][Level of evidence A3]

A multicenter randomized trial of a single IV dose of 89Sr (150 MBq: 4 mCi) versus palliative EBRT was done in men with painful bone metastases from prostate cancer despite hormone treatment.[55][Level of evidence A1]; [56]

A multicenter randomized trial of a single IV dose of 89Sr (150 MBq: 4 mCi) versus palliative EBRT was done in men with painful bone metastases from prostate cancer despite hormone treatment.[55][Level of evidence A1]; [56]

Similar subjective pain response rates were shown in both groups: 34.7% for 89Sr versus 33.3% for EBRT alone.

A multicenter randomized trial of a single IV dose of 89Sr (150 MBq: 4 mCi) versus palliative EBRT was done in men with painful bone metastases from prostate cancer despite hormone treatment.[55][Level of evidence A1]; [56]

OS was better in the EBRT group than in the 89Sr group (P = .046; median survival, 11.0 months vs. 7.2 months).

A multicenter randomized trial of a single IV dose of 89Sr (150 MBq: 4 mCi) versus palliative EBRT was done in men with painful bone metastases from prostate cancer despite hormone treatment.[55][Level of evidence A1]; [56]

No statistically significant differences in time to subjective progression or in PFS were seen.

A multicenter randomized trial of a single IV dose of 89Sr (150 MBq: 4 mCi) versus palliative EBRT was done in men with painful bone metastases from prostate cancer despite hormone treatment.[55][Level of evidence A1]; [56]

When used as an adjunct to EBRT, 89Sr was shown to slow disease progression and to reduce analgesic requirements, compared with EBRT alone.

A placebo-controlled randomized trial (NCT00321620) compared denosumab with zoledronic acid for the prevention of skeletal events (pathological fractures, spinal cord compression, or the need for palliative bone radiation or surgery) in men with hormonal therapy-resistant prostate cancer with at least one bone metastasis.[47]

A placebo-controlled randomized trial (NCT00321620) compared denosumab with zoledronic acid for the prevention of skeletal events (pathological fractures, spinal cord compression, or the need for palliative bone radiation or surgery) in men with hormonal therapy-resistant prostate cancer with at least one bone metastasis.[47]

The median time to first on-study skeletal event was 20.7 months in the denosumab group and 17.1 months in the zoledronic acid group (HR, 0.82; 95% CI, 0.71–0.95).

A placebo-controlled randomized trial (NCT00321620) compared denosumab with zoledronic acid for the prevention of skeletal events (pathological fractures, spinal cord compression, or the need for palliative bone radiation or surgery) in men with hormonal therapy-resistant prostate cancer with at least one bone metastasis.[47]

Serious adverse events were reported in 63% of patients who received denosumab versus 60% in patients who received zoledronic acid. The cumulative incidence of osteonecrosis of the jaw was low in both study arms (2% in the denosumab arm vs. 1% in the zoledronic acid arm). There was grade 3 to 4 toxicity and no difference in survival. The incidence of hypocalcemia was higher in the denosumab arm (13% vs. 6%).[57]

A randomized placebo-controlled trial included 1,432 men with castration-resistant prostate cancer with no evidence of any metastases. Patients were given denosumab (120 mg administered subcutaneously every 4 weeks) to prevent the first evidence of bone metastasis (whether symptomatic or not).[57][Level of evidence B1]

A randomized placebo-controlled trial included 1,432 men with castration-resistant prostate cancer with no evidence of any metastases. Patients were given denosumab (120 mg administered subcutaneously every 4 weeks) to prevent the first evidence of bone metastasis (whether symptomatic or not).[57][Level of evidence B1]

After a median follow-up of 20 months, median bone metastasis-free survival was 29.5 versus 25.2 months in the denosumab versus placebo arms (HR, 0.85; 95% CI, 0.73–0.98; P = .028).

A randomized placebo-controlled trial included 1,432 men with castration-resistant prostate cancer with no evidence of any metastases. Patients were given denosumab (120 mg administered subcutaneously every 4 weeks) to prevent the first evidence of bone metastasis (whether symptomatic or not).[57][Level of evidence B1]

Symptomatic bone metastases were reported in 69 (10%) denosumab patients versus 96 (13%) placebo patients (HR, 0.67; 95% CI, 0.49–0.92; P = .01).

A randomized placebo-controlled trial included 1,432 men with castration-resistant prostate cancer with no evidence of any metastases. Patients were given denosumab (120 mg administered subcutaneously every 4 weeks) to prevent the first evidence of bone metastasis (whether symptomatic or not).[57][Level of evidence B1]

There were no differences in OS between the two groups.

A randomized placebo-controlled trial included 1,432 men with castration-resistant prostate cancer with no evidence of any metastases. Patients were given denosumab (120 mg administered subcutaneously every 4 weeks) to prevent the first evidence of bone metastasis (whether symptomatic or not).[57][Level of evidence B1]

Osteonecrosis occurred in 33 (5%) of men on the denosumab arm versus none on the placebo arm. Hypocalcemia occurred in 12 (2%) versus 2 (<1%) men, and urinary retention in 54 (8%) of men on denosumab versus 31 (4%) of men on placebo.