Bone metastases in advanced prostate cancer. Management

6/20/22, 12:19 AM 17128
significant differences were noted in either overall survival or clinical progression-free
survival in the intent-to-treat analysis.
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Two small randomized phase III trials compared samarium-153 with placebo. Both found
that treatment with samarium-153 was more effective than placebo in providing pain relief
[23,24].
Myelosuppression is the predominant toxicity associated with beta particle-emitting
radioisotopes and was more prominent with strontium than samarium. This toxicity has limited
their usage, and there is no evidence that beta emitting radioisotopes prolong survival, in
contrast to alpha emitting radioisotopes [4].
Bisphosphonates — Bone modifying agents such as bisphosphonates or denosumab are
indicated for men with bone metastases from castration resistant prostate cancer, whether they
are symptomatic or not. (See "Osteoclast inhibitors for patients with bone metastases from
breast, prostate, and other solid tumors", section on 'Indications for osteoclast inhibitor
therapy'.)
In addition, intravenous ibandronate or other bisphosphonates may offer some degree of
analgesia, and represent an alternative to EBRT for the management of pain due to bone
metastases in men with CRPC who are not already on an osteoclast inhibitor. However, these
agents are not approved for this indication in the United States.
Intravenous bisphosphonates can be effective for palliation of bone pain, but they are probably
not as effective as RT:
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One meta-analysis of three trials (876 participants) comparing bisphosphonates with no
bisphosphonates in men with metastatic CRPC showed no statistically significant
difference in pain response (RR 1.15, 95% CI 0.93-1.43; 3 trials; 876 participants; low quality
evidence). In absolute terms, bisphosphonates resulted in a pain response in 40 more
participants per 1000 (19 fewer to 114 more) and no clinically relevant differences in the
proportion of patients with decreased analgesic consumption (RR 1.19, 95% CI 0.87-1.63)
[25]. Higher rates of nausea, renal adverse effects, and jaw osteonecrosis were observed
with the bisphosphonates.
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IV bisphosphonates were directly compared with single-fraction RT in a multicenter trial in
which 470 men with prostate cancer and pain due to bone metastases were randomly
assigned to either one dose of intravenous ibandronate (6 mg) or RT (8 Gy) given in a
single-fraction treatment [26]. Crossover to the alternative treatment was allowed for
patients who did not have pain relief at four weeks. There was no statistically significant
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