Following a review of the Cancer Care Ontario (CCO) guideline on bone health and bone-targeted therapies for men with prostate cancer by an American Society of Clinical Oncology (ASCO) expert panel, all original guideline recommendations were endorsed by the latter organization, and a number of discussion points were added.

Androgen-deprivation therapy (ADT)-induced bone loss, as well as the development of bone metastases, have been associated with an increased risk of skeletal-related events, and represent major threats to the bone health of men with advanced or metastatic prostate cancer.

The CCO guideline on bone health and bone-targeted therapies in men with prostate cancer was developed to facilitate the optimization of bone health in these patients throughout the disease spectrum.

Regarding patients with nonmetastatic prostate cancer at high risk of bone fracture due to treatment with ADT, the CCO guideline includes a recommendation for consideration of denosumab at the dosage indicated for osteoporosis. While the CCO guideline also includes a statement that a bisphosphonate can be used in place of denosumab when denosumab is contraindicated or unavailable, the ASCO expert panel considers oral or intravenous (IV) bisphosphonates as reasonable options for this group of patients.

Given that no bone-targeted drug has been approved for the prevention of first bone metastasis in the setting of prostate cancer, both CCO and ASCO recommend against using either bisphosphonates or denosumab at bone metastasis-indicated dosages to reduce the risk of first bone metastasis in men with nonmetastatic prostate cancer. However, these agents at these dosages are recommended to prevent or delay skeletal-related events in men with metastatic castrate-resistant prostate cancer (mCRPC).

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For men with mCRPC with symptomatic disease and bone pain, consideration of radium-223 was recommended to reduce the risk of skeletal-related events and improve quality of life. In addition, consideration of radiopharmaceuticals and IV bisphosphonates for the purpose of pain palliation was also recommended.

The CCO guideline also recommends treating men with symptomatic mCRPC characterized by predominantly bony metastases and without evidence of visceral or large nodal metastases with radium-223 as an approach for extending their survival. With respect to this recommendation, the ASCO expert panel included the qualification that radium-223 should not be administered concurrently with abiraterone and prednisone as this combination has been shown to increase the risk of bone fracture. They further stated that the evidence is insufficient for combining radium-223 with secondary therapies shown to increase survival in men with mCRPC. 

Reference

Saylor PJ, Rumble RB, Tagawa S, et al.  Bone health and bone-targeted therapies for prostate cancer: ASCO endorsement of a Cancer Care Ontario Guideline [published online January 28, 2020]. J Clin Oncol. DOI: 10.1200/JCO.19.03148