This patient falls into the category of having high-volume disease. Pain was not a criterion for eligibility in CHAARTED. I would offer this man ADT and 6 cycles of docetaxel. Hormonal therapy is probably the most effective bone-targeted treatment that this patient needs.

Similar to my approach for the patient who had extensive bone and liver metastases, I would offer either goserelin/bicalutamide with docetaxel for 6 cycles or combined androgen blockade alone. Again, I would also discuss the possibility of using radiation therapy. I would not use bisphosphonates or denosumab at this juncture. I do believe that we should begin to consider the early use of radium-223.

This patient would qualify for ADT with docetaxel. I would not administer a RANK-ligand inhibitor or a bisphosphonate at this time. The rationale is 2-fold: First, all the safety data we have for zoledronic acid or denosumab are restricted to 2 years of treatment. When these agents are administered for a longer period we have increasingly observed complications, such as osteonecrosis of the jaw. So these treatments should not be started too early. In the Netherlands we conducted a study in which patients with castration-resistant metastatic prostate cancer were randomly assigned to receive chemotherapy with or without the third-generation bisphosphonate risedronate. The outcome was exactly the same. No improvement occurred in radiologic progression-free survival and no improvement in skeletal-related complications. So, what would be the role of bisphosphonates or denosumab for patients who are already receiving active anti-tumor treatment?

For this patient I would first want to check testosterone levels. A 62-year-old patient with extensive bony metastases but only minimal complaints of pain may be a good candidate for initial therapy with an LHRH antagonist and then a flip over to an LHRH agonist. This is a patient for whom I would consider adding in docetaxel, and of course the risks and benefits of adding chemotherapy should be discussed with his medical oncologist.

The use of a bisphosphonate or denosumab would also be reasonable in this setting. At our center we prefer denosumab. I believe that the evidence supports the use of bone-targeted therapy in patients with extensive bone disease.

Such a patient would qualify as having high-volume disease according to the CHAARTED trial criteria. I have no question about administering ADT, but I would have a discussion with him about the data from CHAARTED. A patient with these characteristics should easily be able to tolerate 6 cycles of docetaxel, and I would definitely also use the bone-targeted agent denosumab in this situation.

I would approach this case according to the CHAARTED protocol. I would not use any prophylactic bone-targeted agents because I am not convinced that the ratio of benefit to risk in this particular scenario is in favor of such an approach.

Standard androgen deprivation is still the mainstay of all metastatic disease, but this patient would also fit the CHAARTED criteria, and as I mentioned previously, that’s now a standard as first-line therapy for a man with extensive bony metastasis, whether it’s asymptomatic or not.

Again, I would not offer any bone-targeted treatment until his response to chemotherapy and androgen deprivation was assessed.

I would recommend ADT and docetaxel for this 62-year-old patient. I would not offer this patient any bone-targeted treatment, even though he has extensive bony metastases.

My choice of therapy for this patient would be ADT and docetaxel. I would not recommend bone-targeted therapy because we have no data to support its use.

This patient would be ideally suited for ADT in combination with docetaxel. In terms of bone-targeted therapy, I believe that neither zoledronic acid nor denosumab has been validated in this setting. Although my inclination is to administer bone-targeted agents to these patients, the agents have not to my knowledge been studied in the androgen-sensitive population. Our preference is for denosumab because of its ease of administration and lack of requirement for monitoring renal function. I am a co-author of Study 103, which showed not only noninferiority but also superiority in delay of skeletal-related events with denosumab versus zoledronic acid for men with castration-resistant prostate cancer.