Managing Pain and Treating Bone Metastases in Prostate Cancer


The ALSYMPCA phase III clinical trial, recently published, demonstrated that radium-223 dichloride was well-tolerated and resulted in an improvement in overall survival by 3.6 months compared with placebo.

When prostate cancer metastasizes, bone is one of the most common tissue types colonized by the advanced prostate cancer. An estimated 70% of men with advanced prostate cancer have detectable bone metastases, and as many as 30,000 men will die of their prostate cancer this year, according to the American Cancer Society.

While some early bone metastases do not exhibit symptoms, most bone metastases are linked to bone pain and the risk of broken bones because the bone tissue is compromised as a result of the growing tumors. Patients may also have spinal cord compression if the metastases are growing within the spine. This type of compression can lead to weakness, numbness, and paralysis as a result of nerve damage.

Typically, drugs that treat the prostate cancer can treat the tumors in the bone, as well as those in soft tissue, and can also help to prevent new metastatic tumors. These therapies include secondary hormone therapies recently approved-abiraterone acetate (Zytiga) and enzalutamide (Xtandi).

A new type of agent, radium-223 dichloride (Xofigo), a radiopharmaceutical, was approved by the US Food and Drug Administration (FDA) in May, for those prostate cancer patients who have castration-resistant, advanced disease with symptomatic bone metastases but no metastases to soft tissue. Because this alpha particle-emitting radioisotope is a calcium mimic, it hones to sites of bone turnover, including sites of metastasis, and has DNA-damaging properties.

The ALSYMPCA phase III clinical trial, recently published in the New England Journal of Medicine, demonstrated that the treatment was well-tolerated and resulted in an improvement in overall survival by 3.6 months compared with placebo (P < .001). Radium-223 also significantly prolonged the time to a first symptomatic skeletal event compared with placebo by a median of 5.8 months (P < .001). The study also showed that the therapy improved quality of life for patients.

Radium has a different mechanism of action compared with the currently approved prostate cancer therapies, according to Mary-Ellen Taplin, MD, a medical oncologist at the Dana-Farber Cancer Institute in Boston, who specializes in prostate cancer. Radium-223 does not necessarily make any objective prostate cancer measurements better, such as prostate-specific antigen (PSA) levels or measurable disease on imaging scans, but treats bone pain and does make patients live longer, said Taplin.

In general, any therapy that targets the prostate cancer and is efficacious will work to alleviate pain from bone metastases. “So patients who are responding well to abiraterone or enzalutamide, for example, probably don’t need so much denosumab or zoledronic acid to treat pain,” said Taplin. The tumors are likely relatively under control, and these patients are not at high-risk for developing skeletal-related events.

Denosumab (Xgeva) and zoledronic acid (Zometa) are a different class of agents that do not treat the prostate cancer but are approved by the FDA for patients with bone metastases to prevent or delay bone fractures, as well as spinal cord compression that results due to bone damage from the cancer. These agents have been developed as supportive care to alter the bone microenvironment and reduce skeletal-related events, said Matthew R. Smith, MD, of the Dana-Farber Cancer Institute, who also specializes in prostate cancer.

Developing agents that can prevent bone metastases in patients who have castration-resistant prostate cancer but do not yet have metastatic cancer is difficult, said Taplin. This is a difficult area of drug development because the FDA requires agents to show an overall survival advantage.

While denosumab and zoledronic acid have been studied in preventing bone metastases in prostate cancer patients, the data are so far inconclusive about the benefit in preventing bone metastasis.

Related Videos
Artificial intelligence models may be “seamlessly incorporated” into clinical workflow in the management of prostate cancer, says Eric Li, MD.
Robust genetic testing guidelines in the prostate cancer space must be supported by strong clinical research before they can be properly implemented, says William J. Catalona, MD.
Financial constraints and a lack of education among some patients and providers must be addressed to improve the real-world use of certain prostate cancer therapies, says Neeraj Agarwal, MD.
Novel anti-PSMA monoclonal antibody rosopatamab is capable of carrying a bigger payload of radiation particles, which may potentially reduce doses for patients with prostate cancer, says Neeraj Agarwal, MD.
Findings from recent studies support the use of artificial intelligence-based tools in the context of radiation therapy for patients with localized prostate cancer, according to Neeraj Agarwal, MD.
Germline testing may elucidate important mutations in patients with metastatic prostate cancer who may be eligible to receive treatment with PARP inhibitors, according to Neeraj Agarwal, MD.
In this September edition of Snap Recap, we share our highlights from Prostate Cancer Awareness Month, news in the breast cancer space, and the latest FDA updates.
Artificial intelligence programs may help introduce new care strategies that minimize the risk of adverse effects in patients with prostate cancer, according to Wayne G. Brisbane, MD.
An artificial intelligence algorithm appears to create accurate focal treatment margins in patients with prostate cancer, according to Wayne G. Brisbane, MD.
Artificial intelligence may be useful in screening for prostate cancer in patients with elevated prostate specific antigen levels who have undergone MRI, according to Wayne G. Brisbane, MD.
Related Content