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Charles Nguyen, MD, on Bone-Modifying Agents in Metastatic Prostate Cancer

– Guideline adherence is suboptimal, highlighting the 'unique challenge' of caring for such patients


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Patients with metastatic prostate cancer who were older, Black, or had more comorbidities were less likely to receive bone-modifying agents (BMAs) to prevent skeletal-related events (SREs), researchers reported in .

Charles Nguyen, MD, of the University of Michigan in Ann Arbor, and colleagues analyzed data on 3,980 men with metastatic castration-resistant prostate cancer (mCRPC) in the Veterans Affairs system from 2010 to 2017. A total of 48% of these patients had a diagnosis of bone metastases, and 47% received a BMA.

Clinical guidelines recommend BMAs in patients with mCRPC and bone metastasis to prevent SREs. Decreased BMA use was associated with advancing age (OR 0.85 per 10 years, 95% CI 0.78-0.92), a Charlson comorbidity index of 2 or higher (OR 0.76, 95% CI 0.63-0.93), and Black race (OR 0.83, 95% CI 0.70-0.98).

"These observations highlight the unique challenges of caring for patients with mCRPC and the need for future studies to increase BMA use in these populations," the investigators concluded.

Nguyen speculated on possible explanations for the findings and discussed future research in the following interview.

In your study, 48% of patients had a diagnosis of bone metastases and 47% received a bone-modifying agent. Does this suggest good compliance with treatment guidelines in the patients you studied?

Nguyen: It is known that diagnosis codes for bone metastases are limited by the low sensitivity, which results in under-reporting of bone metastases in mCRPC, since it is well known that most patients with mCRPC (approximately 90%) have bone involvement. Given that all patients with mCRPC and bone metastases are not fully identified in our cohort, the BMA adherence rate in our study is suboptimal, which is consistent with other studies that evaluated BMA prescribing in mCRPC.

Why are BMAs critical supportive therapy in older patients with mCRPC?

Nguyen: There is overwhelming and clear data from randomized, phase III trials that show that these agents delay and lower the risk of SREs in patients with mCRPC. SREs can be associated with pain and complications -- e.g., bone fracture and cord compression -- that may require surgical intervention and radiation therapy.

These events can have a negative impact on patient mortality and quality of life, which are particularly important in older patients with mCRPC. Thus, BMAs are valuable supportive agents in this patient population.

Why do you think the older patients in your study were less likely to receive BMAs?

Nguyen: There are unique factors that are often taken into account when caring for older patients with mCRPC, including underlying comorbidities, life expectancy, and the patient's preferences on treatment. These factors, in addition to clinician's views on treating patients with advanced age, may influence treatment decisions, including BMA use, in older patients as oncologists may want to minimize therapy toxicities. However, BMAs generally have a lower toxicity profile compared with cancer-directed therapies and should still be offered to older patients given the strong benefits of BMA therapy.

Why is BMA therapy important for mCRPC patients with multiple comorbidities?

Nguyen: In patients with localized prostate cancer, higher Charlson comorbidity index scores were associated with time to first osteoporotic fracture. Patients with mCRPC who have comorbidities are therefore at potential risk of SREs which have negative implications on quality of life and mortality. Thus, BMAs are also critical in patients with mCRPC and underlying comorbidities.

Why do you think patients with more comorbidities in your study were less likely to receive BMAs?

Nguyen: Similar to the situation with older patients with mCRPC, treatment decisions may be complex in patients with mCRPC with more comorbidities. Factors such as the patient's life expectancy and goals on therapy may impact these decisions, including the decision to prescribe a BMA. Given the risk-benefit profile of these agents, BMAs should still be offered to patients with mCRPC with underlying comorbidities.

Why do you think the Black patients in your study were less likely to receive BMAs?

Nguyen: Our findings are similar to prior reports of the disparities in bone-modifying agent prescribing in other cancers such as multiple myeloma. While racial disparities in cancer care have been partly attributed to inequities in healthcare access and discrimination within the medical system, our observation was particularly surprising given that our cohort received care in a national healthcare model. The exact reasons remain unknown, but future studies should evaluate the reasons for inequitable care.

Read the study here.

The study was supported by the Prostate Cancer Foundation, the National Cancer Institute, and the Rahr Foundation.

Nguyen reported no conflicts of interest.

Primary Source

JCO Oncology Practice

Source Reference:

ASCO Publications Corner

ASCO Publications Corner