Bone-Modifying Agents in Metastatic Prostate Cancer – Guideline adherence is suboptimal . . . Dr. Nguyen MedPage interview by Jeff Minerd

[cujoe]

This MedPage article was the "Featured Study" on this recent ASCO Reading Room Article Series. The interview of first author Dr. Charles Nguyen spotlights the underutilization of bone modifying agents (BMAs) in mCRPCa patients found in their study. (Linked below.) It is probably safe to assume that his comments also apply to all stages of PCa patients in treatment, and especially to those on any form of SOC ADT.

Unfortunately the article, abstract, nor the linked paper (PDF) report the use of any dietary profiles or supplementations that are known to support bone health whether on treatment or not. As we all get older many gradual changes affect our bone health. One is the decline in testosterone prior to and after starting ADT - as estrogen is essential for bone health and men derive their estrogen from testosterone: i.e., no T = no E2 ~ no support for bone health. The other is that the calcium + Vit D that is often prescribed for men (and women) when their bone health is challenged by age and/or treatment has been repeatedly show to have little to no positive effect on bone health aka "density" - without the concurrent supplementation with other vitamins and minerals that direct Ca to bones and not elsewhere; i.e., kidneys, arteries, and joints. (And, BTW, how many of you patients had a Dexa-scan when you were first diagnosed with PCa or started treatment?)

Nowhere in the study was there any mention of the dietary and lifestyle components so important to bone health in aging men. Doctors are woefully unknowledgeable about diet and lifestyle, in general, and seem more than willing to prescribe expensive meds rather than to educate and assist the patient effect meaningful modifications to diet and lifestyle. When habitual, such changes can provide lasting results without the need for the perpetual use of costly meds with their potential known/unknown SEs.

Peter Attia says what we need is "Healthcare 3.0" that is focused on prevention rather than treatment. The cost benefit of such a system of preventative care would save billions of dollars that we now spend annually on chronic diseases that are almost totally related to diet and lifestyle. While we wait, we get studies like this, that prove how ineffective the current healthcare system is in even identifying the true cause(s) of a disease state related to aging - plus treatment. Coupled with a near-complete lack of prevention, the solution prescribed for the patient is one that comes completely from big pharma - with both the monetary cost and SEs of the scripted meds for them to bear.

* * *

Charles Nguyen, MD, on Bone-Modifying Agents in Metastatic Prostate Cancer – Guideline adherence is suboptimal, highlighting the 'unique challenge' of caring for such patients, by Jeff Minerd , Contributing Writer, MedPage Today October 18, 2024:

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 JCO Oncology Practice.

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 (see link below):

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

Nguyen reported no conflicts of interest.

Source Reference: Nguyen CB, et al "Determinants of bone-modifying agent prescribing for metastatic castration-resistant prostate cancer in a national health care delivery system" JCO Oncol Pract 2024; 20: 59-68

* * *

The MedPage Today article is here:

Charles Nguyen, MD, on Bone-Modifying Agents in Metastatic Prostate Cancer – Guideline adherence is suboptimal, highlighting the 'unique challenge' of caring for such patients, by Jeff Minerd , Contributing Writer, MedPage Today October 18, 2024:

medpagetoday.com/reading-ro...

And the source paper (abstract only and link to full report PDF download - @ bottom of abstract page) is here:

Determinants of Bone-Modifying Agent Prescribing for Metastatic Castration-Resistant Prostate Cancer in a National Health Care Delivery System, JCO Oncology Practice, ORIGINAL REPORTS, Volume 20, Number 1, November 02, 2023:

medpagetoday.com/reading-ro...

* * *

Stay S&W, Ciao - cujoe

PS for those interested, here is a brief description of Attia's HC3.0:

awiboca.com/blog/outlive

[MateoBeach]

in the spirit of Healthcare 3.0, prevention requires looking ahead and identifying important risks and then mitigating them. With PCa that is not cured with initial therapy (surgery or radiation) this is identified at BCR. It is not curable for most. It will lead to the development of castrate resistance when ADT is instituted and continued. This will lead to bone mineral depletion and high risk for SREs. End stage mCRPC has very high probability of bone mets.

Therefore I believe bone protective regimen should be started at BCR, and not wait for osteoporosis, nor castrate resistance nor bone metastasis to be identified. It is coming if we don’t act.

I started bone protection at BCR two years after my RP surgery. A weekly dose of generic alendronate and adequate Calcium and vitamin D. That was in 2009. Later I switched to denosumab which I continue. I remain mHSPC with no bone mets on any scan. Just my opinion. MB

[Lizzo30 in reply to MateoBeach]

It says in your profile you had estrodial patches - surely the patches are the reasons your bone health is good ?

[MateoBeach in reply to Lizzo30]

It certainly helps. But I was only on the patches for 8 months when on ADT after SBRT and pelvic RT. My high T my BAT maintains my E2 levels now. Still also using Xgeva just every 6 months to help prevent bone metastasis.

[cujoe in reply to MateoBeach]

MB - Trust you are safely back in your winter season residence and already enjoying warmer weather. Weather here in my neighborhood has been exceptional for the last month or so, and now that peak hurricane season has passed, it seems the weather spirits have spared us the pain being experienced elsewhere in the SE. I expect your rehab will also be favored by the warmer weather over the winter to come.

As for my commentary on the post, I would never dispute the need for pharma intervention for bone health for those patients on ADT or other treatments that degrade density and increase fracture risk. (And for post-menopausal women whose bone loss goes downhill radically after ~ age 50.) My contention is that most people over 65 (male and female, but esp. women post-menopause), regardless of having cancer or not, should have a baseline Dexa Scan as a routine part of their healthcare. (Who would prescribe that and how it is paid for is really a secondary issue, as I decided long ago to willingly pay out-of-pocket for labs that my docs will not order.) Dexa results that indicate a risk for bone fracture should be first put on a diet/lifestyle and supplement regime (as needed) to support/improve bone density. If bone-density declines further, pharma agents would then be considered - and the diet/lifestyle/supplements continued.

As for PCa patients, it seems all patients who are not already being monitored for bone health on a regular basis, should have a Dexa evaluation at the time of their diagnosis. That way they could take proactive steps (incl. diet, lifestyle, supplements, and pharma - as required) to maintain/improve bone health and curb any risk of decline before needing treatment for PCa. And ALL patients on treatment, esp. ADT, should be monitored via Dexa scans at a regular interval, say, at least once-a-year.

The "more complete" vitamin and mineral supports for bone health for some reason seem to be unknown to most of the healthcare industry, including PCa & BCa oncologists. The single most-effective intervention that contributes to bone-density, assuming adequate nutritional support, is simply the lifting of heavy weights aka "weight-bearing exercise". Treadmills, ellipticals, swimming, walking do not provide the sort on impact to bones that will engage the metabolic functions to remodel and strengthen them. However, for physical activity to improve bone density, the "more complete" nutritional components are essential.

I first learned what vit/min beyond Vit. D and Ca were essential to support bone health from Nal and Patrick. Here is a link to a reply about kidney stones that lists the main ones with links to research supporting their roles in bone health.

healthunlocked.com/fight-pr...

Y'all stay S&W - and go lift some heavy stuff today. Your bones will thank you for it.

Ciao - cujoe

BTW, this reply is directed to our general audience and not you, MB 🌴, specifically. I'm pretty sure you are more than aware of the full dietary components and active lifestyle needed to build and maintain strong bones.☮