Carrie Tompkins Stricker, PhD, RN, ANP-BC:
Welcome everyone to this virtual roundtable about bone health and oncology for advanced practitioners. This is a case-based approach, and I'm Carrie Tompkins Stricker. I am an associate professor of nursing at the Thomas Jefferson University in Philadelphia, Pennsylvania, and an oncology nurse practitioner with over 25 years of experience caring for individuals with cancer. Joining me today are three of my colleagues. We have a very representative group: a physician and two other advanced practitioners in addition to myself. I'd like to begin with allowing Dr. Paul Sieber to introduce himself.
Paul Sieber, MD:
Morning. Paul Sieber. I'm a urologist in Lancaster, Pennsylvania, and I function in my group as the advanced prostate cancer chairman.
Carrie Tompkins Stricker, PhD, RN, ANP-BC:
Thanks Paul. And next I'd like to have Christine introduce herself.
Christine Cambareri, PharmD, BCPS, BCOP, CSP:
Hi everyone. My name's Christine Cambareri. I am an outpatient oncology pharmacy specialist practicing at the University of Pennsylvania, focusing on solid tumors.
Carrie Tompkins Stricker, PhD, RN, ANP-BC:
And last but not least, we have Saneese. Saneese, go ahead.
Saneese Stephen, MPAS, PA-C
Hello everyone. Thanks for inviting me. My name is Saneese Stephen. I've been a physician assistant at MD Anderson for the past 10 years, working in GU medical oncology.
Carrie Tompkins Stricker, PhD, RN, ANP-BC:
So just some background, which is probably familiar to many of you on this lecture and recording. We all treat cancer, right? Well, its treatment and the cancer itself can contribute to compromised bone health, leading to painful fractures and loss of mobility that ultimately impairs quality of life. Certain types of cancer have a very predictable pattern of spread to bone. Some of these are those you've heard mentioned already by our speakers. Prostate cancer, breast cancer, and multiple myeloma are among the top. So skeletal-related events, or SREs as we'll refer to them…what are they? Bone metastases most frequently affect the axial skeleton and often cause skeletal complications that are known as these SREs or skeletal-related events.
What are they? Well, they're the fractures, as we've already mentioned. Radiotherapy to the bone is actually also considered an SRE. So is surgery. So is spinal cord compression, and so as hypercalcemia. These events are associated with significant loss of mobility, loss of function, reduced quality of life, increased healthcare expenditures and worse survival. All outcomes we as care providers of individuals with cancer wish to avoid on behalf of our patients.
In prostate and breast cancers in particular, we have to consider the hormonal context and why these individuals are already at great risk of bone loss and bone events themselves even prior to metastatic disease. So why is that? I'll talk a little bit about breast cancer, and then I'm going to hand it off for Saneese to talk a little bit about prostate.
In breast cancer, estrogens play a crucial role. Well, where else do estrogens play a crucial role? In bone growth maturation and maintenance of skeletal integrity. The net action of estrogens on bone is to decrease bone resorption, to drop bone resorption. There are estrogen receptors in the bones expressed on osteoblasts that builds bone, and osteoclasts, which break down bone. And when we interfere with estrogen receptors and we interfere with the effects of estrogen by treating breast cancer, we also put the bone at risk.
I'm going to pass it off to Saneese now. He'll tell you a little bit about prostate cancer and bone loss.
Saneese Stephen, MPAS, PA-C:
Thanks, Carrie. Very similarly to breast cancer, estrogen is also important in men. Many people realize that testosterone is our primary hormone, but testosterone is converted to estradiol via aromatase activity in peripheral tissues. And estradiol becomes a primary estrogen in men and it's involved in bone resorption […], like Carrie mentioned.
So when we're decreasing testosterone, it's multiple ways affecting bone density and bone strength in men. That's why you see testosterone-depleting therapy cause four times as much loss in bone integrity and bone health in people who are taking androgen deprivation therapy. So it's very complicated dynamics between bone health and prevention of bone deteriorating medications. So I think it's important to talk more about it, as we will later on. It's important to note that AR and ER, androgen receptors and estrogen receptors interact with osteoblastic precursors, as Carrie mentioned, and we have significant deleterious effect from androgen receptor drugs, such as Xtandi (enzalutamide), which you'll hear later in one of our cases. But I'll talk more about this as we discuss the cases upcoming.
Carrie Tompkins Stricker, PhD, RN, ANP-BC:
Thank you, Saneese. One thing that's important to note in considering differential diagnosis is that metastatic involvement of the skeleton, both axial and appendicular, typically affects sites across both axial and appendicular and causes pain and bony tenderness, whether subjectively experienced tenderness and/or upon palpation in really acute bone disease or fracture.
There are a variety of clinical practice guidelines addressing diagnosis and treatment of bone mets and prevention of SREs. These include ESMO and ASCO. ESMO is the European Society of Medical Oncology. ASCO is the American Society of Clinical Oncology, and the latter, ASCO, particularly has guidelines in breast cancer, whereas ESMO'S clinical practice guidelines cover all cancers with bone metastases or bony involvement like multiple myeloma.
So what do these address? ESMO talks about imaging and biopsy recommendations that vary by disease. CT and MRI are recommended typically in myeloma. In solid tumors, bone scans are traditionally used for bone mets evaluation in solid tumors, but there has been a huge increase in the use, appropriately, of PET scan. PSMA scans sometimes also have a role in staging for specific situations in solid tumors and FDG PET CT imaging is particularly valuable in addressing early evaluation of response.
You will see on your slide a comparison of the ASCO guidelines that I mentioned for the role of BMAs or bone-modifying agents in metastatic breast cancer compared to bone health ESMO, the European guidelines. And what they currently state in terms of initiation of therapy once bone mets are diagnosed, is that all metastatic breast cancer with evidence of bone mets should be treated with BMAs. However, there's no evidence to initiate these BMAs or bone-targeted agents in patients who don't have evidence of bone destruction. They don't take a stand on preference of one bone modifying agent or the other. The same is true with ESMO, who states that BMAs should be initiated at diagnosis of bone mets and considered throughout the course of disease.
