In this series, we speak with cancer care practitioners about how pathways are being used in their practices, how they are being applied in a particular disease state, and what challenges remain for treatment decision-making.
For this installment, Journal of Clinical Pathways (JCP) spoke with Neal D Shore, MD, a practicing uro-oncologist and the medical director at the Carolina Urologic Research Center and Atlantic Urology Clinics, LLC (Myrtle Beach, SC). Dr Shore has conducted more than 350 clinical trials, focusing mainly on genitourinary (GU) oncology. Dr Shore discussed standard of care for prostate cancer patients specifically related to bone health and bone metastases. Topics covered include current and new therapeutic options, management of skeletal-related events or bone complications, and the importance of clinical pathways.
Please tell us about Carolina Urologic Research Center’s clinical pathways for prostate cancer patients.
We have a pathway for following patients to ensure that bone health is front and center of their GU oncologic treatment, particularly relevant for our prostate cancer patients who have a very high predisposition to develop bone metastases, and also very important for our patients undergoing androgen deprivation therapy.
Additionally, for our nonprostate GU oncology patients, we very carefully follow various guidelines, both nationally and internationally, inclusive of guidelines by the National Comprehensive Cancer Network, American Society of Clinical Oncology, American Urological Association, European Association of Urology, and European Society for Medical Oncology.
At our center, we are working toward formalizing our pathways for our GU oncology cancer patients, focusing on greater efforts toward sub-specialization. Having said that, we are always working to stay abreast of the most cutting edge data and, therefore, incorporating it into our diagnostic evaluation and management strategies.
Could you please detail your standard treatment for bone breakdown due to prostate cancer therapy?
We may initiate androgen deprivation therapy (ADT) for prostate cancer patients who have de novo metastatic disease, and sometimes for those who have a rising prostate-specific antigen (PSA) following an interventional therapy (for example, surgery and/or radiation), and therefore, these patients PSA or biochemical relapse.
We follow National Osteoporosis Foundation recommendations of evaluation, which includes a thorough family and social/lifestyle history, as well as performing a FRAX score. Also, we try, whenever allowed by third-party payers, to get a baseline bone density test (a DEXA scan) to evaluate concerns for patients who might be predisposed to osteoporosis.
Once we assess bone densitometry (a DEXA scan and a FRAX score), we also check vitamin D and calcium levels. We will regularly review with the patient the importance of supplemental vitamin D and calcium as well as the absolute supplemental importance of avoiding a sedentary lifestyle. We encourage an achievable exercise regimen and a nutritional guidance, usually consistent with a heart healthy diet.
Additionally, some other recommendations include well fitting shoes and lifestyle strategies to reduce the risk for falls, such as home safeguarding by promoting enhanced lighting and eliminating low profile stools, loose carpets, any kind of slippery materials, especially in the bathroom and in the garage area.
We do stratify these patients based upon their FRAX score, which largely is gender, country, and family history based regarding their prior histories of their own personal risk of fracture or experience of fracture, family history as well as their bone densitometry testing, and clearly starting on ADT, which has significant risk because of the declines in both testosterone and estradiol.
What are the benefits of a few of the current therapy options in this setting?
As I mentioned, we are very strong proponents of exercise regimens, proper diet, vitamin D and calcium supplementation, avoidance of excess of alcohol, and trying to incorporate smoking cessation. We are also strong proponents of the bone health agents or bone targeted therapies, and we have had long-standing utilization of both bisphosphonates and denosumab.
Generally, I tend to prefer utilizing denosumab. I find it easier to administer, and I believe the data which suggest it has a more robust bone health impact in terms of bone fragility issues as well as in bone metastatic disease. Very rarely, access may be impeded due to cost concerns.
How do you ensure the latest approaches to therapy for patients are rapidly incorporated into practice?
I carefully review the use of concomitant bone targeted therapies with the newly approved castration-resistant prostate cancer (CRPC) agents, primarily the novel hormonal agents (NHAs) consisting of abiraterone, enzalutamide, and, most recently, apalutamide.
Soon, we will most likely see the approval of darolutamide, and then we will have 4 NHAs. It is important to review concomitant bone targeted therapy with radium 223 as well as with combinations of radium 223 with the NHAs. Similarly, we review the use of bone targeted therapies with taxane-based therapy inclusive of docetaxel and cabazitaxel.
Overall, with the caveat that it does require some additional clinic visits to receive their bisphosphonate and/or denosumab as well as with the caveat that (at least in the bisphosphonates), it is an intravenous preparation as opposed to denosumab, which is administered subcutaneously. Creatinine monitoring with bisphosphonates is required as opposed to denosumab. Both bisphosphonates have concerns regarding the small but real risk of developing osteonecrosis of the jaw (ONJ).
I place all of these issues into consideration for proper monitoring as well as oral health inspection, and consider the overall risk benefit analysis of both of the bone targeted therapies as it relates to bone fragility avoidance and skeletal-related events complications.
Since we have had a rather rapid approval over the last 8 to 9 years of many new advanced prostate cancer therapies, we have had studies looking back retrospectively upon the patients in both the treatment arms and the control arms who did or did not receive bone targeted therapy.
It seems that the evidence prompts us to strongly encourage patients to be on some form of bone targeted therapy certainly in the nonmetastatic CRPC disease as well as in all aspects of metastatic disease confirmed by radiographic imaging CRPC and certainly within those who present with de novo metastatic disease with bone involvement.
How do you balance the need for standard treatment consensus with the need to optimize care?
It is always a very important question as it relates to sequencing and combining therapies. I do think that the bone targeted therapies are ideally suited for concomitant therapy with all of the metastatic CRPC treatments, inclusive of sipuleucel T, abiraterone, enzalutamide, apalutamide, as well as radium 223, docetaxel, and cabazitaxel, certainly as long as patients have bone metastases.
These patients need to be monitored, as I said earlier, for concerns regarding ONJ. As it relates to denosumab, usually for metastatic CRPC patients, I will provide therapy monthly for a 2-year period. After 2 years, I will elongate the dosing schedule with denosumab to every 2 to 3 months and similarly with bisphosphonates.
What are some challenges to optimizing therapeutic decision-making that you continue to see in your practice? How do you anticipate these challenges might be overcome?
New data regarding prostate treatment has been coming out at a rather breakneck speed since 2010. Certainly, in the last 6 to 7 years, kidney cancer therapies have burgeoned as well. In the last 3 years, bladder cancer has been equally logorithmic in terms of new data and new studies, which are enrolling for various fascinating combinations of therapy. Data is emerging very quickly. We have more trials, oftentimes, than we have patients available to fill all the trial accrual goals.
As we continue to learn more in terms of genomic sequencing and various other biomolecular markers, we will become more precise in certain types of therapeutic recommendations. This is an exciting area, so it is not going to always be a one size fits all approach. With molecular markers, which will allow us to select a more optimal treatment for a more durable response, we will have more individualized approaches to patient cancer care, whether it is an androgen receptor signaling inhibitor, a taxane-based therapy, or radiopharmaceutical. In the future, we will have some antibody drug conjugates, additional immunotherapies, and other therapeutics with unique targeted pathways such as the poly (ADP-ribose) polymerase inhibitors.
The challenge will be for busy clinicians to make sure that they are staying abreast of all the new developments and aware of all the different possibilities for optimizing patient care. What I try to do, and as we all do globally, is to stay on top of the literature, whether it is through publications written for web-based meeting attendance, presentations, advisory boards, etc. Pathways are very important and helpful to ensure that there is not significant outlier management of patients and, at the very least, that there is a full understanding of the level one evidence that has been established for advanced cancer patients.
There is an enormous amount of work that goes into creating a well-researched clinical pathway or algorithm. I am actually involved in developing 2 pathways right now through the Large Urology Group Practice Association. We are doing a pathway on the use of ADT in prostate cancer as well as a pathway for CRPC management in advanced prostate cancer clinics. Both of these projects will hopefully assist community medical oncologists, urologists, and radiation oncologists in their goal to optimize patient care.
