I hope that many of you took notice of the recent estimates for 2018 by the American Cancer Society in the latest 

 At first glance, the trends really have not changed: Prostate cancer continues to be the most common newly diagnosed solid tumor in men over 50 years and the second leading cause of cancerspecific mortality.

The good news is that the number of new cases is relatively stable, with just over 160,000 estimated for this year. The sobering statistic, however, is that the number of deaths projected for patients with prostate cancer for the year has risen (164,690 for 2018 vs 161,360 in 2017). The decrease in the number of new cases over the past 5 years, and this 2% rise in prostate cancer mortality, is no doubt directly related to the ill-fated “D” recommendation attributed to prostate-specific antigen (PSA)—based screening. This decision was handed down by the United States Preventive Services Task Force (USPSTF) in 2012 despite unified protests from our major organizations, including the American Urological Association, the Large Urology Group Practice Association, the American Association of Clinical Urologists, and the Society of Urologic Oncology. Combined with the rising incidence of metastatic disease in men between ages 55 and 69, the urology world needs to stand up and take notice.

Many years ago, a colleague and I debated about the role we, as urologists, play when a patient is referred to us from a primary care physician with a singular elevation of their PSA value. His practice and logic was to biopsy all these patients because if he did not, the patient would just go someplace else to get the biopsy performed. This was probably a not-too-uncommon practice of many urologists in the community dating 10 to 20 years. However, our understanding of the limitations of PSA, prostate cancer heterogeneity, and the availability of adjunctive testing— both genetic assays and imaging based&mdash;truly puts us in the best position to manage these patients who have been referred for our expertise and knowledge base, not just our technical skills.

As we have articulated many times in this publication, it is incumbent on us as specialists to be the recognized leaders and experts in the diagnosis and management of prostate cancer and not cede that mantle to any of our colleagues. So, what are the areas that require our complete and thorough understanding so that we can better serve our patients, especially in this world of value-based medicine:

Which patients need an initial biopsy to diagnose significant prostate cancer, and what tests are available to aid in that decision?

Which patients with an initial negative biopsy require a repeat biopsy?

When is active treatment/intervention needed versus active surveillance for localized prostate cancer?

In the setting of a patient definitively treated but who has a biochemical recurrence, when is it appropriate to start androgen deprivation therapy (ADT)?

Early identification of metastatic disease in the patient with castration-resistant prostate cancer (CRPC).

Understanding of the various therapeutic options for patients with hormone-naïve and metastatic CRPC, as well as the adverse effect profiles of these agents, including ADT.

Understanding the role of molecular and hereditary testing for patient management and family counseling.

Understanding the utilization of new imaging technology.

As we are well aware, the rapid proliferation of new data in all of these areas can be quite daunting and can make it difficult to stay current, especially for individual practitioners or even those with well-established large group practices where there is an element of sub-specialization to some degree. That is no excuse for us to not take the opportunity to go out and educate our referring doctors and the public on how the urology community manages these complex issues. If we fail in these endeavors, we will become nothing more than dancing monkeys, relegated to perform when instructed to do so by our referring physicians who will view us as nothing more than noncognitive proceduralists. We cannot allow that to happen, given our responsibilities to our patients and the training of our future urologists.

American Cancer Society. Cancer facts and figures 2018. ACS website. cancer.org/ research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2018.html. Published 2018. Accessed January 12, 2018.

Articles

Prostate cancer continues to be the most common newly diagnosed solid tumor in men over 50 years and the second leading cause of cancerspecific mortality.

A Call to Arms in Urology

It may be true that most people do not enjoy staff meetings, but the partners at Wichita Urology, the largest independent urology practice in Wichita, Kansas, have built their success over 60 years partly by holding frequent meetings, which they say build camaraderie and make it possible to address needs quickly.

Meetings, they say, create a transparency that prevents employees from being broadsided by any changes. “All the physicians come together at the board meetings. Even if you’re not yet a partner you still attend, and we hold board meetings 3 times a month,” said Twila Puritty, CEO of Wichita Urology. This makes the practice nimbler and, as a result, things that need doing don’t languish on the back burner. “We are able to accomplish a lot of things in a short period of time compared with other groups who don’t meet as frequently,” she said. This collaborative style also allows for everyone’s voice to be heard when practice-changing decisions are made.

Another pillar of the administrative structure at Wichita Urology is a collection model that ensures the physicians are fairly and efficiently paid for their hard work, Puritty explained. The practice requires payment upfront for elective surgeries—before the procedures take place. “We used to write off thousands of dollars for elective surgeries that patients didn’t pay for after receiving surgery. So, we adopted a policy that surgeries would be classified as either urgent or elective, and if they’re elective the surgery isn’t scheduled until the patient pays the out-of-pocket amount,” Puritty said. It was felt that these nonessential unpaid surgeries were not only an inefficient practice but also cost physicians time that they could have spent at home with their families.

Under the revised policy, the cost of the elective surgery is explained to patients, and numerous attempts are made to ensure payment is received upfront. The surgery will usually be rescheduled until that requirement is met. However, it sometimes happens that the practice will do an elective procedure without payment and accept the unpaid bill as a cost of doing business.

Wichita Urology has grown organically, without merging with any other urology groups. It was founded by 3 urologists in 1955 and now has 9 physician partners. The support staff numbers 92 employees, including 84 who are full time and 8 who are part time. Although the practice has many employees, its efficiency is high, and this enables clinicians there to see a high volume of patients, Puritty said. From 2016 to 2017 the group saw 19,427 patients.

Wichita Urology is spread out over 3 offices in the south-central Kansas metropolis. The main office on the east side of town is large enough to have 3 clinics operating at once. By contrast, their west-side office offers just 1.

Physicians at the practice see adult and pediatric patients with all stages of prostate, bladder, and kidney cancer. “We have individuals from first diagnosis to those who walk in with metastatic disease. We not only get referrals for end-stage disease, we see every type,” said Timothy A. Richardson, MD, a physician partner.

The urology group participates in many clinical trials for prostate cancer and a smaller number for patients with renal or bladder cancer. Wichita Urology also enrolls patients in trials for general urologic disorders, such as overactive bladder and benign prostatic hyperplasia. There are no medical oncologists on staff, but the practice works closely with a local medical oncology group to address patients’ needs for chemotherapy or other specialized cancer treatments. Following outside care, patients usually return to Wichita Urology to resume treatment.

The practice often can provide in-house treatment for a wide spectrum of a patient’s needs. For example, the practice can provide surgical interventions for patients with resectable cancers. “For prostate cancer, we take care of those patients from diagnosis. If they need chemotherapy, we send those on, but we still try to manage everything else,” Richardson explained.

In 2014, Wichita Urology opened an office that is dedicated to radiation therapy. The availability of radiation oncologists enhances the practice’s ability to treat patients in-house. The practice also has an outreach program for about 15 communities. Wichita Urology physicians travel to those offices regularly for clinics that may be held multiple times per week.

Wichita Urology’s commitment to these outreach clinics often stems from hospital requests for urology coverage, according to Puritty. It is not always possible to provide support for these outside clinics, either because of a lack of staff or because a location is too far from Wichita Urology’s offices. “We can’t always say yes,” she said.

One of the most important additions to Wichita Urology is their advanced prostate cancer clinic, which they opened in 2017 to address the increasing complexity of advanced prostate cancer care. Richardson serves as the lead physician and “champion” of that clinic. “Advanced prostate cancer has become so convoluted and confusing. There are more therapies being approved every day.” To address patients’ need for access to quality care and Wichita Urology’s need for efficiency of operations, an advanced prostate cancer clinic was developed that could work with just 1 or 2 doctors, Richardson said.

Wichita Urology strives to offer patients cutting-edge technologies and treatments, but its doctors also want to ensure that patients get the most appropriate care. Puritty said an example of this is a current initiative to start dispensing catheters directly to patients. She said group discovered that a vendor they worked with previously was dispensing catheters based on what made good financial sense to the vendor rather than what was most appropriate for patients’ needs.

The physicians pay close attention to the many drugs in development and look forward to being able to give their patients therapies that offer better outcomes. “There are about 300 drugs in development now, and there are a lot of drugs on the horizon that are going to be approved for us to use earlier and in different situations,” Richardson said. He anticipates that some of those drugs will become available as soon as the first or second quarter of this year.

Richardson and his colleagues also recognize the value that genetic counseling can bring to cancer treatment. They currently offer several genetic tests to patients with prostate cancer. The practice works with several genetic counselors, including one who is associated with a hospital in Wichita and another with whom patients can speak by phone.

The practice is also investigating telemedicine and how it can reduce the distances their physicians have to travel. Because they serve so many clinics across Kansas, including some that are hours away from Wichita, telemedicine would allow physicians to treat patients remotely who may not have been reachable before. “The travel burden on a busy urologist can be a killer on their productivity,” Puritty said.

Wichita Urology is vigilant about monitoring changes in payers’ payment policies, and practice members are confident that their in-house efficiencies will protect them from the potential revenue losses that can result from payment policy changes. “There are all these conversations about reimbursement, such as the Medicare Access and CHIP Reauthorization Act and the Meritbased Incentive Payment System, and how are we going to be impacted—negatively or positively.” Purrity said that internal policy changes can help to offset external pressures. The practice’s decision to aggressively pursue payment upfront for elective surgeries is one such example, she said.

Wichita Urology, the largest independent urology practice in Wichita, Kansas, have built their success over 60 years partly by holding frequent meetings, which they say build camaraderie and make it possible to address needs quickly.

Urology Practice Succeeds With Transparency, Upfront Payment Model

The use of androgen deprivation therapy (ADT) in prostate cancer is now a well-established treatment regimen. Whether in the neoadjuvant setting with high-risk prostate cancer, in biochemical recurrence after definitive therapy, or in the setting of metastatic disease, its use can be described as “routine.” Unfortunately, ADT is associated with an increased risk for bone fracture.

An analysis of SEER-Medicare records of more than 50,000 men with a diagnosis of prostate cancer demonstrated a dose-dependent association between the use of gonadotropin-releasing hormone (GnRH) agonists and the risk of fracture.

 Nineteen percent of men who received ADT for 12 to 60 months experienced a fracture compared with only 12.6% without ADT who had fractures in the same time period (

 <.001). Men treated with 1 to 4 doses of GnRH had a fracture risk similar to those with no ADT, and those treated with 9 or more doses had a fracture risk similar to that of men who underwent orchiectomy, which was associated with the highest rate of fractures.

This study could not rule out pathologic fractures; however, the risk of fracture with ADT was not significantly altered when the analysis was restricted to early-stage disease. Similarly, another large database analysis of men with prostate cancer treated with or without GnRH demonstrated a significantly increased risk for fracture in those treated with GnRH; the relative risk for hip fracture with ADT was 1.76 (95% CI, 1.33-2.33).

ADT is associated with an accelerated rate of bone resorption. In general, in an older man, the normal rate of loss of bone mineral density (BMD) is approximately 0.5% to 1.0% per year. With bilateral orchiectomy, the rate of loss in BMD is estimated at approximately 8% to 10% over the first 1 to 2 years,

 whereas the subsequent rate of BMD loss with ADT is 3% to 7% per year.

It is important to understand that the rate of BMD loss is greatest when first starting ADT and decreases over time.

 This picture is not dissimilar from patients receiving glucocorticoids, a therapy clearly associated with fracture risk.

The American Urological Association (AUA) guidelines, however, offer just 2 options for the management of bone health:

Clinicians should offer preventive treatment (eg supplemental calcium, vitamin D) for fractures and skeletal related events to patients with castration-resistant prostate cancer (CRPC).

Clinicians may choose either denosumab (Prolia) or zoledronic acid when selecting a preventive treatment for skeletal related events for patients with metastatic CRPC and bony metastases.

With that background, urologists need additional information to better understand risk assessment, monitoring, and appropriate treatments for these patients.

As a clinician assesses whether a patient should initiate ADT, there are appropriate minimal steps to take to address bone health. First, obtain a bone health history, including assessing loss in height as an indicator of prior vertebral compression fractures; a personal and family history of fragility fractures, assessing calcium and vitamin D intake; smoking history; ethanol consumption; history of falls, and review of prior BMD assessments. This may not be in the usual routine of a urologist; for example, a fragility fracture is any fracture from a standing height or an asymptomatic vertebral compression fracture.

Figure 1. FRAX Fracture Risk Assessment Tool

The free online World Health Organization Fracture Risk Assessment Tool (FRAX), which can be used with or without BMD data (FIGURE 1

) is one suggestion. FRAX estimates the 10-year risk of either a major osteoporotic fracture or a hip fracture. FRAX was developed to calculate the 10-year probability of a hip fracture and the 10-year probability of a major osteoporotic fracture (defined as a clinical vertebral, hip, forearm, or proximal humerus fracture), taking into account femoral neck BMD and clinical risk factors (TABLE).

Table. Clinical Risk Factors Included in the FRAX Fracture Risk Assessment Tool6

Suggested thresholds for pharmacologic intervention include a 20% or greater risk of major osteoporotic fracture risk in 10 years or a 3% or greater risk of hip fracture in 10 years; however, treatment decisions must be made based on the individual’s situation. FRAX is not reliable once patients are receiving antiresorptive therapy.

Second, the National Osteoporosis Foundation (NOF) lists a host of laboratory studies a physician could obtain. At a minimum, the serum chemistry needs to include calcium, renal function, phosphorus, magnesium, vitamin D, and testosterone levels. The last 2 lab values, in particular, if abnormal, indicate that a patient is at risk for osteopenia and/or osteoporosis at baseline.

Third, assess the patient’s BMD. The result may provide the diagnosis of osteoporosis or osteopenia. A low BMD is associated with a high risk of fracture. If low bone mass is identified at baseline during ADT, consideration should be given to secondary causes of osteoporosis, such as primary hyperparathyroidism or vitamin D deficiency. It is estimated that for each standard deviation (SD) drop in BMD, the risk of fracture increases 1.5- to 2.5-fold, thus making the measurement of BMD for fracture risk assessment similar to that of blood pressure for stroke.

BMD is best evaluated with dual energy x-ray absorptiometry (DXA). DXA measurement of the hip and spine is used to establish or confirm a diagnosis of osteoporosis, predict future fracture risk, and monitor patients. Areal BMD is expressed in absolute terms of grams of mineral per square centimeter scanned (g/cm

) and as a relationship to 2 norms: compared with the BMD of an age-, sex-, and ethnicity-matched reference population (Z score) or compared with a young-adult reference population of the same sex (T score). The difference between the patient’s BMD and the mean BMD of the reference population, divided by the SD of the reference population, is used to calculate T scores and Z scores.

Typically, T scores are used to assess risk. However, T scores are less reliable for men with hip replacements and sclerotic changes in the spine resulting from osteoarthritis. Thus, forearm DXA may be required to obtain an accurate risk assessment. In addition, a vertebral fracture is consistent with a diagnosis of osteoporosis, even in the absence of a normal bone density diagnosis, and is an indication for pharmacologic treatment with osteoporosis medication to reduce subsequent fracture risk. Most vertebral fractures are asymptomatic when they first occur and often are undiagnosed for many years. Proactive vertebral imaging is the only way to diagnose these fractures. The finding of a previously unrecognized vertebral fracture would change the diagnostic classification and subsequently alter future fracture risk calculations.

Independent of BMD, age, and other clinical risk factors, the presence of a single vertebral fracture increases the risk of subsequent fractures 5-fold and the risk of hip and other fractures 2- to 3-fold.

 Vertebral imaging can be performed using a lateral thoracic and lumbar spine x-ray or lateral vertebral fracture assessment (VFA), available on most modern DXA machines. VFA thus can be easily performed at the time of DXA assessment. Both DXA and vertebral fracture assessment are recommended by the NOF in these high-risk patients.

Figure 2. BMD Versus Fracture Rate and Incidence

There are other ways to measure bone loss, such as heel ultrasound (QUS), quantitative computed tomography (QCT), and peripheral DXA (pDXA). However, these are not the gold standard. DXA is preferred for several reasons. It provides a lower dose of radiation than QCT, QUS has not been validated over time to monitor for treatment effects, and pDXA has not been validated in men. For all these reasons, DXA is the gold standard for initial evaluation and serial monitoring of both treated and untreated patients. The interval between DXA scans is typically 1 to 2 years,

 although a longer duration may be appropriate, particularly for those on antiresorptive therapy or patients with low risk of fracture. Although BMD is a surrogate marker of bone strength and predictor of fracture, the majority of fractures occur in patients with normal to minimal bone loss (FIGURE 2). Thus, BMD is a component, but not the only element, in understanding and treating bone health.

The treatment of bone health is 3-pronged. The first step is looking at lifestyle modifications. Patients need to be encouraged to reduce alcohol consumption, stop smoking, participate in weight-bearing exercise (in which bones and muscles work against gravity as the feet and legs bear the body’s weight, such as walking, jogging, tai chi, stair climbing, dancing, and tennis), and explore strategies for fall prevention.

The second step is addressing calcium and vitamin D levels and intake. The NOF and the National Academy of Medicine (NAM) recommendations are that men 50 to 70 years consume 1000 mg/day of calcium and men 71 years and older consume 1200 mg/day of calcium. There is no evidence that calcium intake in excess of these amounts confers additional bone strength. On the contrary, intakes above 1200 to 1500 mg/day may increase the risk of developing kidney stones, cardiovascular (CV) disease, and stroke. The scientific literature is highly controversial in this area. There are suggestions that calcium from dietary sources engenders no increase in CV risk. On the other hand, particularly in men, calcium supplements may have a small impact on CV risk.

 Because ADT itself appears to contribute to CV risk, dietary changes may be a better approach than supplement calcium.

This concern is not currently addressed in the AUA guidelines. The average daily dietary calcium intake in adults age 50 and older is 600 to 700 mg/day. Increasing dietary calcium appears to be the first-line approach but clearly requires more education than recommending a simple pill supplement. Vitamin D plays a major role in calcium absorption, bone health, muscle performance, balance, and risk of falling. The NOF recommends an intake of 800 to 1000 international units (IU)/day for adults age 50 and older. The Dietary Reference Intakes recommended by the NAM are slightly more conservative: vitamin D at 600 IU/day until age 70 and 800 IU/day for adults 71 years and older.

The third step comprises pharmacologic treatments. The first step is deciding which patients clearly benefit from therapy. There is uniform acceptance7 that a patient with osteoporosis should receive pharmacologic therapy in addition to steps 1 and 2 above. Patients with a fragility fracture, particularly an asymptomatic vertebral fracture, are also candidates for pharmacologic treatments. The 2 therapies most studied for treatment are denosumab and zoledronic acid. These are the current AUA guideline recommended therapies. The oral bisphosphonate alendronate has seen limited studies in this group of patients. It also has an effect on BMD and bone turnover markers. However, there are no head-to-head studies in regard to equivalence infracture prevention.

The treatment of bone loss associated with ADT is complex. It requires a detailed history and BMD measurement to fully estimate risk of fracture. Treatment with calcium alone is not sufficient, and potential CV risks underscore the need for counseling for calcium intake. High-risk patients require therapy, and the 2 AUA guideline recommended therapies, denosumab and zoledronic acid, are the standard of care.

Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer.

 2005;352(2):154-164. doi: 10.1056/NEJMoa041943.

Smith MR, Boyce SP, Moyneur E, Duh MS, Raut MK, Brandman J. Risk of clinical fracture after gonadotropin-releasing hormone agonist therapy for prostate cancer.

2006;175(1):136-139. doi: 10.1016/S0022-5347(05)00033-9.

Smith MR. Osteoporosis during androgen deprivation therapy for prostate cancer. 

2002;60(3 suppl 1):79-86. doi: 10.1016/S0090-4295(02)01579-0.

Body JJ. Prevention and treatment of side-effects of systemic treatment: bone loss. 

 2010;21(suppl 7):vii180-vii185. doi: 10.1093/annonc/mdq422.

Roux C, Briot K. Imminent fracture risk. 

 2017;28(6):1765-1769. doi: 10.1007/s00198-017-3976-5.

FRAX Fracture Risk Assessment Tool. Centre for Metabolic Bone Diseases, University of Sheffield, UK website. sheffield.ac.uk/FRAX/. Accessed December 14, 2017.

Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis [erratum in Osteoporos Int. 2015;26(7):2045-2047. doi: 10.1007/s00198-015-3037-x]. 

2014;25(10):2359-2381. doi: 10.1007/s00198-014-2794-2.

Doria C, Leali PT, Solla F, Maestretti G, Balsano M, Scarpa RM. Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? a prospective randomized multicenter international study. 

2016;13(3):195-199. doi: 10.11138/ccmbm/2016.13.3.195.

Klotz LH, McNeill IY, Kebabdjian M, Zhang L, Chin JL; Canadian Urology Research Consortium. A phase 3, double-blind, randomized, parallel-group, placebo-controlled study of oral weekly alendronate for the prevention of androgen deprivation bone loss in nonmetastatic prostate cancer: the cancer and osteoporosis research with alendronate and leuprolide (CORAL) study. 

 2013;63(5):927-935. doi: 10.1016/j.eururo.2012.09.007.

Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP diet and health study. 

 2013;173(8):639- 646. doi: 10.1001/jamainternmed.2013.3283.

The use of androgen deprivation therapy in prostate cancer is now a well-established treatment regimen but is associated with an increased risk for bone fracture.

February 2018 | Oncology Live Urologists in Cancer Care®

A Call to Arms in Urology

Urology Practice Succeeds With Transparency, Upfront Payment Model

Maintaining Bone Health During ADT for Prostate Cancer