Urologic practices, both small and large, find themselves at a crossroads given the current healthcare landscape. Pressure from many sides, especially from regulatory and clinical challenges, places today’s urologic practice in a precarious position. The health reform landscape, which emphasizes the shift to a value-driven versus volume-driven model of care, poses unique challenges that urology practices have never faced before. The explosion of new therapeutics developed for the advanced prostate cancer setting can challenge urology practices to provide their patients with the latest and most optimal care. In addition, with hospital care hovering around 3 to 6 times the cost of outpatient care, many urology practices are finding that they cannot just sit back and merely practice medicine.

Founded in 1922 by Charles Devine, Sr, MD, the Urology of Virginia practice is instilled with a pioneering spirit demonstrated throughout its history. In 1952, his son, Charles Devine Jr, MD, joined the practice, followed by his other son, Patrick Devine, MD, in 1957. The elder Devine eventually became a world renowned specialist in male pelvic reconstructive surgery. By chance, the presence of a plastic surgeon during one of his surgeries sparked a collaborative effort that resulted in countless innovations in urologic procedures.

: You opened the Paul F. Schellhammer Cancer Center in 2012?

The Devines established a urological residency in 1965 at Norfolk General Hospital. They were also instrumental in the organization and establishment of Eastern Virginia Medical School where the current urology residency resides. 

spoke with Michael Fabrizio, MD, CEO of Urology of Virginia practice, as well as Dana Adams, COO, to gain their perspective on the challenges that urology practices face today.

: Yes, the cancer center was dedicated in 2012 to Paul F. Schellhammer, MD, senior partner at Urology of Virginia. Dr. Schellhammer has been a physician with the practice since 1974, and a faculty member of Eastern Virginia Medical School since 1978. He served as chair of the EVMS Department of Urology Healthcare Professionals Network http://bit.ly/28kxU5z from 1989-2000.

What kind of services do you provide your patients?

We now have 32 urologists as well as physician assistants, nurse practitioners, and nearly 300 employees.

: We offer an infusion center to administer immunotherapy. We offer a specialty pharmacy to provide patients with access to oral oncolytic medications. We now have a state-of-the-art ambulatory surgery center, which is opening up in June on the second floor. The ambulatory surgery center was created through a partnership with Chesapeake Regional Medical Center, a local hospital system, to provide convenient and easily accessible surgical care. On our first floor, patients will find cutting edge imaging services offered through a private company called MRI & CT Diagnostics. That company offers the newest 3T magnet 64-slice CT scanner and bone scan imaging for our patients. Because the services are not hospital-owned, they are the lowest cost option in Hampton Roads and in the entire geographic area.

Virginia is a Certificate of Need state. How does this affect your practice?

Moving onto bladder cancer, what developments have you excited?

How about renal cell carcinoma? What’s new and exciting in this disease?

The American Urological Association meeting just ended. Did you attend and what was exciting there?

MF: A state with this designation requires approval by the planning district for any proposed acquisitions, expansions, or creation of facilities. Of course, all the hospitals in the state comply with this certification. However, very few independent physicians are able to obtain a certificate of need. But, as you are well aware and as you have probably seen in the media throughout this year, hospital-based care is exceptionally expensive. In-patient hospital care is typically three-fold higher than care provided in an outpatient setting. In the state of Virginia, our costs are kept artificially high by the fact that there’s a certificate- of-need issue. We’re hoping that that will change in the next year to come. We could offer more comprehensive care in our center, like providing our own intensity-modulated radiation therapy (IMRT) services, except we are in a Certificate of Need state. A lot of other urology practices in the country provide IMRT as another treatment therapy within their practice. But, unfortunately, with our state regulations we can’t have that.

: In May, the FDA approved a therapy for patients with more advanced bladder cancer called atezolizumab (Tecentriq). Tecentriq is a PD-L1 inhibitor, which is indicated for patients with locally advanced or metastatic urothelial carcinoma (mUC), or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery. I expect to see more PD-1/ PD-L1 inhibitors gaining regulatory approval in the next months to years. It’s the newest therapy in the last 30 years in bladder cancer, so we’re excited to be able to offer this to our patients.

: I think an exciting development is that we can take care of renal cell carcinomas that are localized in a much more minimally invasive fashion, due to the advent of robotic partial nephrectomy. But there are exciting therapies for patients to receive in the neoadjuvant setting prior to treatment or post-treatment, and several therapies that are available orally for these patients.

: Overall, there was a lot of excitement around potential therapies for advanced prostate cancer, especially in the M0 or M1 space. But I think what’s really interesting is how we are managing patients with low-volume prostate cancer. That is a field that has really been revolutionized over the last couple years with respect to active surveillance, and I think we are getting a better handle on which patients we can place in this category as opposed to treat.

In addition, we can use genetic markers now. There is a variety of genetic markers that can actually help us delineate which patients may be at risk to develop progressive disease or we can actually use magnetic resonance imaging (MRI) in a more effective fashion to identify lesions that may be more lethal.

What would your recommendations be to a midsize practice or even a small practice about financial viability?

The information provided by the Canary Foundation, especially in early disease detection, is important. The Canary Prostate Program, which includes the Prostate Cancer Active Surveillance Study (PASS), is a large tissue microarray biomarker project involving innovative imaging techniques. It is designed to address urgent, high-impact challenges in prostate cancer.

: I would say the most important ability for the practice is to continue recruiting physicians. There is an overall shortage of urologists and that is only expected to continue. Recruiting is something to focus on for the future. Second, practices now need to keep one step ahead of all the government regulations such as HIPAA, upcoming changes to Merit-Based Incentive Payment System (MIPS), and different payment methodologies. Keeping abreast of those changes and continuing to change as regulations change is paramount. Third, new treatment options and surgical treatments should be incorporated into the practice that can be offered to patients. I think those are the three big things to ensure viability moving forward.

Articles

Michael Fabrizio, MD, and Dana Adams, COO, provide their perspective on the challenges that urology practices face today.

With Its Long History and Pioneering Spirit, Urology of Virginia Faces a Changing Landscape

Over the past few months, an alarming number of events have surfaced that we, as providers of oncologic urology care, should take notice. For starters, January 1, 2017 will be upon us very quickly. And what you may ask is the significance of that date for physicians?

That is when CMS, outlined in the Medicare Access and CHIP Reauthorization Act (MACRA) passed in 2015, will begin keeping scorecards on all of us in the transition to value/ performance based medicine. If you have been trying to keep up and stay abreast of this legislation that is succinctly distilled in a mere 900+ page document, there are many unknowns and questions that await us. But again, make no mistake, this will be upon us quite soon.

To compound our potential woes and challenges, potentially this fall, 75% of the country will be partaking in the Medicare Part B 5-year pilot program to test a new delivery for prescribed drugs to determine if this will result in better patient outcomes (see my prior missive in the last publication).

However, how does one measure patient outcomes when none of the endpoints of this “experiment” include any sort of quality metrics? It’s the government….I can’t make this up! The government wants to spend less money and will go through very circuitous paths to achieve this goal. It touts this as budget neutrality. See Tables 1 and 2, courtesy of Deepak Kapoor, MD, in New York, chairman of LUGPA Health Policy.

 As you can see, in order to stay budget neutral, the cuts with the biggest downside will be for the most part agents we use for management of advancing prostate cancer, offset by many non-oncolytic drugs. For the ever increasing number of groups that have taken on this essential role of providing the continuum of care for prostate cancer, this will be devastating for our patients.

In another interesting ruling, it was announced by Caremark CVS and Express Scripts, that beginning January 1, 2017, they will consider the physician’s in-office dispensing (IOD) pharmacies that many specialties have set up, including urology, to be out of network. Although this ruling is not as harmful across the board for our specialty, it does impact the business model of integrated care that many of us have built.

 This is analogous to some employer (primarily hospital systems) insurance plans that mandate use of their own facilities for certain out-patient services, rather than allowing the patient go to a more efficient, cost-effective center of excellence, in order to drive and maintain their profits. The results are the same: more expensive healthcare at the expense of patients and physicians.

Finally, it was recently brought to my attention that the government is looking into contributions by the pharmaceutical industry that subsidize patient assistance foundations (

http://www.bloomberg.com/news/articles/2016-05-19/the-real-reason-big-pharma-wants-to-help-pay-for-your-prescription

As those of you that have set up advanced prostate cancer centers for the management of our castration-resistant prostate cancer (CRPC) patients, these entities provide often times much needed financial assistance for many of our patients, many of whom are on fixed incomes, have no secondary coverage or, at times, no coverage whatsoever. With the explosion of new therapies over the past 6 years, it is very likely that a patient will receive a minimum of at least 2 to 3 of these agents before succumbing to CRPC. At a price of five to six figures per drug, many people would be forced to go without treatment or be thrust into financial distress if there were not funds available to help them with co-pays. It has been documented that patients with cancer are about 2.5 times more likely to declare bankruptcy than non-cancer patients, who may in fact have an increased mortality rate (

https://www.fredhutch.org/en/ news/center-news/2016/01/cancer-bankruptcy-death-studyfinancial- toxicity.html

As we move into a more advanced role in the management of all GU malignancies (and possibly embrace the oncology care model as outlined by the Center of Medicare and Medicaid Innovation (CMMI), that may have us assume some element of financial risk), it is imperative that we track, monitor and be proactive in fighting some of these changes in order to protect our patients and our specialty. Otherwise, all the great therapies recently brought to market, with many more on the horizon, that have extended survival will all be for naught.

Over the past few months, an alarming number of events have surfaced that we, as providers of oncologic urology care, should take notice.

Troubles Ahead

During the annual American Urological Association (AUA) meeting leaders in urology presented groundbreaking research, new clinical guidelines, and the latest advances in urologic medicine. Our coverage this month highlights the discrepancies found in the Prostate, Lung, Colorectal, and Ovary (PLCO) trial. The PLCO data were instrumental in the recommendation made by the US Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening.

Investigators found a high rate of PSA testing in the control arm of the study, making any meaningful comparisons with the intervention group impossible. The trial was launched in 1993 and involved 77,000 men with an average risk of prostate cancer who were randomized to receive an annual PSA screening for 6 years and a digital rectal examination for 4 years or no screening tests. The USPSTF made its recommendation based on the PLCO data. The discrepancy will likely have a far-reaching effect on policy, so stay tuned.

In other news during the conference, the utility of the Decipher Genomic Classifier (GC) in prostate cancer was further elucidated. Two studies we highlight this month demonstrate its growing importance. In a study by Trock et al, the use of the GC in patients after they undergo radical prostatectomy (RP) can inform how further treatment should progress. The findings could affect the treatment algorithm in men who are at high to very high risk after RP by stratifying risk associated with prostate cancer-specific mortality. The GC showed a 3-fold increase in risk of death, even after adjusting for men at very high risk of prostate cancer.

In another study, the GC assay was able to predict which patients might respond to hormonal therapy, resulting in the discovery and validation of an adjuvant androgen-deprivation therapy resistance signature. This signature could potentially identify patients who may not respond well to androgen-deprivation therapy. Most importantly, it could prevent certain patients from undergoing needless morbidity and inform clinicians to try different systemic approaches. A one-size-fits-all algorithm does not always work out for the best.

There were many sessions to attend, presentations to view, and colleagues to network with during the AUA conference, but I’d like to call your attention to our OncLive® Peer Exchange this month, “Clinical Challenges in Genitourinary Cancers,” which was moderated by our editor-in-chief, Raoul Concepcion, MD. The panelists met prior to the AUA meeting to discuss the challenges that oncologists and urologists face in the genitourinary (GU) arena.

Despite the progress made in the GU field, as our understanding of the underlying biology of prostate and bladder cancer improves, and treatment protocols are refined, there still remain many scenarios in which clear cut answers are not easily identified. The panelists, Michael Cookson, MD, of the University of Oklahoma; Daniel Petrylak, MD, of Yale Comprehensive Cancer Center; David Quinn, MD, PhD, of the Keck School of Medicine at the University of Southern California; and Neal D. Shore, MD, of the Carolina Urologic Research Center, discuss 4 cases to highlight important clinical points and considerations in advanced prostate and bladder cancer. In particular, the panelists explored the emerging role of immunotherapy in bladder cancer, androgen receptor splice-variant 7 in prostate cancer, and cases involving both muscle- and non-muscle invasive bladder cancer.

These stories and more can be found in the June issue of 

During the annual American Urological
Association meeting leaders in
urology presented groundbreaking research,
new clinical guidelines, and the latest advances
in urologic medicine.

PSA Recommendations Challenged After Analysis of PLCO Trial Data

Although androgen deprivation therapy (ADT) has a survival benefit for patients with high-risk and locally advanced prostate cancer, it is associated with substantial safety concerns, and mixed data exist regarding whether ADT causes clinically significant depression. A new population-based study published in the 

 sought to explore this possible association.

Using the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database from 1992 to 2006, researchers identified a total of 78,552 men aged ≥65 years with stage I, II, or III prostate cancer, of whom 33,882 (43%) received ADT within 6 months of diagnosis. Patients with a psychiatric diagnosis in the prior year were excluded.

Patients were categorized as receiving ADT (ADT+) if ADT was the primary therapy or if ADT was given alongside radical prostatectomy (RP) or radiation therapy (RT) before t0. Patients were categorized as not receiving ADT (ADT—) if ADT was not started from diagnosis through the follow-up period of 36 months after diagnosis. Primary treatment was defined as RP with or without ADT, RT with or without ADT, or ADT alone if initiated before t0 as identified through SEER-Medicare claims files, as previously described. To summarize, the ADT+ cohort was older at diagnosis, had more comorbidities, had shorter life expectancies, and had more high-grade disease (all 

The association between pharmacologic ADT and diagnosis of depression (primary endpoint) or receipt of psychiatric treatment (secondary endpoint) was analyzed using Cox proportional hazards regression. An additional secondary analysis explored the association between duration of ADT and the diagnosis of depression or receipt of psychiatric treatment.

Adjusted Cox analyses demonstrated a 23% increased risk for depression (adjusted hazard ratio [AHR], 1.23; 95% CI, 1.15-1.31) and a 29% increased risk for inpatient psychiatric treatment (AHR, 1.29; 95% CI, 1.17-1.41) among patients receiving ADT, and a nonsignificant 7% increased risk of outpatient psychiatric treatment (AHR, 1.07; 95% CI, 0.97-1.17).

All 3 of these parameters demonstrated a significantly increased risk with duration of ADT. For example, the risk of depression rose from 12% with ≤6 months of treatment, to 26% with 7 to 11 months of treatment, to 37% with ≥12 months of treatment.

“We know that patients on hormone therapy often experience decreased sexual function, weight gain and have less energy—many factors that could lead to depression. After taking a deeper look, we discovered a significant association between men being treated with ADT for prostate cancer and depression,” said senior author Paul Nguyen, MD, of Brigham and Women's Hospital, in a statement.

The ADT+ cohort was stratified by duration of therapy, defined as ≤6, 7 to 11, and ≥ 12 months. The cumulative incidence of depression increased by strata, from 6.1% to 7.6% to 8.0% with ≤6, 7 to 11, and ≥12 months of ADT, respectively, compared with an incidence of 5.2% in the ADT— cohort (

 < .001). The incidence of inpatient psychiatric treatment increased by strata, from 2.4% to 3.0% to 3.3%, respectively, compared with 1.9% in the ADT— cohort (

Nguyen added that the findings call for greater awareness of this under-recognized problem not only among patients, but also for clinicians, who need to be aware of the risk in order to recognize signs of depression and refer their patients to appropriate care.

Study authors wrote that these findings add to accumulating evidence around the major adverse event profile associated with ADT, and that the risk of psychiatric illness should be noted as a potential side effect when discussing ADT with patients. The possible adverse event also should be factored in when weighing the benefits and harms of ADT use in older men with intermediate-risk disease.

One study limitation noted by the researchers is that use of Medicare SEER data limited the scope to men aged ≥66 years at diagnosis, and thus, the results may not be applicable to younger men. Additionally, the relationship between depression and ADT treatment may be confounded by the fact that patients were older and had more comorbidity.

The researchers encouraged future studies focusing on interventions that could successfully reduce this risk and to examine whether particular subpopulations are at a higher risk, such as patients with a history of depression.

In the current study, older age, being unmarried, and having more comorbidity were associated with increased depression and psychiatric treatment. Although patients with recent psychiatric disease were excluded from the current study, other work has identified increased rates of depression among similar patients. These populations may be appropriate to target for early-depression screening or intervention after ADT initiation.

Dinh KT, Reznor G, Muralidhar V, et al. Association of androgen deprivation therapy with depression in localized prostate cancer [published online April 11, 2016].

National Comprehensive Cancer Network. (2016). NCCN guidelines, version 2.2016: Prostate cancer. 

Although androgen deprivation therapy has a survival benefit for patients with high-risk and locally advanced prostate cancer, it is associated with substantial safety concerns, and mixed data exist regarding whether it causes clinically significant depression.

ADT Increases Risk for Depression in Elderly Men With Localized Prostate Cancer

A clinical dilemma that urologists face after prostate cancer patients undergo radical prostatectomy (RP), and whose pathology indicates aggressive characteristics such as high-stage or high Gleason score, is how further treatment should progress. The time course to prostate cancer specific mortality (PCSM) is highly variable for men with high risk after RP, and a substantial proportion of men will die of other causes. Accurately stratifying risk of PCSM may allow more appropriate therapy decisions.

Although these men are at a higher risk of death, most of them will be cured by surgery. Clinicians in general would prefer to avoid additional treatment after RP. Results from a study using the Decipher Prostate Cancer Classifier noted that its use added very strong data about the likelihood of dying within 10 years.

The findings could inform the treatment algorithm in men who are high to very high risk after RP by stratifying risk associated with PCSM. The genomic classifier showed a three-fold increase in risk of death even for adjusting for very high risk men, said lead author Bruce J. Trock, PhD, Director, Division of Epidemiology, Professor of Urology, Epidemiology, Oncology, and Environmental Health Services of the Brady Urological Institute, Johns Hopkins University, who presented the results during the 2016 American Urologic Association Annual Meeting.

“Urologists who treat men with adverse pathology or men with positive margins are trying to decide if they are candidates for adjuvant therapy. The other option is waiting until recurrence and giving these patients salvage therapy,” said Trock. The genomic classifier could also be considered for use in men at the time of biochemical recurrence. The Decipher Prostate Cancer Classifier evaluates 22 genomic markers across multiple biological pathways implicated in prostate cancer, to predict the probability of metastasis postprostatectomy.

“The patients who are at very high risk are probably the patients who will have the greatest utility and derive the most benefit,” said Trock. “Men with lower risk are probably going to be cured with surgery. The genomic classifier will identify the patients who have a rapid, aggressive progression.”

Trock and colleagues investigated 511 men with adverse pathologic features (pT3N0/N1, positive margins, or RP Gleason score ≥7) who underwent RP from 1988 — 2010 at three institutions (Mayo, Johns Hopkins, Cleveland Clinic). The primary endpoint was PCSM within 10 years of RP (PCSM10). Men with less than 10 years follow-up were excluded and men who died of prostate cancer after 10 years were censored. Median follow-up was 13.0 years in censored patients and 6.0 years in men with PCSM10. Among all men, a high GC score increased PCSM10 risk nearly 4-fold, HR=3.87 (

 < .0001). Among men with BCR2 or MET after RP, high GC increased PCSM10 risk over 2 — 3 fold (

= .0007 and 0.005, respectively), and area under the curve of 0.743 and 0.671. For both BCR2 and MET the GC was the only significant predictor besides RP Gleason 8 — 10.

When researchers adjusted for clinical variables such as prostate-specific antigen and stage and grade, or using the validated Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) nomogram, a high GC score still resulted in a 3- to 4-fold higher risk of dying than men with a lower score. A patient’s CAPRA-S scores are based on clinical risk factors such as presurgical PSA score, Gleason score, area around the prostate affected by cancer, and lymph node involvement.

“If we looked at categories within CAPRA-S, that is, men who were rated as low risk for death with CAPRA-S and men with a high score in GC had a 25% chance of dying within 10 years even though their CAPRA-S score was low risk. For men with high risk of CAPRA-S, if their GC was low, they only had an 18% chance of dying, whereas if they had a high GC score, their risk of dying was 56%.” Men at high risk by CAPRA-S and the GC “are candidates for clinical trials that are investigating treatments, such as enzalutamide, abiraterone, or docetaxel, that are moving into earlier settings in the metastatic setting,” added Trock.

Trock believes the patients at very high risk will benefit the most from these findings. “Men with lower risk are probably going to be cured with surgery, but this will help identify patients who would have a rapid, aggressive progression. In men with a rapid biochemical recurrence but a low value of GC, they had a low risk of dying from prostate cancer within 10 years.”

Karnes RJ, Ross A, Schaeffer E, et al. Validation of a genomic risk classifier to predict prostate cancer death in high risk patients. Presented at: 2016 American Urological Association Annual Meeting; May 6-10, 2016; San Diego, CA. Abstract MP07-01.

Results from a study using the Decipher Prostate Cancer Classifier noted that its use added very strong data about the likelihood of patients with prostate cancer dying within 10 years.

June 2016 | Oncology Live Urologists in Cancer Care®

With Its Long History and Pioneering Spirit, Urology of Virginia Faces a Changing Landscape

Troubles Ahead

PSA Recommendations Challenged After Analysis of PLCO Trial Data

ADT Increases Risk for Depression in Elderly Men With Localized Prostate Cancer

High Genomic Classifier Score Increases Risk of Dying From Prostate Cancer