A recent phase II trial demonstrated that the combination of docetaxel-based chemotherapy and dexamethasone showed significantly high prostate-specific antigen (PSA) responses compared with previous studies in patients with castration-resistant prostate cancer (CRPC).

In the recent single-arm, multi-institutional study, 75 patients with CRPC received 75 mg/m

 of docetaxel and 0.5 mg of dexamethasone orally twice a day throughout the treatment period. The treatment period was planned for 10 cycles, and depending on the observation of PSA test flares, the treatment was continued for at least 4 cycles. The median age was 71 years, and the median PSA level at enrollment was 23.2 ng/mL.

 Eligible patients had histologically confirmed prostate adenocarcinoma, confirmed CRPC, ECOG performance status of 0 to 1, and were receiving either surgical or medical androgen deprivation therapy.

The primary endpoint was PSA response, defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints included safety, PSA test flares, time to PSA test failure, and adherence rate to proto- col treatment (10 cycles). Radiographic progression was not evaluated. The investigators focused on PSA response in order to assess the effectiveness of the treatment with statistical significance, and because of the diagnostic significance of PSA testing. It also made it simpler to compare the study results with those of previous trials.

Patients would be eligible for a dose reduction or cessation of dexamethasone if certain adverse events (AEs) were reported, including gastric ulcer, posterior subcapsular cataract, glaucoma, infection, or any other toxicities requiring dose reduction or cessation as judged by the attending physician.

The results were statistically promising. The PSA response rate was 76.8% (95% CI, 65.1-86.1). Of all evaluable patients, 30 completed the full 10 cycles of chemotherapy (40%). This response rate was significantly higher than the study’s prespecified threshold (30%). Eight patients experienced a PSA test are (10.7%). The median time to PSA failure was 369 days (95% CI, 245-369). The PSA response rate of patients without metastases (16 patients) was 81.3% (95% CI, 54.4- 96.0), and the PSA response rate of patients with metastases (53 patients) was 75.5% (95% CI, 61.7-86.2), showing a notable difference in the parameters of the study.

The most frequently observed AE was hematotoxicity; neutropenia of grade 1/2 or greater was observed in 100% of patients. Other hematological AEs (all grades) were leukopenia (97.3%), lymphopenia (61.3%), and anemia (97.3%). Other common nonhematological AEs (all grades) included fatigue (70.7%), anorexia (46.7%), peripheral sensory neuropathy (57.3%), peripheral motor neuropathy (24%), and alopecia (69.3%).

The investigators concluded that these results demonstrated a novel PSA response in patients who received docetaxel-based chemotherapy combined with low-dose dexamethasone. Most patients tolerated the protocol schedule, despite the often-seen hematotoxicity.

 raised the question as to whether there was significant benefit in the efficacy and safety of docetaxel-based chemotherapy combined with low-dose dexamethasone in patients with CRPC. Further investigation was needed, and so the Japan-Multinational Trial Organization organized the combination phase II trial to accomplish that.

Further research is still needed. This trial had several limitations, including that radiographic progression was not evaluated. There was also a small sample size, and since the study was single-arm, there is no comparator to confirm the responses. The study also had a short follow-up time period, and so there is no way to assess the PSA response in terms of OS.

 However, the response seen in this trial was excellent, and hopefully more research building on these results will likely be the subject of future trials.

One prior study investigating the efficacy and toxicity of low-dose docetaxel combined with dexamethasone found that 65% of evaluable patients had a decrease in their PSA responses >50%.

The study concluded that low-dose docetaxel in combination with dexamethasone is feasible in patients with CRPC. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 elderly patients, due to gastric bleeding in one and to infective endocarditis in the other. Hematological toxicity was less than that seen with standard docetaxel therapy, but it was necessary to monitor patients during the study for severe nonhematological toxicities, particularly in elderly patients.

A previous study from 2004 (TAX 327) compared treatments of docetaxel plus prednisone versus mitoxantrone plus prednisone for patients with advanced prostate cancer. The study randomized 1006 patients with metastatic hormone-refractory prostate cancer to receive 5 mg of prednisone twice daily, and either 12 mg of mitoxantrone per square meter of body-surface area every 3 weeks, 75 mg of docetaxel per square meter every 3 weeks, or 30 mg of docetaxel per square meter weekly for 5 of every 6 weeks. The primary endpoint was over- all survival (OS).

The TAX 327 study demonstrated that when given with prednisone, treatment with docetaxel every 3 weeks led to better OS and improved rates of response in terms of pain, PSA levels, and quality of life, as compared with mitoxantrone plus prednisone. The median OS was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these groups, 32%, 45%, and 48% of patients, respectively, had at least a 50% decrease in their PSA level (

 <.001 for both comparisons with mitoxantrone).

Tanaka N, Nishimura K, Okajima E, et al. The e cacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial. 

 2017;47(3):247-251. doi:10.1093/jjco/hyw193.

Miura N, Tanji N, Yanagihara Y, et al. Low-dose docetaxel combined with dexamethasone is feasible for patients with castration-resistant prostate cancer. Chemotherapy. 2016;61(1):23-31. doi: 10.1159/000440942.

Tannock IF, de Wit R, Berry WR, et al; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.

Articles

A recent phase II trial demonstrated that the combination of docetaxel-based chemotherapy and dexamethasone showed significantly high PSA responses compared with previous studies in patients with CRPC.

Docetaxel Combined With Dexamethasone Shows PSA Response in Patients With CRPC

The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario have jointly updated their guideline for using brachytherapy treatment for patients with newly diagnosed prostate cancer who require or choose active treatment and are not considering, or are not suitable for, active surveillance.

The update provides evidence-based recommendations for different patient risk groups, and it clarifies the most effective forms of brachytherapy for each patient population.

An expert panel of ASCO and Cancer Care Ontario representatives conducted a systematic literature review and identified 5 randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer as evidence for the update. The guideline now covers issues regarding the efficacy of brachytherapy alone compared with EBRT or radical prostatectomy, the efficacy of brachytherapy combined with EBRT, and which isotopes used for low-dose rate (LDR) brachytherapy maximize clinical outcomes when used in patients with newly diagnosed prostate cancer.

“This guideline provides very clear direction about what is now the nonsurgical standard of care for many patients with prostate cancer—brachytherapy either by itself or as part of a combination approach,” said Andrew Loblaw, MD, FRCPC, MSc, a co-chair of the expert panel representing ASCO, in a press release. “Brachytherapy is also more convenient than external beam radiation, and has a much higher chance of curing the disease. However, not every patient should have brachytherapy, and not all treatment centers are experienced in delivering highquality brachytherapy.”

The guideline does note that the recommendation for low-risk patients is unchanged from the initial guideline recommendations, because no new randomized data regarding this specific patient population and treatment were presented or published between 2011 and December 2016. The guideline also now clarifies that for any patient who chooses to undergo brachytherapy, the treatment should be performed at a center that follows strict quality-assurance standards.

The new recommendation for patients with low-risk prostate cancer who require or choose active treatment is that oncologists and other healthcare practitioners should offer either LDR brachytherapy alone, EBRT alone, or radical prostatectomy alone. The guideline qualifies that patients should be counseled in a balanced, objective manner on all their treatment and management options, preferably from multiple disciplines, including surgery, EBRT, and active surveillance.

For patients with intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy (ADT), the guideline now recommends that LDR or high-dose rate (HDR) brachytherapy boost should be offered to eligible patients. For low-intermediate risk prostate cancer, defined as Gleason score 7, prostate-specific antigen (PSA) <10 ng/mL or Gleason score 6, PSA 10 to 20 ng/mL, LDR brachytherapy may be offered as monotherapy. Similarly, eligible patients with high-risk prostate cancer who are receiving EBRT and ADT should be offered LDR or HDR brachytherapy boost.

It was also determined that iodine-125 and palladium-103 are reasonable isotope options for patients who are receiving LDR brachytherapy. The guideline notes, however, that no recommendation can be given against or in favor of using cesium-131 or HDR monotherapy.

The guideline now cautions that there may be increased genitourinary toxicity associated with brachytherapy compared with EBRT alone. The guideline states that it could not be determined whether there is an overall or cause-specific survival advantage for brachytherapy compared with EBRT alone, because none of the trials the panel reviewed were designed or powered to detect a meaningful difference in survival outcomes.

The guideline also adds qualifying statements for patients with prostate cancer who are not candidates for brachytherapy in general. According to the guideline, patients who are ineligible for brachytherapy may include those who have moderate to severe baseline urinary symptoms; have large prostate volume; are generally medically unfit; have had prior transurethral resection of the prostate; and/or take medications with contraindications to radiation treatment.

As an alternative, the guideline states, ADT may be given in neoadjuvant, concurrent, or adjuvant settings at the physician’s discretion. The guideline also notes that neoadjuvant ADT may cytoreduce the prostate volume sufficiently to allow brachytherapy, pointing to a potentially advantageous treatment strategy for certain patients.

Chin J, Rumble RB, Kollmeier M, et al. Brachytherapy for patients with prostate cancer: American Society of Clinical Oncology/Cancer Care Ontario joint guideline update.

 2017; JCO2016720466. doi: 10.1200/JCO.2016.72.0466.

ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer [news release]. Alexandria, VA, and Toronto, Canada: ASCO Communications; March 27, 2017. https://www.asco.org/about-asco/press-center/ news-releases/asco-and-cancer-care-ontario-update-guideline-radiation. Accessed April 18, 2017.

Joseph Chin, MD, FRCSC, a co-chair for the expert panel representing Cancer Care Ontario, added: “For the urologists, who are most often the gatekeepers in terms of first contact with men with prostate cancer, this guideline update provides new information which they can incorporate into patient counseling and treatment decision making. By optimizing treatment selection, which may or may not be brachytherapy for a particular patient, outcomes should ultimately be improved.”

The American Society of Clinical Oncology and Cancer Care Ontario have jointly updated their guideline for using brachytherapy treatment for patients with newly diagnosed prostate cancer who require or choose active treatment and are not considering, or are not suitable for, active surveillance.

Guideline Update Clarifies Role of Brachytherapy for Patients With Newly Diagnosed Prostate Cancer

The American Urological Association (AUA), in collaboration with the Society of Abdominal Radiology (SAR), convened for a Prostate Cancer Disease Focused Panel to conduct a literature review and create consensus statements regarding the role of prostate magnetic resonance imaging (MRI) and MRI-targeted biopsy in patients with a prior negative biopsy. This came as a result of recent improvements in technology and the increasing number of urological practices incorporating prostate MRI into the routine care of select patients with a prior negative biopsy.

There are currently 3 main strategies for targeted MRI in a repeat biopsy: cognitive targeting, performing a biopsy while the patient is in an MRI gantry, and real-time MRI/ultrasound fusionguided prostate biopsy. While many studies demonstrate the usefulness of each procedure, no studies have compared these methods, according to the consensus statement.

Cognitive targeting requires the least technology; it involves estimating the location of the tumor detected on the MRI and transferring the target to a transrectal ultrasound without additional technological guidance. The lack of visual feedback, according to the consensus statement, results in a less accurate and reliable approach, since it largely relies on the expertise of the practitioner. The statement does recognize, however, that cognitive biopsy procedures have shown positive results in the literature the AUA and SAR reviewed.

The second technique, performing a biopsy while the patient is in an MRI gantry, offers the advantage of being the most direct targeting for a repeat biopsy. With this technique, MRI images are taken to confirm placement of the biopsy needle in the target tumor. However, the consensus statement points out that this method is more time-consuming and labor-intensive, and may be uncomfortable for the patient, who must lie in a prone position throughout the procedure.

The real-time MRI/ultrasound fusion-guided prostate biopsy involves a planning session before the procedure, in order to define the boundaries of the prostate and the location of the targeted tumor(s) through an MRI scan. The prostate and target map is then loaded into the fusion biopsy system, and at the time of the biopsy, the MRI data are combined with the transrectal ultrasound, effectively linking the movements of the 2 imaging results so the biopsy is performed under transrectal ultrasound, but using MRI guidance. The consensus statement lauds this approach for its familiar procedures and its relatively shorter duration to perform, but recognizes the possibility of a co-registration error impeding the accuracy of the results.

While the use of advanced technology such as a fusion system or an in-bore biopsy system may be helpful, the superiority of any specific approach has not been established, according to the statement. One approach may be to apply different methods of MRI targeting depending on the characteristics of the tumor. For example, a urologist may use an in-bore or fusion system for tumors that are smaller in length or in a region difficult to access (such as the anterior or apical prostate) while limiting cognitive targeting to other targeted tumors.

Although fusion and in-bore biopsy systems may have value in improving biopsy yield, they have high costs associated with them, according to the guidelines. The consensus statement supports cognitive targeting as a sound approach for the detection of prostate cancer when advanced technologies are not available, and when operators are skilled with imageguided procedures.

The consensus statement advises that practitioners should take at least 2 cores from each MRI-targeted tumor biopsy procedure. It also advises that systematic and MRI-targeted cores be separately labeled, given that currently accepted clinical nomograms are derived from data based on standard systematic biopsy results.

After an initial negative biopsy, there has been an ongoing need to improve strategies for performing repeat biopsies. There is an additional need to improve the diagnostic yield from repeat biopsies, in order to prevent patients from undergoing unnecessary repeat biopsy procedures. While there are options for patients with a prior negative biopsy, if a subsequent biopsy is recommended, using MRI-targeted cores improves the detection of clinically significant disease over a standardized repeat biopsy.

However, several challenges exist in optimally using and assuring quality of prostate MRI scans. There is variation in image quality as well as in the interpretations of radiologists examining the images. There is currently no standardization for image quality, and so even when different centers are using the same equipment, there may not be the same examination quality, leading to false-positive or falsenegative readings.

To date, the implementation of prostate MRI and MRI-targeted biopsy has been concentrated in major academic centers that have developed the necessary radiological expertise to provide accurate MRI interpretations. For prostate MRI to be widely adopted, community radiologists will need to become more trained and experienced, although there is no formal way for radiologists to become certified in prostate MRI interpretation. These consensus statements are designed to provide the first step in moving toward a comprehensive program of diagnostic MRI and MRI-targeted prostate biopsy.

Rosenkrantz AB, Verma S, Choyke P, et al. Prostate magnetic resonance imaging and magnetic imaging targeted biopsy in patients with a prior negative biopsy: a consensus statement by AUA and SAR. 

 2016;196(6):1613-1618. doi: 10.1016/j. juro.2016.06.079.

The American Urological Association, in collaboration with the Society of Abdominal Radiology, convened for a Prostate Cancer Disease Focused Panel to conduct a literature review and create consensus statements regarding the role of prostate magnetic resonance imaging (MRI) and MRI-targeted biopsy in patients with a prior negative biopsy.

AUA Releases Consensus Statements on 3 Main Methods of Prostate MRI, Targeted Biopsy

Over the years, the term “personalized medicine” has become part of the modern day lexicon in healthcare. In fact, has not medicine, in general, always been personalized? It is very rare that we follow the exact same script for every patient condition that we treat. Taken into account are a number of host factors that determine the optimal pathway: patient’s age, body type, allergies, current medicines, comorbid conditions, life expectancy, imaging findings, etc. At that point, we as physicians outline a treatment plan that will hopefully result in the best possible outcome and, most importantly, pair with patient expectations as a result (this latter point is often overlooked by many).

We are entering the era of molecular testing and screening, which is becoming more ubiquitous and does not require a second mortgage to obtain, as well as the ability to perform next generation sequencing (NGS) on tissue. Medicine, especially in cancer management, has entered the “precision” era. Clearly, our understanding of tumor biology has taken us into uncharted territory. We were prophetic in this column years ago that it would be less about the organ of origin and more about identifying particular pathways that result in these rogue tumor cells surviving, escaping the current therapeutic regimen, mutating, and ultimately causing the demise of our patients.

By now, I am sure many of you have read, or at least are aware of, the article published in the 

 last year that examined the incidence of germline mutations in DNA repair genes among men with metastatic prostate cancer.

 In summary, men with metastatic prostate cancer had a significantly higher incidence of germline mutations in DNA repair genes, including 

, compared with men with localized prostate cancer than what was anticipated from prior data sets. In addition, the frequency of these mutations was not significantly different in men with or without a family history of prostate cancer. This finding, combined with the fact that the use of poly (ADP-ribose) polymerase inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) who were identified by NGS to harbor mutations and deletions in DNA repair genes, heavily pretreated with androgen axis modulators (abiraterone acetate or enzalutamide) and/or taxane chemotherapy (docetaxel or cabazitaxel), showed a significant tumor response.

The implications here are significant. For our patients with mCRPC, the addition of another mechanistically unique agent to our growing armamentarium of oncolytics, which now includes autologous immunotherapy, androgen synthesis inhibitors, androgen signaling/receptor inhibitors, radiopharmaceuticals and taxane-based chemotherapies, provides another option as we try and stay ahead of these mutational changes. As we are all well aware, the combination of agents, and most importantly, the ability to monitor therapies without tissue biopsy, remains a significant challenge.

But for the practicing urologist, even if you are not going to be actively engaged in treating and managing patients with mCRPC, understanding and appreciating these mutations is critical, especially when it comes to family counseling. In years past, we only concentrated on a family history of first degree relatives with prostate cancer and recommended early PSA screening for these patients. Now, we should also be focusing on obtaining detailed family histories for other heritable tumor types, including breast, ovarian, pancreatic, and others. What is going to be our role in obtaining molecular screening tests now being offered by many vendors across the United States? What would be the timing? Is it for all men that we discover a significant family history, or is it only in men with advanced and aggressive disease? And if we do adopt this philosophy of early testing, does the typical urology office have the bandwidth to manage the fallout and act on the data, specifically in family counseling?

These are all very important issues that as a specialty, we need to be addressing proactively if we want to be viewed as the experts in prostate cancer. Educating our patients and colleagues is a mandate that we should all embrace in order to stay cogent in this rapidly evolving area.

Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. 

 2016;375(5):443-453. doi: 10.1056/NEJMoa1603144.

Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. 

 2015;373(18):1697-1708. doi: 10.1056/NEJMoa1506859.

Raoul S. Concepcion, MD, discusses the new era of molecular testing and screening and how it has impacted the field of prostate cancer thus far. 

Precision Medicine Circa 2017

Michael Barkoukis, MD, and Tim Sidor, MD, started SouthWest Urology of Cleveland, OH, in 1982 from scratch with $100,000 in borrowed capital, a box of pens, and a copy machine. Both men grew up on the west side of Cleveland, and both ended up at Case Western Reserve University in the same medical school class. Both aspiring urologists were accepted into a residency program at the University Hospitals in Cleveland, and as their training progressed, they decided to begin a urology practice together. “I had looked at several other jobs in the Cleveland area, but I felt that there was a niche on the southwest side of Cleveland,” Barkoukis said.

From those humble beginnings 35 years ago, the successful practice has grown to include a main office in Middleburg Heights, 5 additional locations, a team of 9 urologists, and a support staff of 60 full- and part-time employees, including 20 surgery center staffers.

The greater Cleveland area in Cuyahoga County is dominated by hospital groups that offer oncology treatment, among them the Cleveland Clinic and University Hospitals, but SouthWest has become the largest independent urology practice. “We’ve tried to differentiate ourselves from the larger academic centers, and we would like to continue to do that,” said Lawrence A. Gervasi, MD, CPI, medical director of clinical research and director of SouthWest’s advanced prostate cancer clinic.

SouthWest is proud of its level of integrated service. The practice has urologists who specialize in roboticassisted surgery, erectile dysfunction, the diagnosis and treatment of advanced prostate cancer, and women’s urologic health. Their diagnostics department has imaging capabilities that include computed tomography scans and state-ofthe-art magnetic resonance imaging (MRI) fusion biopsies. SouthWest also has an in-office drug dispensary. The physicians follow a model that encourages physicians to work as team players, rather than trying to do everything themselves, according to Claudio Zanin, MBA, CEO of SouthWest Urology.

“I’ve seen a lot of different compensation models that focus more on productivity—and the more you work, the more you make. Our model lends itself to quality, where a doctor sees a patient, explains the situation, and refers the patient to someone who is really good at doing the procedure,” Zanin said. Because the practice offers all aspects of urological care, a collaborative culture fostered by the integrated model is crucial to taking care of patients, he added.

The comprehensive, integrated care at SouthWest helps the practice to compete with the diversity of offerings at hospital systems as Cleveland Clinic, said Barkoukis, who is president of SouthWest and clinical professor of Urology at Case Western Reserve University. “A lot of our patients like the idea that they can pull into a local neighborhood parking lot, come into the building and see their doctor, have their x-ray performed in the same building, and have their surgery.”

However, when it comes to systemic chemotherapy, the practice does not have a medical oncologist to manage patients on this treatment, so patients must be referred elsewhere. To resolve this, the practice is considering hiring a medical oncologist to bring that area of care to their practice. The only oncology service they do not have avaialble is pediatric oncology.

For the last 10 years, SouthWest’s main office has been in Middleburg Heights, which has its outpatient ambulatory surgery center and imaging centers on the first floor, offices on the second floor, and the research center on the third floor. They also have 5 satellite offices, 1 in Medina, OH, 1 in Brook Park, OH, 1 at St. Vincent Charity Medical Center in Cleveland, and another at Marymount Hospital in Garfield Heights, OH.

The company is able to obtain experimental treatments for patients through a collaboration with a company that manages clinical trials. “We have a unique situation where we work with a company that’s called Clinical Research Solutions. They supply the clinical research coordinators, and I do the physician’s part, recruiting patients for trials,” said Gervasi. A few years ago, when SouthWest first decided to do clinical trials, they realized that outside expertise would be critical to managing the program effectively.

The challenges for an independent practice running studies can pile up quickly, practice members said. Revenue for studies is not booked consistently, and funding may have to come from the practice itself to cover interim costs of staffing and resources. If a practice should make a mistake in their administration of a trial, they may never get paid or be able to cover all the costs involved in running a study.

“You really need to know what you need to do in terms of all the paperwork, and there are a lot of things that need to be done to run a clinical trial, and if you don’t do them right, you’re not going to get more studies,” Zanin said. The way that the clinical trials program is set up now, there is very little overhead cost, the physicians are in touch with Clinical Research Solutions every day, and SouthWest is satisfied with the way the program is running.

SouthWest is satisfied with the way the program is running. SouthWest has what Gervasi described as a very active clinical trials program. He said the practice is currently recruiting patients for 12 to 14 clinical trials. A number of them are for prostate cancer, but there are also trials in benign prostatic hyperplasia and overactive bladder. “What’s helpful is that this also extends a lot of opportunities to patients who may not be candidates for FDA-approved drugs for prostate cancer because their disease is not advanced enough, so these are people we’ll consider for a trial so they can be treated with some kind of medication rather than waiting until they have metastatic disease,” Gervasi said.

The trials with which they are currently involved are intended to show how well oral drugs are going to work for patients with early stage prostate cancer. “We just got approved for a trial using one of the PARP inhibitors for prostate cancer, so I think that’s another exciting new area for a drug class that’s been approved for ovarian cancer, and now it’s being looked at in the area of prostate cancer,” Gervasi said.

SouthWest’s prostate cancer clinic began as a clinic for patients with prostate cancer who received treatments that affected their bone health. Doctors in the clinic would make sure that patients were taking their medications and getting their vitamins, scans, and imaging. Over time, the program evolved into an advanced prostate cancer clinic.

As more medications and treatments become available, SouthWest hopes to add these to its drug armamentarium in order to retain the patients under its care and attract new ones. “What happens is when people get to the point where they have advanced prostate cancer, they’ve already been at our practice for possibly many years, so they’re very comfortable with us; they’re very satisfied with the care and they don’t like to leave the practice, so that’s why it’s nice to be able to offer these treatments right here at our practice where they feel comfortable,” Gervasi adds.

The broader range of therapies has made the treatment of prostate cancer more optimistic, he added. “There are all these new therapies that were not available about 6 years ago; there’s also drugs for bone health that we give, and all these are available to the patients, which really gives them more hope than they had just a few years ago. All of these improve overall survival, so patients are happy to hear this, and it’s a very good atmosphere for patients with advanced prostate cancer,” Gervasi said.

SouthWest recently started offering MRI fusion biopsies for the patients, as other large practices are doing. MRI of the prostate and MRI fusion biopsies are newer procedures that help determine whether a patient would be placed on active surveillance or not. These tests combined with genomic testing are helpful to discern how aggressive a patient’s prostate cancer is and to determine how aggressive the therapy should be.

Just a few years ago, there was a lot of debate within the practice a few years ago about whether they should utilize this new technology. According to Zanin, the issue was that they would not be compensated for MRI fusion biopsies, and the cost was over $100,000 for the equipment. “You have to look at things from a business standpoint, because no money, no mission,” Zanin said. Although the practice could not bill payers for MRI fusion biopsies, patients were asking about the procedure, and finally everyone in the practice decided they needed to make these tests available. “We found a way around things to do it at the hospital, which is good, but the next step is to bring it under our domain,” Zanin said.

The need for high-quality prostate clinics has been on the rise lately, and this gives the partners at SouthWest the sense that they are well positioned for this trend. “What’s been documented across the country, amid the controversy about PSA screening, is that in general fewer of the primary care physicians are screening, so we have seen the number of biopsies and the number of people being diagnosed with prostate cancer decreasing over the last few years, and that also corresponds to an increase in incidence of higher-grade and higher-stage prostate cancer,” Gervasi said.

The goal for SouthWest is to continue to grow their practice, but they must compete with Cleveland Clinic and University Hospitals for employee candidates. It’s difficult to recruit urologists because hospitals are able to offer higher salaries, and because more urologists are retiring than are graduating. “It just seems that the old-school urologists and the new-school urologists may have different types of mindsets. The new urologists coming out of school may be looking to go toward the [hospital] system to get more security and not be on call so much,” Zanin says.

SouthWest’s partners have discussed growing by merging with other private practices so they can continue to provide integrated, high-quality, efficient care to their patients. Zanin believes that they need to recruit more urologists or partner with other independent practices. Until now, urologists have come to the practice 1 at a time, instead of through mergers. “Part of what makes this group successful is that we’ve made a culture that allows us to continue to grow, and now we need to grow more,” Zanin said.

Despite the recruitment challenges, SouthWest has a lot to offer a urologist, including autonomy and the possibility to work up to a partner position. “Because of the bricks and mortar, the physicians, the salaries they get paid, and the size of an institution, the cost of delivering care in [hospital] systems is much higher than the cost of delivering care in an independent practice like ours,” Barkoukis said. “If you can get the same quality care, and you can get it done efficiently and easily by a group like ours at a lower price, and as the patient becomes a consumer with higher deductibles and health savings accounts, they’re going to be looking for treatment that can be done cheaper as long as it’s comparable, especially if it can be done in their own backyard.”

Michael Barkoukis, MD, and Tim Sidor, MD, started SouthWest Urology of Cleveland, OH, in 1982 from scratch with $100,000 in borrowed capital, a box of pens, and a copy machine.

SouthWest Urology Uses Quality-Focused Integrated Care Mode

In recent years, immunotherapy advancements have generated much excitement in oncology, and that is no different in the urologic arena. We have been reporting on these developments as they come up, and so far, we have seen progress this year for understanding, developing, and gaining regulatory approval for immunotherapies in urologic cancers.

In our cover story for this issue, “More Therapies Targeting PD-1/PD-L1 Pathway in Bladder Cancer Emerge,” we review the latest information given on several of these treatments being developed for urothelial cancers, including atezolizumab (Tecentriq), pembrolizumab (Keytruda), nivolumab (Opdivo), avelumab (Bavencio), and durvalumab (Imfinzi).

Atezolizumab was granted accelerated approval by the FDA in May 2016 as a treatment for patients with locally advanced or metastatic urothelial carcinoma (UC). Although results from the IMvigor 210 study showed that patients treated with atezolizumab experienced clinically meaningful benefits, recently it was announced that the IMvigor 211 trial did not meet its primary endpoint of overall survival compared to chemotherapy for patients with metastatic UC.

Pembrolizumab has shown great promise when combined with chemotherapy in patients with previously treated metastatic UC, according to preliminary data from an ongoing trial led by Primo N. Lara Jr, MD, a urologic oncologist at the University of California, Davis. The data from this trial are described in detail in our conference coverage section of this issue.

Avelumab is also showing promising efficacy and safety in treating patients with metastatic UC. In an exciting development, avelumab was granted accelerated approval by the FDA in early May, 2017. Avelumab is now approved for patients with mUC who have disease progression following platinum-containing chemotherapy.

In February, the FDA granted an accelerated approval to nivolumab monotherapy as a treatment for patients with locally advanced unresectable or metastatic UC following progression on a platinumcontaining therapy. However, nivolumab is also doing well in recent combination therapy trials. In combination with ipilimumab (Yervoy), patients with metastatic UC saw a benefit after having no response to single-agent nivolumab. This tells us a great deal, and will help design more robust and effective combination therapies moving forward.

Durvalumab also has been demonstrating compelling clinical activity not only for patients with locally advanced or metastatic UC, but also in combination with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in prostate cancer. Durvalumab was recently granted accelerated approval by the FDA for patients with metastatic or locally advanced UC who have disease progression during or following platinum-containing chemotherapy. Could durvalumab be the “dark horse” in this race for developing immunotherapies for a wider net of urologic cancers?

We will certainly continue to report on durvalumab’s development moving forward, as well as all the other immunotherapies as they progress toward clinical utility.

In recent years, immunotherapy advancements have generated much excitement in oncology, and that is no different in the urologic arena.

May 2017 | Oncology Live Urologists in Cancer Care®

Docetaxel Combined With Dexamethasone Shows PSA Response in Patients With CRPC

Guideline Update Clarifies Role of Brachytherapy for Patients With Newly Diagnosed Prostate Cancer

AUA Releases Consensus Statements on 3 Main Methods of Prostate MRI, Targeted Biopsy

Precision Medicine Circa 2017

SouthWest Urology Uses Quality-Focused Integrated Care Mode

Dedicated Efforts Are Paying Off in Immunotherapy