Palliative care generally refers to patient and family-centered care that optimizes quality of life by anticipating, preventing, and alleviating suffering across the duration of a patient’s illness. Historically, palliative care referred to treatment available to patients at the end of life who were enrolled in hospice. More recently, palliative care has become available to seriously ill patients regardless of their prognosis. In addition, its meaning has evolved to encompass comprehensive care that may be provided along with disease-specific, life-prolonging treatment.

In the 10 years since the establishment of The National Consensus Project for Quality Palliative Care, a program established to create clinical practice guidelines that improve the quality of palliative care in the United States, the number of hospice programs has increased by 56.5% and non-hospice palliative care programs have increased by 148% in hospitals with over 50 beds.

 In 2013, there were approximately 1.1 million deaths occurring under the care of one of over 5000 hospices.1 Palliative care services have expanded similarly across hospital and community care settings, including acute care units, emergency and critical care departments, outpatient settings, and within innovative community programs for patients with chronic conditions, such as neurological, cardiac, and pulmonary disease.

There are many myths associated with palliative care including that it can only be provided in a hospital and that pain medications used in palliative care lead to addiction. Perhaps the biggest myth is that palliative care represents a resignation or a form of “giving up” by the healthcare provider and signals the beginning of end-of-life care to the patient. The reality is that high-quality palliative care is focused on pain management, control of symptoms, and helping patients reach their specific treatment goals.

The goal of palliative care is improved quality of life for patients and their loved ones. In the urologic oncology field, urologists can play an important role in successful comprehensive care by incorporating palliative care in their treatment regimens.

“Patients should be aware of palliative care options right from the beginning of their diagnosis and treatment,” said Michael Rabow, MD, the Hellen Diller Family Chair of Palliative Care at the University of California San Francisco, Hellen Diller Family Comprehensive Cancer Center. “Palliative care is not just end-of-life care, it is not just limited to patients who are dying.”

The key begins with the urologist, said Rabow, who is professor of clinical medicine and urology. By making palliative care a part of routine urologic care, and especially in cancer care, it can prevent or alleviate, as early as possible, the symptoms and side effects of treatment associated with the disease. The objective of palliative care is not to cure but it should be provided alongside curative treatment. Palliative care is sometimes referred to as comfort care, supportive care, and symptom management.

“As urologists, we need to change our habits so that we can honestly tell patients that part of providing comprehensive care for prostate or renal cancer involves palliative care,” said Rabow. A frank discussion about palliative care should be initiated when the patient’s course of treatment is discussed.

The American Society of Clinical Oncology has come out clearly stating that any patient with metastatic cancer or very high symptom burden should be receiving concurrent palliative care and oncologic care as standard therapy.

“We know that in medicine, once we have good evidence of what we should do, it takes 17 years for it to become standard practice,” said Jonathan Bergman, MD, an assistant professor of urology and family medicine at the Veterans Health Affairs of Greater Los Angeles and the David Geffen School of Medicine at UCLA. “That’s not acceptable. We need to find ways to implement interventions much faster and much more broadly, once we are sure that it’s the right thing do.”

Rabow suggests that one way to incorporate palliative care into the comprehensive care regimen might be to think about palliative care like nutrition or other supportive interventions. The urologist can position the benefits of palliative care and referral to a palliative care specialist in a similar way that nutrition is positioned: As the patient undergoes urologic treatments, the urologist can make concurrent recommendations about nutrition directly, or refer to a nutritionist.

When certain patients require the expertise of a specialist, referrals to palliative care specialists may be warranted. Referring to a palliative care specialist may be particularly difficult for urologists in rural areas. The first step is for the urologist to identify the palliative care resources in the community and start building relationships with palliative care specialists in the area, said Bergman. If possible, schedule patients who are sicker or who are less mobile to see the palliative care specialist during urologic visits, which is helpful and more convenient for patients.

Palliative Care Training for Every Clinician

“Every clinician needs to have some basic palliative care skills,” said Rabow. “We need to start training medical students, residents, fellows, and practicing physicians. They need to know how to start antidepressants, they need to know how to assess basic pain and start opioids for severe pain, and how to manage constipation. We need to start expecting more of the basics of comprehensive cancer care from urologists. Every patient with a urologic cancer should be getting some basic pain management,” and that care can be delivered by the urologist.

By building palliative care into routine urologic care, the idea that palliative care is the default once there are no more treatment options available is avoided. “That’s the message to get out to urologists who may not have learned about modern palliative care during their clinical training.” It also avoids associating palliative care only with hospice care, which is end-of-life care. “Your patients, who are fully expected to survive their cancer, might do better with concurrent palliative care,” said Rabow. “Every patient should be getting some reasonable communication about prognosis and goals of care.”

Urologists should make sure to assess each patient and to understand what each patient’s treatment goals are, said Bergman. “Once the patient’s individual goals are established, urologists can see how best to help them achieve them.”

The Quality and Practice Standards Committee of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association Research Advisory Council have developed a portfolio of valid, clinically relevant, performance indicators, called Measuring What Matters (MWM), for internal measurement by hospice and palliative care programs.

 The portfolio serves as a common core set from which programs can select to help create standards for quality measurement of palliative care in the United States and allow for national benchmarking.

The goal of the program is to create an initial set of process and outcome indicators that apply regardless of diagnosis, organizational structure, or setting, although the MWM team recognized that such indicators may not always be appropriate or not yet exist or may not apply across populations and settings. Promoting high-quality hospice and palliative care indicators for accountability with the Centers for Medicare & Medicaid Services and other groups is also an important goal.

In addition, the National Quality Forum (NQF) Board of Directors approved 14 quality measures on palliative and end-of-life care. The measures address a wide range of care concerns, including pain management, psychosocial needs, care transitions, and experiences of care. NQF sought measures focused on care concerns such as managing pain, weight loss, and depression. It also sought measures that would directly assess—and improve over time&mdash;the experience of patients undergoing palliative and end-of- life care, as well as the experience of their families. In all, 22 measures were evaluated against NQF’s endorsement criteria by a panel of providers, measurement experts, and consumer representatives; 14 measures were endorsed.

“Palliative care teams have been shown to help improve patient care quality throughout the course of treatment,” said R. Sean Morrison, MD, director of the National Palliative Care Research Center in a statement. “This measure set will help support such efforts, such as enhanced treatment of pain and other symptoms, improved communication between providers and patients, fewer admissions to emergency departments, and increased patient satisfaction,” said Morrison, co-chair of the Palliative Care and End-of-Life Care Endorsement Maintenance Steering Committee.

Palliative care in urology seems to be in its infancy. “We need to figure out how to help the practicing urologist know the basics of palliative care,” said Rabow. One tool that he has used is the Edmonton System Assessment Score. “It’s a quick, effective, and validated tool to assess and understand the symptoms a patient is experiencing,” said Rabow. “We can use that to then focus on trying to address the patient’s symptoms.”

Bergman said the first step to addressing the greater use of palliative care begins with educating urologists about the benefits “and then to educate health systems about the fact that not only will their patients do better—their patients will live longer and likely at a lower cost.”

A core element is bringing the patient into the fold by educating him about palliative care. “We want patients to know that we’re actually being aggressive about treating all aspects of their disease, and that includes palliative care management. What we want as urologists is to help them the most we can.”

			National Hospice and Palliative Care Organization. NHPCO facts and figures: hospice care in America. 2014. http://www.nhpco.org/sites/default/files/public/Statistics_Research/2014_Facts_Figures.pdf

			Center to Advance Palliative Care. Analysis of U.S. hospital palliative care programs, 2012 snapshot. 2012. http://reportcard.capc.org/pdf/capc-growth-analysis-snapshot-2011.pdf.

			Morrison RS, Meier DE, Augustin R, et al; Center to Advance Palliative Care. A state-by-state report card on access to palliative care in our nation’s hospitals. 2010. http://reportcard.capc.org/pdf/state-by-state-report-card.pdf.

			Dy SM, Kiley KB, Ast K, et al. Measuring what matters: top-ranked quality indicators for hospice and palliative care from the American Academy of Hospice and Palliative Medicine and Hospice and Palliative Nurses Association. 

Articles

In the urologic oncology field, urologists can play an important role in successful comprehensive care by incorporating palliative care in their treatment regimens.

Start Discussions About Palliative Care Upon Initial Metastatic Diagnosis

New diagnoses of prostate cancer cases declined nearly 30% after the United States Preventive Services Task Force (USPSTF) recommended against routine prostate-specific antigen (PSA) screening for men.

“We demonstrated that following the recommendation, there was an immediate drop in the number of new prostate cancer diagnoses each month,” said Daniel A. Barocas, MD, MPH, an assistant professor of urologic surgery at Vanderbilt University Medical Center. “One year after those draft recommendations, new diagnoses were down by 28%.”

The USPSTF recommendation had a specific aim, which was to reduce the burden of harm associated with prostate cancer detection and treatment. In October 2011, the task force issued a draft guideline discouraging the use of PSA-based screenings for prostate cancer after concluding the harms outweighed potential benefits. Harmful side effects of treatment may include incontinence, erectile dysfunction and radiation cystitis.

To determine the effects of this recommendation, the investigators identified new cancers diagnosed between January 2010 and December 2012 in the National Cancer Database, a far-reaching registry that covers 65% to 70% of all cancer diagnoses. They studied the trend of prostate cancers diagnosed each month before and after the draft guideline, and compared prostate diagnoses with new colon cancer cases. Twelve months after the draft USPSTF guidelines were published, diagnoses of new low-risk cancers had fallen by 37.9% while colon cancer cases remained stable. New prostate cancer diagnoses also declined by 23% to 29.3% among men over age 70 and 26% among men considered infirm.

Barocas pointed out that to a certain extent the USPSTF recommendation does limit the harm done, but “there’s also collateral damage if you take away screening on a broad scale like that. And the collateral damage is in missing opportunities to diagnose intermediate and high-grade disease patients who are candidates for treatment. If you miss those opportunities, you miss the chance to cure the patient and increase the treatment burden if the disease is caught later in its course.”

“The results raise concern that if this trend continues more men may be diagnosed at a point when their disease is advanced. Younger, healthier men with intermediate or high-risk disease would normally be candidates for aggressive local therapy and they may not be receiving a timely diagnosis under this policy.”

The effect of the guideline might minimize the harm, but it also minimizes the benefit, he said. The long-term effect of the recommendation is yet to be seen, “but I hope the USPSTF will pay attention to these types of studies and revise their policies.” At the least, “there may be a more balanced approach to screening that engages the patient in decision making, which presents data in an even-handed way, and allows for early detection in appropriate situations.”

Findings were posted online in the June 15 issue of 

New diagnoses of prostate cancer cases declined nearly 30% after the United States Preventive Services Task Force recommended against routine prostate-specific antigen screening for men.


New Diagnoses of Prostate Cancer Decline Nearly 30% Following USPSTF PSA Decision

Urologists who are in solo practice or not affiliated with a medical school may overuse primary gonadotropin-releasing hormone (GnRH) for men with localized prostate cancer, according to Shellie D. Ellis, PhD, MA, assistant professor of health policy and management at the University of Kansas School of Medicine. These urologists treat more vulnerable populations, which may contribute to health disparities in prostate cancer treatment quality.

Although primary GnRH agonists are recommended for men with metastatic disease and adjuvant to radiation for some men with localized disease, the use of these agents alone in localized disease is recommended only for a small group of patients, making most use in the absence of radiation overuse. Ellis and colleagues described physician-level patterns of overuse and the effect of time in practice and solo practice type on persistent GnRH agonist overuse.

In 2003, the Medicare Modernization Act (MMA) targeted wide variation in physician reimbursement of drugs covered under Medicare Part B (including GnRH agonists). The standardization, implemented incrementally in 2004 and 2005, decreased reimbursement for GnRH agonists by 65%.

With the cut in reimbursement, oncologists responded by increasing the use of recommended chemotherapies. Urologists, on the other hand, maintained GnRH agonist use in patients for whom it was recommended, but decreased overuse in patients for whom it was not recommended. By 2005, GnRH agonist overuse declined by 34%; however, 25.7% of men for whom it was not recommended still received this treatment in 2005.

In the current study, the final sample included 12,943 men diagnosed with T1 and T2 well- or moderately-differentiated prostate cancer from 2000 through 2007, identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, and treated by 2138 urologists, who were identified through the American Medical Association Masterfile.

The researchers found that among men treated between 2000 and 2008, 18.5% received GnRH agonists without other therapy. GnRH agonist overuse decreased from 21.0% before MMA implementation to 17.6% during the implementation phase, and to 13.6% following full policy deployment.

Consistent with other studies, the researchers found that GnRH agonist overuse declined precipitously throughout the 2000s, coincident with reimbursement policy changes. Rates of overuse found in this study were similar to other published estimates and reflected a blending of two previously published sampling strategies and outcome definitions. Further, overuse continued on a downward trajectory in the 2 years following MMA implementation.

Three distinct patterns of GnRH agonist overuse were observed. Urologists’ time in practice was not associated with GnRH agonist overuse (odds ratio [OR] 0.89; 95% confidence interval: 0.75-1.05). However, solo practice type (OR 1.65; 95% CI: 1.34-2.02), medical school affiliation (OR 0.65; 95% CI: 0.55-0.77) and patient race were. Compared with non-Hispanic whites, non-Hispanic blacks (OR 1.76; 95% CI: 1.37-2.27), Hispanics (OR 1.41; 95% CI: 1.12-1.79), and men of “other” race (OR 1.44; 95% CI: 1.04-1.99) had greater odds of receiving unnecessary GnRH agonists.

GnRH agonist overuse remained, with 14% of men with T1 or T2 well- or moderately-differentiated tumors prescribed primary GnRH agonists in the post-MMA period.

Urologists who overuse GnRH agonists also were more likely to lack affiliation with a medical school, which may make them hard to reach for intervention. The authors wrote that medical school-affiliated physicians may have resources (eg, trainees, tumor boards) that encourage guideline-concordant practice; however, they may also lack motivation for financial gain. This professional isolation could make it difficult to engage these urologists in traditional quality improvement efforts, according to the researchers.

The authors concluded that the findings might provide guidance to develop interventions to address overuse in prostate cancer.

Urologists who are in solo practice or not affiliated with a medical school may overuse primary gonadotropin-releasing hormone for men with localized prostate cancer.

Study Says Urologists in Solo Practice May Overuse Gonadotropin Agonists

Men with intermediate- or high-risk prostate cancer experienced higher survival rates when given increased radiation doses than men with low-risk disease, according to researchers from Penn Medicine. In addition, men with low-risk disease but with already-high survival rates were unaffected by higher radiation doses.

Anusha Kalbasi, MD, and colleagues compared the survival rates of 42,481 men who were diagnosed between 2004 and 2006 and followed through 2012 and linked those rates with increased radiation doses in the National Cancer Database. The researchers investigated whether “radiation dose reduction for patients with low-risk prostate cancer could achieve similar cure rates while avoiding the increased risk of side effects associated with higher radiation doses,” said Kalbasi, a resident in the department of radiation oncology at the Perelman School of Medicine at the University of Pennsylvania.

In 2014, low-risk prostate cancer was the most common type of prostate cancer diagnosed in the United States, affecting about 150,000 patients, many of whom undergo aggressive treatment, either complete removal of the prostate or radiation.

Some men received the standard dose of radiation while others received higher doses of radiation. For men with medium- and high-risk forms of prostate cancer, the researchers found that for every incremental increase in radiation dose, there was a 7.8% and 6.3% reduction, respectively, in the rate of death from any cause. For men with low-risk cancer, no differences in survival were found whether they received the standard dosage of radiation or the higher dosage.

For all groups, 7-year adjusted survival rates were determined. In the low-risk group, survival rates were 86% for men who received either the standard dose or higher dose radiation. For the medium-risk group, survival rates were 82% among men who received the higher-dose radiation, and 78% among men who received the standard dose. For the high-risk group, survival rates were 74% in the higher-dose group and 69% in the standard-dose group.

Radiation therapy is associated with side effects and those side effects have been shown to increase with radiation dose, said Kalbasi. For patients undergoing prostate radiation, side effects include, fatigue, urinary frequency and urgency, changes in bowel habits, and erectile dysfunction.

Prostate cancer is the most common cancer diagnosed among American men, and causes more deaths annually among men than any other tumor except lung cancer. However, a large majority of men found to have prostate cancer ultimately die of other causes, prompting researchers to conduct studies to identify who benefits most from treatment and what those treatments should be.

“Our findings show that the dose of radiation should be personalized to the specific characteristics of the prostate tumor,” Justin Bekelman, MD, associate professor of radiation oncology at the University of Pennsylvania School of Medicine, said in a statement.

“For some patients, personalized treatment will lower the chances of toxicity while maintaining similar survival rates; for other patients, personalized treatment will mean escalating radiation dose to achieve the highest survival while protecting normal tissues, like the bladder and rectum.”

Men with intermediate- or high-risk prostate cancer experienced higher survival rates when given increased radiation doses than men with low-risk disease.

Men With Intermediate or High-Risk Prostate Cancer See Survival Benefit From Increased Radiation Therapy

Patients who were taking statins while also undergoing androgen deprivation therapy (ADT) may experience a reduction in all-cause and prostate cancer-specific deaths, according to new research from the Dana-Farber Cancer Institute. A retrospective study involving statin use was conducted in 926 patients who had received ADT for biochemical or metastatic recurrence or de novo metastatic prostate cancer between January 1996 and November 2013. Findings were published in 

Analyzing prostate cancer cell lines, the researchers also demonstrated that statins and dehydroepiandrosterone sulfate (DHEAS), a precursor of testosterone, compete for the SLCO2B1 cellular transporter, which facilitates entry into prostate cells, thus providing a potential mechanism of action.

The analysis revealed that 31% of patients were taking a statin—atorvastatin, fluvastatin, pravastatin, or simvastatin&mdash;at ADT initiation. After a median follow-up of 5.8 years, 644 patients (70%) had experienced disease progression while receiving ADT. Median time to progression (TTP) during ADT was 20.3 months (95% CI, 18-24 months). Men taking statins had a longer median TTP during ADT compared with nonusers (27.5 [95% CI, 21.1-37.7] vs 17.4 [95% CI, 14.9-21.1] months; 

In addition, researchers saw a 17% reduction in the hazard of progression during ADT after adjusting for predefined prognostic factors (adjusted hazard ratio, 0.83; 95% CI, 0.69-0.99; 

 = .04) such as Gleason score at biopsy, type of primary therapy be it radical prostatectomy or radiotherapy, use of ADT with the primary therapy, or presence of metastases and PSA level at ADT initiation.

Statins are administered widely in the United States for their clinically meaningful lipid-lowering properties. Most epidemiological studies have shown significant associations between statin use and decreased incidence of advanced prostate cancer, risk of recurrence after local treatment, mortality, and PSA levels relative to nonusers.

SLCO2B1 is an organic anionic transporter that allows a number of anticancer compounds and hormones to enter cells. Chief among its substrates is the adrenal androgen dehydroepiandrosterone sulfate (DHEAS), which is a precursor to more potent androgens. Among the potent androgens is dihydroxytestosterone (DHT), which binds to the androgen receptor in normal and cancer cells. In prostate cancer, expression of SLCO2B1 increases on progression from hormone-sensitive to castration-resistant disease.

Continued reliance of the tumor on androgen receptor signaling and residual androgens contributes to progression to castration-resistant prostate cancer (CRPC). In the study, Lauren C. Harshman, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and colleagues found that DHEAS and various statins compete for binding to the transporter SLCO2B1. They theorize that statins can competitively inhibit DHEAS uptake.

Given the biologic heterogeneity observed in prostate cancer, what becomes clear is that the ability of a therapy to thwart the development of lethal prostate cancer is more important than decreasing the overall incidence, wrote the authors.

The authors concluded that the mechanism through which statins exert their activity in prostate cancer is likely “multifactorial, including antiproliferative and proapoptotic effects.” The authors suggest that the most plausible mechanism may be attributed to a reduction in the tumor’s androgen stores through a combination of decreased availability of the cholesterol precursor required for de novo synthesis and decreased transport of existing precursor androgens such as DHEAS via competitive binding of SLCO2B1.

“These findings are preliminary, so I would not recommend that everybody start on statins to slow prostate cancer,” senior author Philip Kantoff, MD, chief of solid tumor oncology at the Dana-Farber Cancer Institute in Boston, said in a statement. Also, Kantoff cautioned that these findings apply only to men who have advanced prostate cancer that has relapsed after androgen deprivation therapy. “This does not speak to early-stage prostate cancer or whether statins are beneficial in preventing prostate cancer,” he said.

Patients who were taking statins while also undergoing androgen deprivation therapy may experience a reduction in all-cause and prostate cancer-specific deaths.

Concurrent Statin Use in ADT Patients Reduced All Cause, Prostate Cancer-Specific Deaths

Final survival data for pre-chemotherapy use of abiraterone from the COUGAR-AA-302 study demonstrated a median of 35 months for men with castration resistant prostate cancer. The findings compared favorably with the median survival of 30 months in patients treated with prednisone and placebo, initially, said Charles J. Ryan, MD, professor of medicine and urology at the Hellen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, during an interview with 

From April 2009 to June 2010, 1088 patients were randomized to receive abiraterone with prednisone or prednisone with placebo. Initial outcomes data for progression-free survival (PFS) were released in 2012, but mature survival data were not achieved until mid-2015, said Ryan. During the time of this study, abiraterone was approved and became available in most countries participating in the clinical trial.

“As a result, 44% of the patients who were initially enrolled in the placebo arm went on to receive abiraterone,” said Ryan. There was also a significant amount of subsequent therapy with docetaxel, cabazitaxel, and enzalutamide in both arms of the study, explained Ryan. This resulted in survival curves that required a relatively long period of time to fully mature, which explains why the 2012 data did not demonstrate statistically significant endpoints while the 2015 follow-up analyses confirmed significance.

“But when one sees the evolution of the curves, one sees that when we did that initial presentation and publication, the curves were really just beginning to separate,” said Ryan. “And by the time we get to the median follow-up that we have now, we see a significant and persistent separation of the survival curves.”

At the final 49.2-month analysis of the COU-AA-302 study, the median overall survival (OS) was 34.7 months with abiraterone versus 30.3 months with placebo (HR = 0.81; 

 = .0033). The median radiographic professional-free survival (rPFS) with abiraterone acetate was 16.5 months compared with 8.3 months for prednisone (HR = 0.53;

Clinical progression, either clinical progression only or in combination with radiographic progression, was seen in 39% of the patients, which was clinically significant. Clinical-only progression was defined as pain requiring opioids, the need for chemotherapy or palliative radiation therapy, a decline in Eastern Cooperative Oncology Group performance status, or surgical intervention, and 26% met at least one of these criteria.

After protocol, the rate of subsequent therapy with either cabazitaxel, docetaxel, and enzalutamide was similar in both groups. Some 44% of patients randomized to placebo crossed over to abiraterone acetate while 13% of those randomized to abiraterone acetate were re-treated with abiraterone.

At the final analysis, the risk of death was reduced by 19% in the abiraterone acetate arm, with the median OS prolonged from 30.3 months in the placebo arm to 34.7 months in the abiraterone acetate arm (

 =.0033). Forty-four percent of patients randomized to placebo crossed over to abiraterone acetate. The iterative parameter estimate (IPE) adjustment improved the reduction in the risk of death with abiraterone acetate to 26% (

 <.0001). When adjusting for baseline prognostic factors, abiraterone acetate led to a 21% reduction in the risk of death (

Baseline characteristics were similar between the two randomized groups, including median time from initial diagnosis to first dose (5.5 years in patients randomized to abiraterone acetate vs 5.1 years in patients randomized to placebo), median level of prostate-specific antigen (42.0 ng/mL vs 37.7 ng/mL), the percentage who had Gleason grade ≥8 disease at initial diagnosis (54% vs 50%), and the extent of disease including the percentage with bone metastases (83% vs 80%). About half in each group had ≥10 bone metastases.

A secondary endpoint in COU-AA-302 was time to first opiate use. COU-AA-302 enrolled patients who had very little to no pain that was associated with their disease, and, in fact, patients were required to not be taking opiates at the time of enrollment. Patients receiving abiraterone went 1 year longer than patients in the placebo arm without requiring opiate analgesics. “The development of pain is a major landmark in metastatic prostate cancer,” said Ryan.

“That’s quite a significant time when you think about it, one year less of opiate requirement, and so that’s a very critical, I think, clinical useful and very meaningful endpoint that clinicians and patients can relate to. Interestingly, it took a long time for the majority of patients on the study to require opiates, and so this was one of the later endpoints that matured.”

While some clinicians may discontinue abiraterone therapy based on a rise in PSA level, Ryan advises against this approach because continuing therapy may still help slow down the progression of disease. However, he says, for patients who are developing progressive disease with new lesions on bone scans or new visceral metastases, discontinuation of abiraterone is clinically prudent.

When to discontinue abiraterone during the patient’s regimen is difficult to answer. According to the COUGAR study, patients did not discontinue abiraterone because of a rising prostate-specific antigen. “In fact, there was a fairly lengthy time interval between when PSAs began to rise and when radiographic progression occurred. In many cases, it’s 6 or 7 months, and, in some cases, I’ve had patients who continue to take abiraterone for well over a year or even longer without requiring discontinuation.” Discontinuing abiraterone because of a simple rise in PSA may actually be doing patients a disservice. “Continuing the therapy may continue to slow down the progression of the disease, and some of the data we have from the 302 study bear that out.”

“If a patient is developing progressive disease with progressive symptoms and objective progression, new lesions on bone scan or new visceral metastases, it’s clinically prudent to discontinue the abiraterone.”

Ryan cautioned that “there are patients who will progress and may exhibit symptomatic progression. These patients can be treated with radiation therapy. I’d urge clinicians to evaluate progression as its own event and look at it and ask the question, ‘Is it global progression?’ ‘Does it involve multiple sites and general decline?’ Or is it an isolated progression? If it’s an isolated progression, consider either a focal radiation therapy or something along those lines.”

Demonstrating Overall Survival in Metastatic Prostate Cancer

There are several challenges in demonstrating an improvement in overall survival in metastatic prostate cancer, said Ryan.

There are multiple agents available for patients, and “so if we want to test something in metastatic castration resistant prostate cancer (mCRPC), we’re going to require or allow that patients would receive subsequent therapy.” He said there are numerous chemotherapies available. The challenge is that “once you begin lining up a series of therapies, all of which have survival benefits, it becomes statistically quite difficult to demonstrate survival benefits.” That makes subsequent therapy a major challenge.

He said that the other major challenge in the design of phase III trials of mCRPC is the fact that this is a chronic disease and patients live a long time. “That’s a clinically good thing but it’s a challenge in terms of designing a phase III trial. So, when one considers initiating a trial in the current era with all these available therapies, and we now have data to show that the median survival for patients with mCRPC is about three years, you’re talking about a five- or six-year endeavor in order to design, run, and read out phase III trials.”

When non-metastatic castration resistant prostate cancer is considered, it is even more challenging because the patients are in an even earlier clinical state. “So the trials that are taking place in that area of non-metastatic CRPC or the early asymptomatic CRPC state, are generally getting larger, accruing 1400 or 1700 patients, and are taking longer. That becomes a pretty significant resource impediment.”

With the advent of a number of therapies for metastatic castration resistant prostate cancer, researchers are now looking at patients who are castration resistant but exhibit no disease spread.

One group of patients exist because of early use of androgen deprivation therapy (ADT) for patients with a serologic relapse, sometimes referred to as the “PSA-only patient,” said Ryan. The other group is less common and are characterized by metastases in the lymph nodes, for example, who start on ADT, and then ultimately progress by having a prostate-specific antigen (PSA) rise. However, imaging scans reveal no evidence of metastatic disease.

“These patients don’t really fit into the standard of care guidelines that govern metastatic disease,” said Ryan.

During this year’s American Urologic Association meeting, Ryan presented results from a Phase II study involving 125 patients who were treated with abiraterone and low-dose prednisone. The study was designed to measure PSA changes.

Ryan reported that “87% of patients who received abiraterone had a 50% decline in their PSA. That’s a higher percentage of patients having a PSA decline than we saw with metastatic disease.” This group has not met the median progression free survival.

“This study is ongoing and it will provide some very important insight into the efficacy of abiraterone in that setting.”

	Impact of crossover and baseline prognostic factors on overall survival (OS) with abiraterone acetate (AA) in the COU-AA-302 final analysis. Presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL. Abstract 142.

Charles J. Ryan, MD, discusses the final survival data for pre-chemotherapy use of abiraterone from the COUGAR-AA-302 study, which demonstrated a median of 35 months for men with castration resistant prostate cancer.

August 2015 | Oncology Live Urologists in Cancer Care®

Start Discussions About Palliative Care Upon Initial Metastatic Diagnosis

New Diagnoses of Prostate Cancer Decline Nearly 30% Following USPSTF PSA Decision

Study Says Urologists in Solo Practice May Overuse Gonadotropin Agonists

Men With Intermediate or High-Risk Prostate Cancer See Survival Benefit From Increased Radiation Therapy

Concurrent Statin Use in ADT Patients Reduced All Cause, Prostate Cancer-Specific Deaths

Improved Survival Data Seen With Abiraterone as COUGAR Trial Concludes