PARP, CTLA-4, PD-L1, VEGF, HER2/Neu, PI3K/AKT/mTOR, PIP, Hsp90A, BRAF, cMET, SPARC, PTEN, CAR-T, AR-V7, NK92: the lexicon in the world of genomics, proteomics, and targeted therapies continues to expand and permeate into the urology literature. However, no longer is it unique to those doing basic science research. It will soon become part of our clinical vocabulary as well. The world of precision medicine is upon us and we as providers, especially those involved in the management of oncology patients, will need to be conversant and have an understanding of these various pathways and drivers in order to more effectively manage our patients.

For those who attended the annual meeting of the American Urological Association (AUA) and possibly the American Society of Clinical Oncology (ASCO) two weeks later, the number of abstracts and presentations that focused on the use of “—omic” pathways, whether it be diagnostic, therapeutic, or prognostic, was astounding. For prostate cancer, the opportunities and challenges are seemingly endless: Whom to biopsy? Whom to treat or not treat? Whom to rebiopsy? Who will best respond to secondary hormonal manipulation versus cytotoxic therapy versus immune therapy, and when to change therapy? What are the resistance mechanisms? Are they primary or acquired?

There are many open questions in the area of urothelial cancers. Which patients with nonmuscle invasive bladder cancer (NMIBC) will progress to muscle invasive (MIBC) disease? Who are the patients with NMIBC that may not need cystoscopy every three months and would it be blasphemy to suggest it in a urology publication? Are there signatures in MIBC patients that will respond to neoadjuvant chemotherapy versus those who should forego chemotherapy up front? What is the significance of the early promising results of the anti-PD1/PD-L1 therapies in MIBC? Will they play a role in combination with bacillus Calmette-Guérin (BCG) in NMIBC?

As we have discussed many times in this publication, the role of the urologist in the management of our cancer patients is rapidly evolving. We can no longer just be proceduralists or diagnosticians. We will need to think more like clinical scientists. However, the basic approach will fundamentally be the same. From a surgical standpoint, for the most part, the best outcomes are a result of knowing the indications for a particular procedure and applying it to the correct patient clinical scenario. Hopefully, one would offer urethrectomy at the time of radical cystectomy for patients with MIBC that have prostatic urethra or bladder neck involvement. The same intellectual processing needs to take place as we move into the molecular space with the use of —omic data to determine appropriate therapeutics.

The challenge of sequencing and combining drugs is far from clear, and this will only become compounded as companies and the FDA want to fast-track more and more targeted therapies with no biomolecular markers to guide us and only the clinical patient presentation and organ of origin. Are we making progress? Absolutely. But there is still much to be learned and discovered: circulating tumor cells (CTCs), cell free DNA, micro RNA, etc. These represent another set of abbreviations and verbiage that 10 years ago we as surgeons would have never dreamed that we would need to know in order to optimize patient care. These assays are very much still in their infancy and, as we are all aware, none of them are entirely reproducible or reliable, nor commercially available (let alone reimbursable). However, it is estimated that the number of cancer survivors in the United States requiring care by the year 2020 will be 18.1 million patients at an estimated annual cost of $173 billion. The biggest drivers of this increase, relative to 2010, will be prostate and breast cancer, up 42% and 32%, respectively.

 The cost of each therapy approaches $100,000. It is an unsustainable spiraling cost that the system cannot tolerate.

As payment reform continues and we, as a specialty, want to be the flag bearer for urologic malignancies, it is imperative that we make every attempt to evolve from the classically trained urologic surgeon to the urologic scientist. Yes, next generation sequencing (NGS) often provides us with more questions than answers. Many of the epitopes identified do not have approved targeted drugs. But in order for us to remain relevant in the world of urologic oncology, we must continue to keep pace with all these scientific breakthroughs, not only to offer optimal patient care but also to be fiscally prudent in our therapeutic decisions.

	Mariotto AB, Yabroff KR, Shao Y, et al. 

Articles

The world of precision medicine is upon us and we as providers, especially those involved in the management of oncology patients, will need to be conversant and have an understanding of these various pathways and drivers in order to more effectively manage our patients

Grasp of Clinical Science Now a Necessity in Urologic Oncology

In the oncology realm, specialty pharmacy has become a mainstay, but its role in urology practice is starting to trend upwards. Defined as a market space of products that have a significant per dose or per monthly expense associated with them, specialty pharmacy may offer urologists a way to manage their prostate cancer patients before referring them to a medical oncologist, according to our article, “Specialty Pharmacy Makes Inroad in Pharmacy Practice.”

Eric Sredzinski, PharmD, RPh, would agree. “Specialty pharmacy and urology are at a crossroads,” says the executive vice president of Clinical Affairs and Quality Assurance for Avella Specialty Pharmacy.

Incorporating specialty pharmacy is not an easy endeavor, however. As with any investment, time and capital are required, and a urology practice has to start with an understanding of the current volume of prescriptions being written and filled. Ultimately, specialty pharmacy can be useful to maintain the continuity of care for the patient—something that all urologists want.

We also report on a recent “OncLive Insights Expert Perspectives” panel, moderated by Daniel P. Petrylak, MD, director of the Genitourinary Oncology Research Program at the Yale Comprehensive Cancer Center. He was joined by Dean F. Bajorin, MD, an attending physician at Memorial Sloan Kettering Cancer Center and Evan Y. Yu, MD, professor in the Department of Medicine at the University of Washington and the Seattle Cancer Care Alliance.

The panel discussed the growing and exciting emergence of immunotherapy in bladder cancer, highlighting the checkpoint blockade inhibitor MPDL3280A. The FDA has designated the agent as a breakthrough therapy in bladder cancer.

The panelists discussed ongoing clinical trials, including a phase II, multicenter, single-arm study of MPDL3280A in patients with locally advanced or metastatic urothelial bladder cancer (NCT02108652).

In that trial, researchers are evaluating MPDL3280A (1200 mg) every 21 days for up to 16 cycles in 300 cisplatin-refractory patients and 100 treatment-naïve and platinum-ineligible patients.

“It’s going to be interesting to see whether platinum in-eligible patients who are chemotherapy naïve will respond or not,” said Petrylak during the discussion.

The Large Urology Group Practice Association, or LUGPA, has a new president-elect—Neal Shore, MD, of Atlantic Urology Clinics, an affiliate of 21st Century Oncology. Shore joined us in our studios at the OncLive News Network and discussed his new responsibilities at the organization and talked briefly about the role of radium-223 in urology practice.

Rounding out this issue are highlights from the 110th Annual Scientific Meeting of the American Urological Association (AUA) and the 2015 ASCO (American Society of Clinical Oncology) Annual Meeting.

At the AUA, some of the broad subjects covered include improved and smarter screening techniques, active surveillance, and biomarkers. In particular, the use of biomarkers may aid urologists in smarter screening techniques by better identifying higher-grade cancers and minimizing overall biopsy rates.

Overtreatment was a strong theme emphasized during the AUA meeting, especially findings that revealed a 50% drop in PSA testing after the USPSTF (United States Preventive Services Task Force) gave the screening test a grade of “D,” back in 2012 and did not recommend its use by primary care physicians. The recommendation is slowly sending prostate cancer diagnosis backward 20 years, according to some experts.

We also highlight the growing use in the United States of active surveillance. The strategy has become a viable option for many men with low-risk prostate cancer who choose not to undergo active treatment—including surgery or radiotherapy.

At ASCO, the role of docetaxel in prostate cancer was highlighted in two studies. We noted the first ever study of adjuvant chemotherapy use in high-risk, localized prostate cancer. In the study by Sandler et al, the 4-year overall survival rates were 89% for men who received androgen deprivation therapy and radiation therapy versus 93% for men treated with androgen deprivation therapy, radiation therapy, and docetaxel. In another study from ASCO, the addition of docetaxel to standard hormonal therapy significantly improved survival among men with newly diagnosed, hormone-naïve advanced prostate cancer.

In the oncology realm, specialty pharmacy has become a mainstay, but its role in urology practice is starting to trend upwards. 

Urology Practice and Specialty Pharmacy Meet at a Crossroads

The use of specialty pharmacy in oncology practice has grown, becoming a mainstay for many practices. Historically, that has not been the case for urology practices, but that trend is changing as more urologists see the potential of managing their prostate cancer patients with oral oncolytics, rather than referring them immediately to medical oncologists. There are many processes for a urology practice to consider when partnering with a specialty pharmacy, including time and capital investments. Challenges include prior authorization, storage of medications, adherence, and benefits investigations.

“I think it’s a newer trend in actually a number of clinical specialties and urology would certainly be one of them,” said Richard Demers, RPh, MS, assistant executive hospital director for pharmacy services at the University of Pennsylvania. “The term specialty pharmacy defines a market space of products that have a significant per dose or per month expense associated with them. They also often require prior authorization from payers in order to be covered.”

Eric Sredzinski, PharmD, concurs. “I would say urology and specialty pharmacy are at a crossroads at this point.” With the approvals of medications for advanced prostate cancer, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi) “we are starting to see more urology practices working with specialty pharmacy,” said Sredzinski, an executive vice president of Clinical Affairs and Quality Assurance for Avella Specialty Pharmacy.

The trend is growing for a number of reasons, including the need for increased patient support from a prior authorization perspective or a narrow distribution network for particular agents. Although abiraterone and enzalutamide have limited distributed, “some agents have closed distribution channels so there are very few people who can purchase those products,” said Demers.

Additionally, “manufacturers have implemented processes to direct these prescriptions through a centralized hub,” said Sredzinski. “In our case, we have a specific team dedicated to urology. We have streamlined the process so that we can work with the office conducting the benefits investigation to determine where the coverage lies for that prescription.”

When a practice is considering seeking a relationship with a specialty pharmacy, the first step is to understand how the practice is currently configured. Sredzinski says the practice needs to ask how it currently manages their patients and who is involved. Who are the main points of contact within the organization? What outcomes do they want to achieve, and what kind of communication do they want from the specialty pharmacy?

Once those questions are answered, his company “seeks to provide an overlay on what the practice is currently providing and create enhanced services.” The practice manager should understand what the specialty pharmacy is doing during different time points—how the specialty pharmacy is providing counseling, how the information is being provided to patients, and if any issues need to be escalated and addressed by the urologist. Any data or feedback should be provided back to the practice manager, who can then use it to improve patient outcomes.

Specialty pharmacy also adds a level of complexity to patient care, usually to the patient’s benefit. Specialty pharmacies are particularly adept at dealing with financial issues, exploration and explanation of member benefits, and providing patient support. Also, many specialty pharmacy medications require special storage facilities and processes. Specialty pharmacies can ensure the integrity of the agent through the distribution process, from the manufacturer, to storage, and to final delivery to the patient.

These requirements might be new to the urology practice staffers and the set of activities to handle specialty pharmacy medications could be beyond the scope of the staff’s experience.

“Because of the added activity that needs to occur around these therapies, as far as control and access and patient teaching, finding a good partner on the specialty side is probably very valuable to a urology practice,” said Demers.

In addition, specialty pharmacy is particularly focused on patient education and improving patient adherence, Sredzinski explains. “Our specialty pharmacy, for example, will call the patient at the initiation of therapy and then mid-cycle in their therapy regimen to make sure that the patient is adhering to their medications and if they have any issues, we’re helping to address them at that point in time.”

Specialty pharmacy also gets involved in financial assistance, added Demers. Acting at the interface between the patient and the payer, specialty pharmacy ensures the patient can get access to the medications. Because of the high cost associated with these medications, there are a number of considerations, said Demers.

Some practices do not have the ability to dispense the product or to adjudicate the product through the insurer, so this is an added expense to the practice that is not accounted for by an additional revenue stream. “This is not reimbursable,” said Demers.

A big component of specialty pharmacy is navigating the landscape of insurance and the benefits for the patients, said Sredâ€¨zinski. “For instance, we would work with the urologist’s office to determine what insurance the patient has and what the coverage criteria looks like. Then, assist with the processing of prior authorization and ensure that the appropriate forms are used.

“There is the overall cost of the medication and whether the payer will in fact support paying for the medication in general. Typically many of the payers have a significant copayment associated with the product and those copayments can be quite substantial for the patient. Many specialty pharmacies, ours included, work with either drug companies or other sources to obtain funds to offset some of the copayment responsibility for patients,” said Sredzinski.

In this current environment in which high copayments and cost shifting becomes the patient’s responsibility, the patients’ financial exposure can be very high, said Sredzinski. Specialty pharmacy can work to explore and exhaust all avenues for copayment assistance, whether that is a copayment card that can be leveraged through commercial or private insurance, or working with a foundation that can provide copayment support. The end goal is to drive that copayment down to near zero. The last avenue would be working with the manufacturer to get free access to the drugs for patients who don’t qualify financially. “The specialty pharmacy is doing a lot of work on the front end to ensure the medication gets to the patient, which alleviates a lot of the work on the urology office.”

And that includes actual patient care. Specialty pharmacy discusses adverse drug event management, disease state management, and adherence programs. Many factors go into helping manage these drugs for these patients. “Many of the offices that we work with, even the oncology practices, don’t have the process and employees to ensure that the patients really get the optimal experience when being prescribed these drugs,” said Sredzinski.

A strong specialty pharmacy can take on much of the financial evaluation and patient assistance duties, while improving practice efficiencies.

“Through the specialty pharmacy, the practice knows when the patients are ordering the drugs, when the patients are getting the drugs, and presumably that patients are taking the drugs. And physicians have a better handle to monitor the patients taking the medication,” said Richard Harris, MD, president and chief executive officer of UroPartners, an integrated practice of more than 55 experienced urological specialists, pathologists, and radiation oncologists.

By incorporating a specialty pharmacy, urologists can maintain that continuity of patient care. It is an advantage of many large groups, said Harris.

Successful integration of a specialty pharmacy into a urologic office depends on the volume of prescriptions. Office staff can spend long periods on the phone navigating the insurance process. “There can be a significant savings to the office and the redeployment of the staff to actually managing patients versus being on the phone” added Sredzinski.

Sredzinski is confident that “once the practice manager sees how seamless it is to work with a specialty pharmacy, the in-office drug dispensing model becomes more of an administrative burden.”

The benefits of working with a specialty pharmacy are numerous. Urology practices may see an opportunity to use specialty pharmacy in achieving the important goal of a successful outcome for the patient.

There are many processes for a urology practice to consider when partnering with a specialty pharmacy, including time and capital investments. 

Specialty Pharmacy Makes Inroads in Urology Practice

Using an allograft made up of dehydrated human amnion/chorion membrane (dHACM) wrapped around the neurovascular bundle (NVB) during nerve-sparing robot-assisted radical prostatectomy (RARP) improved continence and potency postsurgery, according to results of a small study conducted by Vipul R. Patel, MD, professor of urology, University of Central Florida College of Medicine and medical director, Global Robotics Institute at Florida Hospital Celebration Health. Findings were published online in 

“The use of dHACM in the wound care field led urologists to consider using these grafts in patients undergoing PARP,” said Patel.

Although PARP has many advantages, including enhanced magnification, 3D vision, and the dexterity of miniaturized instrumentation, the recovery period is characterized by incontinence and impotence, most likely the result of the inflammatory response caused by traction injury to the NVB.

Researchers analyzed postoperative outcomes in 58 men who were preoperatively potent and continent and who had undergone full nerve-sparing PARP. Overall, 58 patients had dHACM placed over each NVB as a nerve wrap after extirpative RARP. These patients were computer-matched with a similar group of 58 men who did not receive a dHACM allograft.

A single surgeon performed all the RARP procedures using the transperitoneal six-port technique with a Da Vinci surgical system. Bilateral, retrograde, athermal nerve-sparing RARP was performed in each patient, with bladder neck reconstruction, an anterior suspension stitch, and posterior reconstruction.

The wrap was placed around the NVB after extirpative RARP, post anastomosis. The dHACM study cohort (group 1; n = 58) was computer-matched with a similar group of patients who did not receive a dHACM graft (group 2; n = 58) in a multivariate design to create homogeneous groups.

All patients in both groups completed an eight-week follow up period, with an average follow-up of four months. The researchers report that continence returned at eight weeks in 81.0% of patients in group 1 and 74.1% of patients in group 2 (

The mean time to achieve continence was shorter in group 1 (1.21 months) than in group 2 (1.83 months; 

 = .033). During the same period, potency returned in 65.5% of patients in group 1 and 51.7% of patients in group 2. The mean time to potency was significantly shorter in group 1 (1.34 months) than in group 2 (3.39 months; 

 = .007). The analysis also showed higher scores on the Sexual Health Inventory for Men questionnaire in the allograft cohort than in the non-allograft cohort. No adverse effects related to dHACM placement were reported.

The results suggest that the use of dHACM facilitates early return to continence and potency. The mean times to potency and continence were significantly shorter in the allograft group. Other uses of dHACM include the treatment of wounds, burns, corneal injuries, chronic venous ulcers, and chronic wounds.

“The use of tissue allografts such as AmnioFix in urology is an evolving field,” said Patel. An adequately powered prospective randomized trial and cost-benefit analysis of dHACM around the prostatic NVB are now under way to further ascertain the treatment effect of this new approach. The researchers concluded that their short-term results are encouraging for patients undergoing full nerve-sparing RARP and dHACM placement.

Patel VR, Samavedi S, Bates AS, et al. Dehydrated human amniotic membrane allograft nerve wrap around the prostatic neurovascular bundle accelerates early return to continence and potency following robot-assisted radical prostatectomy: propensity score—matched analysis. 

Using an allograft made up of dehydrated human amnion/chorion membrane wrapped around the neurovascular bundle (NVB) during nerve-sparing robot-assisted radical prostatectomy improved continence and potency postsurgery, according to results of a small study.

Amnion/Chorion Wrap Improves Outcomes Following Robot-Assisted Prostatectomy

Interest is high among urologists and medical oncologists with “the explosion of checkpoint blockade inhibition studies” that initially made inroads in melanoma and non-small cell lung cancer (NSCLC), but is also gaining traction in bladder cancer, said Daniel Petrylak, MD, director of the Genitourinary Oncology Research Program and co-director of the Signal Transduction Program at the Yale Cancer Center during an OncLive Insights Expert Perspectives program about the management of muscle-invasive bladder cancer.

He was joined on the panel by Dean F. Bajorin, MD, an attending physician at Memorial Sloan Kettering Cancer Center and professor of medicine at Weill Medical College of Cornell University, and Evan Y. Yu, MD, associate professor in the Department of Medicine, Division of Oncology at the University of Washington, Seattle Cancer Care Alliance.

Considering that there have been no major increases in survival in bladder cancer in more than 30 years, immunotherapeutic approaches are welcome in this setting. The rationale for investigating immunotherapy in bladder cancer gained interest because of the positive results of bacillus Calmette-Guérin (BCG) therapy in superficial disease. The use of BCG has resulted in significantly improved outcomes for patients with non-muscle invasive bladder cancer.

 demonstrated that the anti-programmed death-ligand 1 (PD-L1) antibody, MPDL3280A, is highly active, especially in bladder cancer. MPDL3280A is a high-affinity, engineered human anti-PD-L1 monoclonal immunoglobulin-G1 antibody that inhibits the interaction of PD-L1 and B7.1. The effect can restore antitumor T-cell activity and enhance T-cell priming.

“If you look at the patients who are high expressers of PD-L1, the collective response rate in that group was 52%. In contrast, in patients who were low expressers, their response rate was 11%,” said Bajorin, MD. “It really looks like the activity of the drug follows the biology of the development of the drug.” He added that the patients in the trial were generally frail and had multiple comorbidities.

Another significant characteristic is the agent’s relatively favorable toxicity profile, including a lack of renal toxicity. “Most of what we’re seeing is fatigue and rash, but no major toxicities. It’s not like what we have seen with chemotherapy in this patient population before, and that’s encouraging,” continued Bajorin.

 study demonstrated the durable response seen in patients. “It’s encouraging because the median progression free survival in some of the older studies was 2½ months. Yet, we are seeing swimmer plots that are going out in quite lengthy responses,” said Bajorin.

This extended durable response has resulted in stable disease, too, added Evan Y. Yu, MD. Treating patients on a long-term basis with MPDL3280A is encouraging, said Petrylak. He said that he has seen three complete responses and one patient is now approaching two years of treatment.

“It’s unlike what we’ve seen with some of the other CTLA-4 antibodies where patients could develop hypophysitis or develop gastrointestinal complaints, colitis, and liver function test abnormalities,” said Petrylak. Because the response rate is rapid, patients can be evaluated earlier in the treatment regimen. “I think the whole issue about trying to figure out who is going to respond and who is not going to respond is really a crucial one.”

Tumors that respond to immune therapy tend to have high mutational rates and they tend to be tumors that have been exposed to external carcinogens like tobacco or other chemicals. As the tumor evolves over time, “PD-L1 expression can be affected based on exposures,” said Yu. This characteristic may be one of the reasons why bladder cancer is unique with its response rates, added Petrylak.

MPDL3280A was granted breakthrough status by the FDA last year based on phase I data, and additional studies of the agent in urothelial bladder cancer (UBC) are planned and ongoing. A phase II, multicenter, single-arm study of MPDL3280A in patients with locally advanced or metastatic UBC (NCT02108652) is evaluating MPDL3280A (1200 mg) every 21 days for up to 16 cycles in 300 cisplatin-refractory patients and 100 treatment-naïve and platinum-ineligible patients.

“It’s going to be interesting to see whether platinum ineligible patients who are chemotherapy naïve will respond or not,” said Petrylak. “We may see a very different pattern based upon prior exposure to chemotherapy or other agents.”

The challenge of immunotherapy in genitourinary cancer, and bladder cancer in particular, concerns pseudo-progression. As the name suggests, the inflammatory response looks like disease progression, but it actually is not. It may precede a good and prolonged response to the immunotherapy. But because it looks just like progression on scans, it is important to know about it and avoid discontinuing a potentially very effective treatment based on a misinterpretation of what the scans suggest.

This concern will be addressed by the current set of clinical trials involving checkpoint inhibitors. “Physicians can treat beyond that initial progression and wait until the next time point to see if pseudo-progression is the cause,” said Yu. “It will require that clinicians rethink our response criteria,” added Petrylak.

That is not always a bad problem to have, said Bajorin. “We have an active class of drugs, and needing to decipher what might contribute to activity is a good problem to have, especially as more research is conducted.”

The future of immunotherapy in bladder cancer looks promising. The drug pipeline in this arena is quite robust, said Petrylak. Understanding the mechanism of response and next- generation sequencing will play a major role for future studies.

“We are involved in a large trial that is looking at targeted therapy with monoclonal antibodies that are linked to cytotoxic agents. Integrating these treatments, looking at particular markers, and understanding how to target tumors better is going to be a trend in the future,” said Petrylak.

“These are exciting times for bladder cancer,” concluded Petrylak. “I think that a lot of things are beginning to converge.”

			Powles T, Vogelzang NJ, Fine GD, et al. Inhibition of PD-L1 by MPDL320A and clinical activity in patients with metastatic urothelial bladder cancer (UBC). Presented at the annual meeting of the American Society of Clinical Oncology, May 31, 2014.

			Bellmunt J, Petrylak DP, Powles TB, et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in pts with metastatic urothelial bladder cancer (UBC). Presented at the European Society for Medical Oncology 2014, September 29, 2014. 

Interest is high among urologists and medical oncologists with "the explosion of checkpoint blockade inhibition studies" that initially made inroads in melanoma and non-small cell lung cancer, but is also gaining traction in bladder cancer.

Progress in Immunotherapy Continues, But Pseudo-Progression Is a Concern

Two urine biomarkers, aquaporin 1 (AQP1) and perilipin 2 (PLIN2), could be the key to the development of a simple urine test that leads to the detection of asymptomatic, early-stage kidney cancer, according to a recent study. Typically silent, renal cell carcinoma (RCC) is often detected fortuitously during an abdominal CT or MRI scan, said co-investigator Evan D. Kharasch, MD, PhD, the Russell D. and Mary B. Shelden Professor of Anesthesiology at Washington University School of Medicine in St. Louis, Missouri.

“It is not affordable to use abdominal imaging as a population screening method, so our goal has been to develop a urine test to identify kidney cancer early and noninvasively,” said Kharasch. When kidney cancer is not discovered until after it has spread, more than 80% of patients die within five years.

Currently, there is no biochemical screening test commercially available for RCC, but researchers found that the protein biomarkers were more than 95% accurate in identifying early-stage kidney cancers. In addition, there were no false positives caused by noncancerous kidney disease.

A second potential application of the biomarker test is in identifying which patients who have a mass in their kidney actually have cancer. “Having surgery to remove a kidney after a mass is found is the typical default treatment,” said Kharasch. But in about 10% to 15% of individuals, the mass can be noncancerous, “so testing a patient’s urine after a radiographic scan can further help identify whether a mass is cancer or not, and hopefully prevent the removal of a normal kidney.”

Kharasch and principal investigator Jeremiah J. Morrissey, PhD, professor of anesthesiology, analyzed urine samples from 720 patients at Barnes-Jewish Hospital who were about to undergo abdominal CT scans for reasons unrelated to a suspicion of kidney cancer. The researchers also analyzed samples from 80 healthy people and 19 patients previously diagnosed with kidney cancer.

The researchers measured the levels of AQP1 and PLIN2 in the urine and found that none of the healthy people had elevated levels of either protein. Patients with kidney cancer had elevated levels of both proteins.

In addition, three of the 720 patients who had abdominal CT scans, but were not known to have kidney cancer, also had elevated levels of both proteins. Two of those patients were diagnosed subsequently with kidney cancer, and the third patient died from other causes before a diagnosis could be made.

“Each protein, or biomarker, individually pointed to patients who were likely to have kidney cancer, but the two together were more sensitive and specific than either by itself,” said Morrissey in a statement. “When we put the two biomarkers together, we correctly identified the patients with kidney cancer and did not have any false positives.”

Even when patients had other types of noncancerous kidney disease, levels of the two proteins in the urine were not elevated and did not suggest the presence of cancer.

“Patients with other kinds of cancer or other kidney diseases don’t have elevations in these biomarkers,” said Kharasch. “So in addition to being able to detect kidney cancer early, another advantage these biomarkers may be capable of showing who doesn’t have the disease.”

Kharasch and Morrissey are working to develop an easy-to-use screening test for kidney cancer, much like mammograms, colonoscopies, or other tests designed to identify cancer at early, more treatable stages before patients have symptoms.

Licensing the technology and developing the assay would be the next steps, with eventual approval by the US Food and Drug Administration, said Kharasch.

“We hope that if the test becomes available, it will have a significant impact. Our goal is to improve health, advance public health, and reduce the 14,000 deaths caused by kidney cancer each year,” said Kharasch.

	Morrissey JJ, Mellnick VM, Luo J, et al. Evaluation of urine aquaporin 1 and perilipin 2 concentrations as biomarkers to screen for renal cell carcinoma. [Published online] 

. http://oncology.jamanetwork.com/article.aspx?articleid=2196180&resultClick=3. Accessed May 27, 2015

Two urine biomarkers, aquaporin 1 and perilipin 2, could be the key to the development of a simple urine test that leads to the detection of asymptomatic, early-stage kidney cancer.

June 2015 | Oncology Live Urologists in Cancer Care®

Grasp of Clinical Science Now a Necessity in Urologic Oncology

Urology Practice and Specialty Pharmacy Meet at a Crossroads

Specialty Pharmacy Makes Inroads in Urology Practice

Amnion/Chorion Wrap Improves Outcomes Following Robot-Assisted Prostatectomy

Progress in Immunotherapy Continues, But Pseudo-Progression Is a Concern

Simple Urine Biomarker Test Could Identify Early-Stage Renal Cell Carcinoma