PREDICT looking for predictive biomarkers in renal cell carcinoma

		The PREDICT (Personalized RNA Interference to Enhance the Delivery of Individualized Cytotoxic and Targeted Therapeutics) Consortium is conducting multicenter, single-arm phase II trials of everolimus (EPREDICT) or sunitinib (S-PREDICT) administered around the time of the nephrectomy in patients with untreated metastatic renal cell carcinoma (mRCC). Although inhibitors of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR) have transformed mRCC therapy, predictive biomarkers have not been identified. The researchers plan to analyze the molecular markers of paired biopsies before and after treatment and compare them to clinical data to find predictive biomarkers. Sunitinib and everolimus will be given before and after nephrectomy and will continue until disease progression at metastatic sites. The primary clinical endpoint is the safety of peri-nephrectomy everolimus and sunitinib. Secondary endpoints include efficacy and biomarker measurements. The researchers hope to recruit 60 patients per trial.

 section is intended to stimulate discussion about ongoing clinical trials and to promote collaboration across the urology community. In each issue, 

 presents summaries of ongoing research relating to a variety of urologic cancers.	

Everolimus alternating with sunitinib for renal cancer

 The University of Sydney; Novartis Australian New Zealand Clinical Trials Registry

	This phase II study is aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced renal cell carcinoma (RCC). Individuals are eligible provided they have RCC with a clear-cell component, metastatic or locally advanced disease not suitable for resection, ECOG performance status of 0-1, and low or intermediate Memorial Sloan- Kettering Cancer Center prognostic score. Treatment is administered in 12-week cycles consisting of 4 weeks of sunitinib (50 mg daily) followed by 2 weeks’ rest, followed by 5 weeks of everolimus (10 mg daily), followed by 1 week of rest. The primary endpoint is the status of being alive and progression- free by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria 6 months after enrollment. Participants who stop one drug because of toxicity or disease progression on or before the 6-month assessment will continue the other drug until subsequent progression or unacceptable toxicity on the second drug. 

Oral MDV3100 in chemotherapy-naïve patients with metastatic prostate cancer

Sunitinib or placebo for patients at high risk of recurrent renal cell cancer

		This phase III study is comparing sunitinib with placebo as adjuvant treatment in patients at high risk of recurrent kidney cancer per modified University of California Los Angeles Integrated Staging System (UISS) criteria after surgery. Subjects are Eastern Cooperative Oncology Group (ECOG) grade 0 to 2 and have predominant clear-cell histology. In addition, they have not undergone prior anticancer treatment but have had their kidney tumor removed with no evidence of macroscopic disease following surgery. Approximately 720 patients will be randomized to sunitinib 50 mg PO or placebo on a 4/2 schedule: 4 weeks on, 2 weeks off for 1 year or until disease recurrence or occurrence of a secondary malignancy, significant toxicity, or withdrawal of consent. The primary outcome measure is disease-free survival. Investigators will also determine overall survival, safety, tolerability, and patient-reported outcomes.

	This phase III study will test the efficacy and safety of the novel androgen signaling inhibitor MDV3100 in chemotherapy-naïve patients who have progressive metastatic prostate cancer despite androgendeprivation therapy (ADT) as defined by rising prostate-specific antigen levels or progressive soft-tissue or bony disease. Study participants are asymptomatic or mildly symptomatic from prostate cancer. The primary outcome measures are overall survival and progression-free survival. Secondary outcome measures are time to first skeletal-related event and time to initiation of cytotoxic chemotherapy. An estimated 1680 men will participate in the study, which has a targeted primary completion date of September 2014.	

Axitinib (AG-013736) for the treatment of metastatic renal cell cancer

		This phase III study is designed to determine whether axitinib is superior to sorafenib in delaying tumor progression in patients with metastatic renal cell cancer. Participants are required to have histologically documented metastatic renal cell cancer with a component of clear-cell histology and evidence of measurable disease. They cannot have received prior systemic first-line therapy or must have progressive disease per Response Evaluation Criteria In Solid Tumors (RECIST) - version 1.0 after one prior systemic first-line regimen for metastatic disease containing sunitinib, cytokine(s), or both. Subjects will be randomized to axitinib at a starting dose of 5 mg bid with continuous dosing or sorafenib at a dose of 400 mg bid with continuous dosing. The primary outcome measure is progression-free survival. Secondary outcome measures include overall survival, response rate, safety and tolerability, duration of response, kidney-specific symptoms, and health status.

Radiopharmaceuticals and zoledronic acid for bone metastases

		This phase III study is testing whether zoledronic acid, vitamin D, and calcium is superior to zoledronic acid, vitamin D, and calcium plus either strontium 89 or samarium 153 in the delaying of bone problems in patients with bone metastases from lung, breast, and prostate cancer. The primary outcome measure is the time to development of a malignant skeletal-related event (SRE). Secondary outcome measures include SRE at 1 year, overall survival, changes in quality of life, changes in pain control, and the utility and cost-effectiveness of the use of radiopharmaceuticals and bisphosphonates. The study is aiming to recruit about 352 patients, with an estimated primary completion date of March 2013.

Opioid titration order sheet or standard care in treating patients with cancer pain

		This phase III study is comparing the use of an opioid titration order sheet versus standard care for the management of cancer pain. An opioid titration order sheet allows healthcare providers to adjust the dosage and schedule of pain medication. The primary outcome measure is pain, including intensity, duration, and pain-related distress. Secondary outcome measures are function, mood, and quality of life. All participants have cancer-related pain and have received at least 1 week of fixed-dose opioid therapy and satisfy any of the following criteria: self-reported inadequate pain control; the need for two or more rescue doses per day; or the need for adjustments in their pain regimen involving either fixed or breakthrough dosing.		

American ginseng for cancerrelated fatigue

		This phase III study intends to determine whether the perennial American ginseng (also known as Panax quinquefolius) improves cancer-related fatigue. Subjects had been diagnosed with cancer within the past 2 years and had a history of cancer-related fatigue as defined by an average score of ≥ 4 over the past 30 days on the numeric analogue scale (1-10). Patients are stratified according to baseline fatigue score, disease status of current cancer, current treatment, duration of all prior cancer treatment in their lifetime, and current tumor type, after which they are randomized to receive oral American ginseng or placebo twice daily for 14 days. Treatment is repeated every 2 weeks for a total of 4 courses. The primary outcome measure is the duration of response as measured by the general subscale Multidimensional Fatigue Symptom Inventory— Short Form (MFSI-SF).

Adding custirsen for pain relief in advanced prostate cancer

		This phase III study is assessing the pain palliation benefit of adding the clusterin inhibitor custirsen to docetaxel retreatment or cabazitaxel as second-line chemotherapy in men with metastatic castration-resistant prostate cancer. Selection of the chemotherapy is to be determined by the treating physician based on the patient’s first-line response. The study’s main objective is to assess pain and analgesic use for the evaluation of durable pain palliation in response to the study treatment. Pain and analgesic use are determined via a third-party contact center. Secondary outcome measures include time to pain progression and safety. An estimated 292 patients will be recruited for the study.

 OncoGenex Technologies and Teva Pharmaceuticals USA

Articles

In each issue, Urologists in Cancer Care presents summaries of ongoing research relating to a variety of urologic cancers.

Urologic Trials in Progress

An international group of investigators provided first-time evidence of the impact of smoking on outcomes in bladder cancer in results from two studies that were reported at the 2012 Society for Urologic Oncology) annual meeting in Bethesda, Maryland. Both studies found significant increased risks of recurrence, disease progression, and survival with continued smoking after diagnosis and treatment for bladder cancer. The studies also quantified a timeframe for reduction of these risks to that of nonsmokers following smoking cessation.

	Smoking and Smoking Cessation in Primary Nonmuscle-Invasive Bladder Cancer (NMIBC)

Smoking has long been a known risk factor for bladder cancer, but a dose-response relationship has not previously been well described in the literature.

Smoking status and higher cumulative smoking exposure were linked to worse prognoses in 2043 patients with NMIBC who were treated with transurethral resection of the bladder with or without intravesical instillation therapy, as reported by Evanguelos Xylinas, MD, from Weill Cornell Medical College in New York City.

Smoking histories that were obtained from patients included an average number of cigarettes smoked per day (CPD); duration of smoking in years; and time since smoking cessation. Lifetime cumulative smoking exposure was designated in the following manner: light short-term as ≤19 CPD for ≤19.9 years; light long-term as ≤19 CPD for ≥20 years. Heavy short-term smoking exposure was defined as ≥20 CPD for ≤19 years; and heavy long-term smoking exposure was defined as ≥20 CPD for ≥20 years.

The results showed that cumulative smoking exposure among both current and former smokers was significantly associated with disease recurrence (

 <.001) in multivariate analysis. Heavy long-term smokers had the worst outcomes.

However, smoking cessation of greater than 10 years’ duration significantly reduced the risk of disease recurrence (hazard ratio [HR] = 0.66; 95% CI, 0.52-0.84; 

 <.001) and progression (HR = 0.42; 95% CI, 0.22-0.83; 

Another similar study, examining the impact of smoking and smoking cessation on outcomes in bladder cancer patients who were treated with radical cystectomy, produced some similar results.

		Table. Smoking-Related Outcomes in Primary Nonmuscle-Invasive Bladder Cancer

		CI indicated confidence interval; HR, hazard ratio.

An international group of investigators provided first-time evidence of the impact of smoking on outcomes in bladder cancer in results from two studies.

Studies Determine Smokers' Risks of Recurrence, Progression, and Survival in Bladder Cancer

The cornerstone of the Oregon Urology Institute (OUI) business model was kidney stones: In 1997, two separate practices, Oregon Urology Specialists and Urology Healthcare, joined forces to start a lithotripsy service.

“That joint venture helped build a lot of trust between our two practices,” explained Bryan Mehlhaff, MD, medical director of what is now known as OUI. “Then we started talking about building a clinic that we would own together. For a short period of time, we functioned as two parallel groups but practicing in the same space. Little by little, we started merging our billing, scheduling, and clinical functions… then formally merged into OUI.”

Headquartered in Springfield, Oregon, the practice boasts 15 physicians and five physician assistants. Its services include an imaging center, a surgery center, pathology lab, a physical therapy program, and a radiation center that is dedicated solely to prostate cancer treatment.

Although OUI is the dominant provider of urology care in the area, this large urology practice isn’t immune to the economic challenges in light of the recent changes in healthcare, such as the implementation of the Affordable Care Act (ACA), wrangling over the high cost of care, and meeting the demands of a growing patient population.

 spoke with Mehlhaff and retired physician Robert Litin, MD, about how OUI is adapting its well-established practice to an ever-shifting healthcare landscape.

The screening and treatment of prostate cancer has been the subject of intense debate and controversy in recent months. Many feel the field faltered when the US Preventive Services Task Force (USPSTF) came out with its recommendation in 2011 that healthy men should no longer have PSA measurements as a screening test for prostate cancer. However, tremendous strides have been made in the treatment of advanced prostate cancer, including the immunotherapy sipuleucel- T (Provenge) and the therapeutic agent abiraterone acetate (Zytiga). Despite the controversy in this area, Mehlhaff has strived to make a difference in the treatment of prostate cancer at OUI.

“I’ve been the champion of treating advanced prostate cancer in our group. It took a while to educate my partners on the new treatments and convince them that those patients don’t have to go straight to the oncologist. So I’ve made it a mission to help my group look at the treatment opportunities that we have here,” he said.

But these treatments come with significant price tags that may seem to put urology at odds with the current ethos of cost-cutting in healthcare. However, Mehlhaff pointed out that, unlike other cancers, therapeutic options in prostate cancer have come about at a slower pace.

“There hasn’t been as much development in prostate cancer as there has been in colon cancer or breast cancer, for example,” he said. “Both those disease states currently have a lot of very expensive, but effective, therapies associated with them. In some ways, we are just catching up in urology in terms of what we can offer prostate cancer patients. So at this point, these treatments seem very expensive, but if you compare it to the cost and efficacy of common treatments for other cancers, the costs are not out of the ballpark.”

Not that OUI advocates a “treat all comers” approach. “Our job here is to do what is best for our patients, and that doesn’t mean that every patient should get the most expensive and aggressive therapy,” Mehlhaff said. “I recently had a very elderly patient who expressed interest in Provenge. With his array of other medical problems, I didn’t feel he was an appropriate candidate for that treatment. Instead, we looked at oral therapies for him. I think using our clinical knowledge is the best way to implement cost control.”

But there is a concern that the USPSTF recommendations against routine PSA testing will send prostate cancer back to a time when men arrived at the urologist’s office with advanced-stage disease. Litin, who retired from OUI in 2012 after 59 years of practice, recalled a time when “watchful waiting” meant something very different in prostate cancer patients.

“There was a time where we’d perform the prostatectomy and then go to bed that night hoping that the patient made it to morning and didn’t bleed out,” Litin said. “It was that kind of a major operation. In addition, at that time, we had no idea of knowing whether the disease had spread. So that’s where PSA made some difference, although it gave us limited information. We didn’t have the PET scans and other tests back then."

With the passage of the ACA, it’s estimated that 30 million more Americans will join the ranks of those with some type of health insurance coverage by 2015.

For OUI, that will mean adding to their already full plate. “We are essentially the only provider of urologic services in our county,” Mehlhaff said. “The only procedure that we don’t do here is kidney transplants, but all the other urologic cases come to us. So we know that we are already meeting the needs of our patients, and we believe that we’ll continue to do that with this potential pool of new patients.”

One way to manage these patients is, when appropriate, enrolling them in a clinical trials program. Some of the trials that the practice is now involved in are:

		A phase II, randomized efficacy study of enzalutamide (Xtandi) versus bicalutamide (Casodex) in men with prostate cancer who have failed primary androgen-deprivation therapy

		A phase II, randomized evaluation of DN24-02 as adjuvant therapy in subjects with high-risk HER2-positive urothelial carcinoma

OUI also maintains its leadership position in urologic care through its Oregon Urology Foundation. This nonprofit arm of the practice bestows grants in the range of $10,000 to $25,000 to other nonprofit advocacy organizations, such as Volunteers in Medicine, a clinic that provides free medical care to uninsured working adults in Deschutes County, and Friends of Florence, a group that arranges transport of cancer patients from small towns to the Springfield/Eugene area for treatment.

The foundation also sponsors free prostate cancer screening events, which are funded through a Father’s Day Prost8K run/5K walk. In addition, the group hosts a professional continuing medical education program, the Oregon Urology Symposium, for primary care providers in the region.

In 2012, the foundation, in conjunction with Lane Community College in Eugene, Oregon, created the Olof E. Sohlberg, MD, Memorial Scholarship. The $50,000 endowment will fund annual scholarships for students in the college’s nursing program.

Mehlhaff credits Sohlberg, a senior partner in OUI who passed away in 2011, with pushing the practice outside of the exam room and into the community.

“He was a great champion of doctors getting out and being active members of the community, encouraging them to see that it wasn’t enough to just practice,” Mehlhaff said. “We have a successful practice, and we want to give back to the community. It’s not just about being a good physician; it’s about making a difference in the bigger picture.”

An interview with Bryan Mehlhaff, MD, and retired physician Robert Litin, MD, about how Oregon Urology Institute is adapting its well-established practice to an ever-shifting healthcare landscape.

Blazing the Oregon Trail: Oregon Urology Institute Nurtures Its Position as a Urology Care Leader

Active surveillance (AS) is an emerging primary management strategy for men with lower-risk, localized prostate cancer. At intermediate follow-up (median, 52 months), investigators from the University of California at San Francisco (UCSF) AS program found that treatment can safely be delayed in patients who are carefully selected but then demonstrate disease progression after a period of AS. Five-year prostate-cancer-specific survival was 100% and overall survival was 98%.

Allison Glass, MD, and Peter Carroll, MD, presented these data on behalf of their co-investigators at the 2012 Society of Urologic Oncology annual meeting, in Bethesda, Maryland.

For the analysis, 691 of 1000 men who are currently in the UCSF AS program provided consent for the analysis. Two-thirds of the men in the cohort met the institution’s strict AS criteria, which included: ≤T2, PSA <10 ng/mL, Gleason score ≤6 without pattern 4 or 5, ≤ 33% diagnostic biopsy cores cancer-positive, and ≤50% single core with cancer involvement.

Clinical risk at diagnosis was defined using the UCSF Cancer of the Prostate Risk Assessment (CAPRA) score, and surveillance monitoring conformed to the UCSF AS Protocol (

		Table. UCSF Active Surveillance Protocol

		DRE indicates digital rectal exam; PSA, prostate-specific antigen; UCSF, University of California, San Francisco.

Ninety-three percent of enrolled patients were Caucasian, with a mean age of 62.2 ±7.9 years. Two-thirds had T1 disease. At baseline, 84% had a low (0-2) CAPRA risk score; 15% had an intermediate (3-5) score.

Of the 81% (563) of patients who underwent one or more repeat biopsies, 37% (206) had an increase in Gleason score, and 22% (123) had increased volume in more than 33% of positive cores. Thirty-six percent of the cohort underwent delayed intervention. For this group, treatment-free survival at 5 years was 62%. Twentytwo percent underwent radical prostatectomy (RP); 10% received radiotherapy, and 4% were prescribed androgen-deprivation therapy. Gleason upgrade was found to be the strongest predictor of delayed RP (hazard ratio = 3.8; 95% CI, 2.8-5.1; 

The rate of delayed treatment in this study cohort, according to the investigators, is similar to that of other institutions, and is most often precipitated by grade migration.

As a primary management strategy for men with lower-risk prostate cancer, Glass indicated that AS represents a “significant shift in the field.” A growing consensus supports its use for men with low-risk prostate cancer. But its adoption is significantly lagging behind medical opinion. “It is estimated that only about 10% of men who are candidates will choose active surveillance in this country,” said Glass. In Europe this figure is about 30%— higher, but still behind the evidence.

Younger men especially choose to undergo radical intervention, potentially enduring treatment-related effects that can severely impact quality of life. Many of these men will never have symptoms of the disease or die. The authors noted that they did not see any worse outcomes in the men in the original cohort who did not meet the strict UCSF criteria for AS. Men who had delayed surgery experienced similar rates of adverse pathologic findings and biochemical recurrence compared with those who underwent immediate surgery.

“The big message from our data is that, at an intermediate follow-up (52 months), active surveillance appears to be a safe primary management strategy for men with lower-risk disease,” the authors concluded. 

Treatment can safely be delayed in patients with low-grade prostate cancer who are carefully selected but then demonstrate disease progression after a period of active surveillance.

Active Surveillance Safe Primary Management Strategy for Patients With Low-Grade Prostate Cancer

: This article was developed as a result of a collaboration between members of the Division of Urologic Oncology at Columbia University Medical Center, James F. McKiernan, MD, and Jennifer Ahn, MD, and our freelance writer, Barbara L. Jones.

	Management of nonmuscle-invasive bladder cancer (NMIBC) remains difficult, with high rates of recurrence and disease progression despite strict surveillance, local resection, and intravesical therapy. About 50% of patients experience disease recurrence within 5 years even with the most effective current treatment—intravesical bacillus Calmette-Guérin (BCG).

	In a featured presentation at the 2012 Society of Urologic Oncology annual meeting in Bethesda, Maryland, James M. McKiernan, MD, director of Urologic Oncology at Columbia University in New York City, reviewed treatment alternatives under study for NMIBC, but pointed to a context characterized by nonstandardized study frameworks and a lack of creative collaborations that could result in truly novel treatments capable of producing better outcomes for patients.

	Also, the heterogeneous nature of BCG failure makes it difficult to assess efficacy of new drugs. Study populations are often mixed, consisting of patients differing by timing of the BCG failure, presence or absence of carcinoma in situ, lymphovascular invasion, micropapillary features, and tumor stage.

	Definitions of failure have been proposed, depending on the initial response to BCG and timing of recurrence, McKiernan said. But these have yet to be uniformly adopted into practice.

	At present, however, multiple intravesical agents are under investigation, primarily for patients who have failed BCG therapy.

	One strategy to address recurrence after BCG is the intravesical use of chemotherapeutic agents, which are used systemically for urothelial cancer:	

			Intravesical gemcitabine has been shown to be well tolerated, and results of a recent phase II study (SWOG S0353) showed moderate efficacy with 13/47 (28%) patients showing no evidence of disease at 12 months follow-up.

 This study enrolled patients with at least two prior courses of BCG and kept patients who responded after 6 weeks on monthly maintenance up to 12 months.

			Intravesical taxanes have also shown similar efficacy, particularly with added drug delivery technology, including binding paclitaxel to hyaluronic acid (ONCOFID-P-B) or albumin.

 A phase I study of ONCOFID-P-B demonstrated a 60% (9/16) response rate in patients with BCG-refractory carcinoma in situ.

	An ongoing phase II study of nanoparticle albumin-bound paclitaxel (Abraxane) currently has a complete response rate of 27% (7/26) at 11 months follow-up, similar to gemcitabine. An alternative strategy is to employ a multidrug regimen, as is standard with systemic chemotherapy.	

			The combination of gemcitabine and mitomycin C has resulted in a 3-month complete response rate of 60% (6/10).

			Combining mitomycin C, doxorubicin, and cisplatin has also been reported.

 This approach is promising, said Jennifer Ahn, MD, postdoctoral residency fellow in urology at Columbia University, New York City, as patients may have an increased chance of responding to at least one of the agents in the multidrug regimen, improving the overall response rate. However, further research in this area is certainly needed, and Ahn and McKiernan are currently collaborating to develop a novel new strategy to deliver multiple new compounds intravesically in humans.

	BCG is not a chemotherapeutic agent, but an immunotherapy. Therefore, multiple agents have been developed to adopt this mechanism.	

			Mycobacterial cell wall DNA complex (MCC) uses elements of BCG to elicit an immune response but does not contain live vaccine, thus reducing infectious and inflammatory complications. MCC is well tolerated, and has exhibited a 46% complete response rate at 26 weeks in a phase II trial.

 (A phase III randomized trial was recently closed due to poor accrual.)

			Oportuzumab monatox is a treatment employing Pseudomonas exotoxin A to induce cell death, aided by fusion to the anti-EpCAM antibody, which enables preferential binding to urothelial cells. A recently published phase II study exhibited a complete response rate of 16% at 24 months.

			Another targeted therapy, CG-0070, uses an adenovirus that targets retinoblastoma (Rb) defective cells, a common mutation in urothelial carcinoma, and transfects granulocyte- macrophage colony-stimulating factor (GM-CSF), causing local cytotoxicity. Patients with Rb mutations exhibited an 80% response rate, compared with 49% overall.

	As more is understood regarding pathogenetic changes of bladder cancer, McKiernan and Ahn predict that targeted therapies and multidrug regimens will likely be a robust area of research and development. Still, at this time no agent is reliably superior to the rest. And, McKiernan noted that small cohorts, heterogeneous study populations, and various response rates complicate the interpretation.

	Collaborative and standardized efforts to develop and evaluate novel drugs are necessary to ultimately provide effective long-term treatment for this high-risk, complicated population.	

				Skinner EC, Goldman B, Sakr WA, et al. 1666 SWOG S0353 phase II trial of intravesical gemcitabine in patients with non-muscle invasive bladder cancer who recurred following at least two prior courses of BCG. 

				McKiernan JM, Barlow LJ, Laudano MA, et al. A phase I trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer. 

				Tringali G, Lisi L, Bettella F, et al. The in vitro rabbit whole bladder as a model to investigate the urothelial transport of anticancer agents: the ONCOFID-P paradigm. 

				Breyer BN, Whitson JM, Carroll PR, Konety BR. Sequential intravesical gemcitabine and mitomycin C chemotherapy regimen in patients with non-muscle invasive bladder cancer. 

				Chen CH, Yang HJ, Shun CT, et al. A cocktail regimen of intravesical mitomycin-C, doxorubicin, and cisplatin for non-muscle-invasive bladder cancer. 

				Morales A, Phadke K, Steinhoff G. Intravesical mycobacterial cell wall-DNA complex in the treatment of carcinoma in situ of the bladder after standard intravesical therapy has failed. 

				Kowalski M, Guindon J, Brazas L, et al. A phase II study of oportuzumab monatox: an immunotoxin therapy for patients with noninvasive urothelial carcinoma in situ previously treated with bacillus Calmette-Guérin. 

				Burke JM, Lamm DL, Meng MV, et al. A first in human phase I study of CG0070, a GMCSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. 

Collaborative and standardized efforts to develop and evaluate novel drugs are necessary to ultimately provide effective long-term treatment for nonmuscle-invasive bladder cancer.

Targeted Therapies, Multidrug Regimens, and Standardized Drug Development Efforts Needed in Nonmuscle-Invasive Bladder Cancer

 Although the 2009 American Urological Association (AUA) guidelines cite “compelling data” for consideration of nephron-sparing surgery in all patients, partial nephrectomy remains underutilized for small renal masses, according to a new analysis.

At the 2012 Society of Urologic Oncology (SUO) annual meeting in Bethesda, Maryland, Marc Bjurlin, MD, clinical instructor in the Department of Urology at New York University, reported findings from an analysis of the use of partial nephrectomy before and after issuance of the 2009 AUA guidelines. For management of clinical stage 1 renal masses, the guidelines state that partial nephrectomy provides equivalent oncologic outcomes for the treatment of small renal masses and minimizes the risk for chronic kidney disease, associated cardiovascular disease, and mortality over the longer term.

Bjurlin and colleagues analyzed data from the Nationwide Inpatient Sample between 2007 and 2010. The dataset includes a 20% sample of all US inpatient hospitalizations.

The investigators identified 26,224 patients with renal tumors who underwent surgery. Prior to the guidelines, 27% (4033) of patients underwent partial nephrectomy. After the guidelines were issued in 2009, 32% (3560) received partial nephrectomy for small renal masses. On multivariate analysis, undergoing surgery after the issuance of the AUA guidelines was an independent predictor of partial nephrectomy (odds ratio [OR] =1.28; 95% CI, 1.21-1.36; 

Other factors associated with use of partial nephrectomy included urban location, surgery that was conducted at a teaching hospital, large-hospital status, location in the Northeast, and black race. Gender and chronic kidney disease were not associated with partial nephrectomy.

		Figure. Partial Nephrectomy Use Before and After the Introduction of the 2009 AUA Guidelines

Although the study did not look at barriers to partial nephrectomy, several have been suggested, Bjurlin said, including patient decision, tumor characteristics, the hospital where the surgery is performed, and surgeon characteristics. Increased comorbidities have also been shown to reduce the likelihood of choosing a partial nephrectomy. “Tumor size and complexity often drive a decision for a partial nephrectomy,” he said. The investigators also observed that age was a barrier.

A suboptimal adoption trend following a clinical guideline change could be overemphasized, however. Other surgical disciplines have had less success with the impact of their guidelines— cardiology and obstetrics/gynecology, for example, Bjurlin said. Even so, he suggested that the barriers need to be individually addressed in order to bring about wider adoption of use of partial nephrectomy in the urology community.

“The take-home message is that even though the adoption of partial nephrectomy increased after the establishment of the AUA guidelines for renal masses, partial nephrectomy remains underutilized,” Bjurlin said. “Our focus now needs to be on these barriers to adoption of partial nephrectomy and how to overcome them.”

Although the 2009 AUA guidelines cite "compelling data" for consideration of nephron-sparing surgery in all patients, partial nephrectomy remains underutilized for small renal masses.

February 2013 | Special Issues

Urologic Trials in Progress

Studies Determine Smokers' Risks of Recurrence, Progression, and Survival in Bladder Cancer

Blazing the Oregon Trail: Oregon Urology Institute Nurtures Its Position as a Urology Care Leader

Active Surveillance Safe Primary Management Strategy for Patients With Low-Grade Prostate Cancer

Targeted Therapies, Multidrug Regimens, and Standardized Drug Development Efforts Needed in Nonmuscle-Invasive Bladder Cancer

Partial Nephrectomy Remains Underutilized, Despite AUA Endorsement