Aine Cryts is a freelancer based in Boston. She is a frequent contributor to Managed Healthcare Executive on topics such as diabetes, oncology, hospital admissions and readmissions, senior patients, and health policy.

Aine Cryts

Although monopolar transurethral resection of the prostate (TURP) remains the standard of care for bladder outlet obstruction secondary to BPH, its utilization has decreased in recent years, according to a recent study.

TURP is the standard of care for BPH in prostates under 80 mg, according to guidelines from the AUA and other international groups, but new approaches such as GreenLight Laser photoselective vaporization of the prostate (PVP), holmium laser ablation of the prostate (HoLAP), and holmium laser enucleation of the prostate (HoLEP) are increasingly being performed in the treatment of BPH.

Until recently, few studies have evaluated the perioperative outcomes of these procedures in the inpatient setting, said Christian P. Meyer, MD, a urologist at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, in his presentation at the 2017 AUA annual meeting in Boston.

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For their research, Dr. Meyer and colleagues accessed the 

, an all-inpatient database representative of 20% of all U.S. hospital admissions, and looked at a cohort of approximately 140,000 patients who underwent monopolar TURP, bipolar TURP, or GreenLight Laser PVP for BPH. The timeline was from 2003 to 2013, and the research covered almost 450 hospitals across the United States. A range of inpatient settings, such as community hospitals and academic centers, was included in the study.

The research entailed searching the charge description master file to identify specific supply codes unique to each endoscopic procedure in order to identify them appropriately. Under evaluation were 90-day postoperative complications, operating room time, hospital length of stay, and indirect hospital costs. Also factored into the analyses were patient, hospital, and surgeon characteristics, Dr. Meyer said.

In terms of 90-day direct hospital costs, Dr. Meyer said that when bipolar and monopolar TURP were compared, bipolar TURP cost almost $1,000 more.

The GreenLight Laser PVP cost almost $1,500 more than monopolar TURP.

Dr. Meyer observed that while monopolar TURP continues to be the standard of care for the treatment of BPH, he and colleagues observed a decreasing trend for the use of monopolar TURP, from 100% in 2003 to 78% in 2013. Further, the data showed an increasing trend for the use of procedures other than TURP to almost 11% in 2013.

When comparing bipolar and monopolar TURP, there was almost no difference in terms of operating room time, Dr. Meyer said. There was no difference in length of stay or 90-day complication rates, with borderline significance for urinary urgency favoring bipolar TURP. When compared with monopolar TURP, GreenLight Laser PVP procedures typically lasted 12 minutes longer than the full cohort, which is significant, he added. Still, the length of stay for the GreenLight Laser PVP patients was significantly shorter.

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Because of the aging U.S. population and its high comorbidity profile, Dr. Meyer said focusing on procedures performed in an inpatient setting was appropriate, since these procedures will likely be performed in inpatient settings in the future.

He reported that the use of monopolar TURP has decreased significantly since the start of the study in 2003, but it’s still the standard of care for better surgical outcomes in the inpatient setting.

GreenLight Laser PVP was also associated with fewer cases of dilutional hyponatremia and prostatic complications such as structural fistula infarction and prostatic adhesions, added Dr. Meyer.

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Articles

Although monopolar transurethral resection of the prostate remains the standard of care for bladder outlet obstruction secondary to BPH, its utilization has decreased in recent years, according to a recent study.

Study: Monopolar TURP utilization on the decline

Treatment of lower urinary tract symptoms/BPH with convective water vapor ablation (Rezum System) appears to provide significant improvement on two key outcome measures versus medical therapy at up to 2 years, according to a study presented at the AUA annual meeting in Boston.

	The study compared water vapor ablation therapy with medical therapy based on a historical cohort from the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Findings were presented by first author Nikhil K. Gupta, MD, who was with Southern Illinois University School of Medicine in Springfield at the time of the study.

Dr. GuptaMinimally invasive surgical therapies have aimed to “thread the needle” between surgical and pharmacologic options, said Dr. Gupta, who is currently assistant professor of urology at Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.

	“The daily grind of taking pills is an underappreciated barrier to treatment, especially for the average BPH patient who is older and likely has comorbidities requiring treatment. Symptom relief without increasing medication burden or affecting sexual function can significantly improve quality of life for our patients and can have a real impact on BPH treatment patterns moving forward,” Dr. Gupta told 

	Rezum uses convection energy in the form of water vapor, which distributes itself evenly within the treated tissue while remaining within collagen barriers and causing a uniform cell necrosis. According to previously published data, the treatment delivers durable symptom relief with minimal sexual side effects.

	When looking at the effect of medical therapies for BPH, the MTOPS study is considered the gold standard, he said. In three treatment arms of the trial, patients received an alpha-blocker, a 5-alpha-reductase inhibitor, or a combination of both. As there is no reliable contemporary cohort, Dr. Gupta pointed out that the high-quality MTOPS trial provides a “reliable, historical medical therapy cohort” for comparing outcomes of BPH treatments.

	In the current study, results of the Rezum II trial 

 were compared with the three treatment arms of the MTOPS trial. For uniformity, Dr. Gupta and colleagues limited their focus to patients with prostate volume of at least 30 mL and International Prostate Symptom Score (IPSS) of at least 13.

	Standard clinical outcomes measures were used in this study, and comparisons were performed at 3 months, 6 months, 1 year, and 2 years. In addition, propensity score weighting was used to eliminate differences in IPSS, quality of life, and prostate volume between the groups at baseline.

	In looking at the outcomes, patients treated with the Rezum System showed greater improvement in IPSS and BPH impact index than those receiving the alpha-blocker at 2 years. In addition, Rezum appeared to result in a greater maximum flow rate (Qmax) than alpha-blockers, but this didn’t reach statistical significance and there was no clear pattern that emerged when comparing post-void residual volume.

	When comparing Rezum and the 5-alpha-reductase inhibitor cohort, Rezum showed significantly greater improvements in IPSS and BPH impact index than the 5-alpha-reductase inhibitor over 2 years, Dr. Gupta said. When comparing Rezum with combination medical therapy, IPSS and BPH impact index were similar at 2 years. Rezum improved Qmax as versus combination therapy at 1 year, with medical therapy catching up at 24 months. Combination therapy improved post-void residual volume to a greater extent than Rezum, he added.

	“Though flow rate and short-term symptom improvement are encouraging, 3-, 5-, and 10-year data will dictate whether the procedure will remain a part of the urologist’s armamentarium,” Dr. Gupta said.

	One of Dr. Gupta’s co-authors is an investigator and meeting participant/lecturer for NxThera, Inc. Several study co-authors have a financial and/or other relationship with one or more pharmaceutical companies.

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	In a 2012 paper, researchers from RAND Corp. called clinical practice guidelines “one of the foundations of efforts to improve health care” 

 The pace of modern medical advances underscores the importance of published clinical guidance, and has in fact led to an increase in the speed of guideline development and updates. The field of genitourinary cancer is no stranger to this trend.

	This article highlights the key points of two urologic cancer guidelines (which provide evidence-based guidance) and two consensus statements (which provide consensus recommendations by a multidisciplinary panel of experts) that have been published in the past year. The guidelines discuss nonmuscle-invasive bladder cancer and small renal masses, while the consensus statements examine immunotherapy for renal cell carcinoma and prostate cancer.

	Nonmuscle-invasive bladder cancer (AUA/SUO)

	The 2016 American Urological Association/Society of Urologic Oncology guideline on the diagnosis and treatment of nonmuscle-invasive bladder cancer (NMIBC) provides clinicians with a risk-stratification approach to treating this condition. The full guideline was published in 

Dr. ChangDepending on the patient’s unique experience with NMIBC, sometimes more follow-up and surveillance are warranted, whereas with other patients, their clinical teams should be mindful about when it’s more appropriate to “back off,” says Sam S. Chang, MD, professor of urologic surgery and urologic surgeon/oncologist at Vanderbilt University, Nashville, TN, who helped develop the guideline.

	Leveraging a risk-stratified approach, the guideline puts patients into one of three categories: low, intermediate, and high risk. The guideline’s treatment algorithm incorporates the tumor’s characteristics while factoring in the individual patient’s response to therapy. Attempting to help clinicians evaluate and treat individual patients, the guideline includes 38 statements, which rely on a variety of evidence.

	During diagnosis, specifically, the guideline recommends that clinicians perform a thorough cystoscopic examination of the patient’s entire urethra and bladder, in addition to evaluating and documenting the size, location, configuration, number, and mucosal abnormalities of the tumor. Experts also recommend that during the initial diagnosis, a complete visual resection of the bladder tumor(s) should be performed, in addition to imaging of the patient’s upper urinary tract.

	For a patient who has been treated for NMIBC in the past and has normal cystoscopy and positive cytology, prostatic urethral biopsies and upper tract imaging, in addition to enhanced cystoscopic techniques, such as blue light cystoscopy, should be considered.

	Also, in a patient with suspected or known low- or intermediate-risk bladder cancer, a single postoperative instillation of intravesical chemotherapy, such as mitomycin C or epirubicin, should be considered within 24 hours of transuretheral resection of a bladder tumor. For patients at intermediate risk-those who completely respond to induction bacillus Calmette-Guerin (BCG)-their clinical team should consider maintenance BCG for 1 year, as tolerated by the patient. In addition to recommendations on BCG relapse, salvage regimens, and other aspects of management, the document also provides risk-adjusted surveillance and follow-up strategies.

Dr. RussoIt wasn’t until the 1990s that kidney preservation in patients with small renal masses started to take hold, largely at Memorial Sloan Kettering Cancer Center, Mayo Clinic, and Cleveland Clinic in the United States and by health care providers in Europe. At Memorial Sloan Kettering in New York, urologic surgeon Paul Russo, MD, contrasts the number of kidney-sparing operations his team did each year when he was a fellow in the late 1980s-three total-with the three he performed on a recent day.

	That’s when a consensus started to develop around the positive outcomes patients could experience if only the tumor was removed and the kidney was spared, a decision that’s predicated by the size of the tumor and its location in the kidney, Dr. Russo says. He notes that 70% of cancerous masses found in the kidney are considered small-4 cm or less-and the vast majority of these are amenable to partial nephrectomy.

	Even a stage T1b tumor-at 7 cm or less-is still relatively small, adds Dr. Russo, who helped develop the American Society of Clinical Oncology’s clinical practice guideline on management of small renal masses, which was published earlier this year 

 (Approximately 30% of cancerous masses found in the kidney are considered large and/or metastatic.)

	Partial nephrectomy is the recommended treatment in patients whose tumor measures 4 cm or less. The guideline recommends radical nephrectomy only in instances where the tumor is significantly complex and not technically amenable to a kidney-sparing approach. Further, patients who develop progressive chronic kidney disease-in particular, proteinuria and/or a glomerular filtration rate of less than 60 mL/min/1.73 m2-should receive a referral to a nephrologist.

	Biopsy is best utilized in patients with a small renal mass when the results could alter management. In contrast, patients with significant comorbidities and limited life expectancy with a small renal mass are better candidates for active surveillance, and biopsy in that setting can be omitted.

	The guideline authors note that for patients with significant comorbidities and limited life expectancy, active surveillance is the appropriate response for initial treatment. The reasoning behind this recommendation is many of the asymptomatic masses found in patients over 70 years of age are often relatively indolent with limited metastatic potential and unlikely to threaten the patient during their remaining lifetime. In addition, the competing comorbidities, taken alone or together, are far more life threatening in the near term.

Next: Immunotherapy for treatment of RCC (Society for Immunotherapy of Cancer)

	Immunotherapy for treatment of RCC (Society for Immunotherapy of Cancer)

Dr. RiniA subset of patients with metastatic kidney cancer may not need immediate treatment, says Brian Rini, MD, medical oncologist at the Cleveland Clinic Taussig Cancer Institute and professor of medicine at the Cleveland Clinic Lerner College of Medicine. That point, along with recommendations on the use of newer immunotherapy agents and older drugs, is outlined in the Society for Immunotherapy of Cancer’s consensus statement on immunotherapy for the treatment of renal cell carcinoma (RCC), which was published last year in the 

	Since clinicians are trying to provide patients with the most benefit with the least amount of risk, that sometimes means not treating RCC patients-or certainly not treating them immediately, says Dr. Rini, the consensus statement’s first author. This is the appropriate treatment approach for patients who have very indolent disease that’s not bothering them. An additional benefit of this approach is that sometimes simply watching patients for a period of time can delay side effects while not compromising the benefit of ultimate treatment, he adds.

	While interferon-alpha and interleukin-2 have been used for decades with positive results, new immunotherapy agents for the treatment of renal cell carcinoma have been approved, according to the consensus statement. These new agents prevent tumor growth by preventing vascular endothelial growth factors in addition to tumor metabolism. Immune checkpoint inhibitors, the newest class of immunotherapy agents, should also have an impact on patients with RCC.

	According to the consensus statement, observation or enrollment in a clinical trial based on Level A evidence for cytokines and Level A evidence from the ASSURE clinical trial are the most appropriate treatment paths for patients with resected stage II and III renal cell cancer. Members of the task force that developed the statement agreed that nephrectomy is an important component of managing patients with renal cell carcinoma; further, the resection of oligometastases is supported, but it’s unclear how novel immunotherapy could impact these surgical approaches.

	There was division among task force members on the role of high-dose interleukin-2 in treating metastatic RCC. The overall opinion was that appropriate patients who have undergone a nephrectomy should discuss interleukin-2 with their clinicians and then receive a referral to a center of excellence for further discussion of treatment options. Sixty-seven percent of the experts agreed that a discussion about interleukin-2 was appropriate, while the remaining members said it was more appropriate for clinicians to select patients for these types of conversations.

	In addition to outlining new therapeutic agents and different approaches to patients, and incorporating immunotherapy into the routine management of kidney cancer, which is only just starting, Dr. Rini says this guideline “is really setting the stage for what’s to come as much as it is about taking care of patients now.”

Next: Immunotherapy for treatment of prostate carcinoma (Society for Immunotherapy of Cancer)

	Immunotherapy for treatment of prostate carcinoma (Society for Immunotherapy of Cancer)

Dr. GulleyThe Society for Immunotherapy of Cancer’s consensus 2016 statement on immunotherapy for the treatment of prostate carcinoma provides a framework to inform clinicians about which patients are most appropriate for immunotherapy and which patients are not appropriate for such a treatment path, says James L. Gulley, MD, PhD, director of the Medical Oncology Service with the National Institutes for Health’s Center for Cancer Research, who contributed to the consensus statement. The consensus statement was published in the 

	Still, Dr. Gulley points out that the consensus statement doesn’t say specifically which immunotherapy will work for individual patients. Rather, it provides guidance for the type of patients that he and other prostate cancer experts believe are most likely to benefit. Thus, not every patient is going to be an appropriate candidate for immunotherapy, he says.

	According to the consensus statement, immunotherapy is indicated for metastatic castration-prone cancer in patients with minimal or no symptoms. After reviewing the available studies, the experts found that the quartile of patients who received sipuleucel-T (Provenge) versus placebo earliest in the disease process lived an average of 13 months longer and experienced a 50% decrease in the chance of death. Patients in more advanced stages of the disease who received sipuleucel-T versus placebo gained an increase of 2 months and experienced a 20% reduction in the chance of death.

	As a group, the consensus panel experts state a reluctance to treat patients with rapidly progressing disease or significant visceral disease, such as liver metastasis. That’s because there was no dramatic decrease in the volume of the tumor or a decrease in prostatic ductal adenocarcinoma with sipuleucel-T treatment. Dr. Gulley says that’s likely because of the long-term effect of developing an adequate immune response during earlier stages of the disease. If clinicians believe they will run into problems earlier clinically, then they should pursue other treatments; a plurality of the experts said they would use agents like enzalutamide (XTANDI) in addition to sipuleucel-T, according to Dr. Gulley.

 Full disclosure of the guideline and consensus panel members’ conflicts of interest is provided in the published versions of the statements: 

This article highlights the key points of two urologic cancer guidelines (which provide evidence-based guidance) and two consensus statements (which provide consensus recommendations by a multidisciplinary panel of experts) that have been published in the past year.

Aine Cryts

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