Urology Times Co-Editor-in-Chief Michael S. Cookson, MD, MMHC, provides an in-depth preview of the 2021 American Urological Association Annual Meeting, covering the areas of prostate, bladder, and kidney cancer.

2021 AUA Annual Meeting Preview: Prostate, Bladder, and Kidney Cancer

 discusses the unmet need for a preventive treatment for patients with recurrent urinary tract infections (UTIs). At the 2021 AUA Annual Meeting, Nickel shared results from the groundbreaking study, "“

A novel sublingual vaccine will dramatically alter the clinical management of recurrent urinary tract infections in women

Nickel is a professor of the department of urology at Queen’s University and urologist at Kingston and Hotel Dieu General Hospitals, Kingston, Ontario, Canada.

Videos

“We have the rising spectra of national and international antibiotic resistance, which is becoming a huge international medical issue,” says J. Curtis Nickel, MD.

Novel MV140 vaccine is “game changing” for recurrent UTIs

Kidney stones are a common condition in urologic patients, resulting in high rates of morbidity. As obesity numbers increase around the world, many urologists wonder whether kidney stones can be prevented and if so, what patients can do to help inhibit the stone-forming process.

At the 2021 American Urological Association annual meeting, 

presented the John K. Lattimore Lecture, “Kidney Stones: Is Prevention Possible?” In his presentation, he discussed innovations in the medical management of recurrent nephrolithiasis. Preminger is Professor of Urologic Surgery and Director of the Comprehensive Kidney Stone Center at Duke University Medical Center, Durham, North Carolina.

How much of your time with patients is spent discussing prevention of stones?

Our practice primarily involves management of stones, and while we spend a considerable amount of time with endourologic stone removal, at least 50% of our time is spent with evaluation and ultimately, the medical prevention of our patients with stone disease. Even in patients that have only been single stone formers, especially those that have required surgical stone removal, we believe that medical stone management is warranted to prevent recurrent stones.

What are the challenges to preventing stones?

The challenges involved in medical stone prevention are first, making the diagnosis with current protocols. It's relatively easy if we can get the patient to perform two random 24-hour urine collections. Second, the hardest part is having the patient sign on to the program to increase their fluids, to potentially change their diet and, in the majority of individuals, to start them on medical therapy. And so, compliance with the regimen of both conservative measures and selective medical therapy is the hardest part of medical stone management. But once the patient is compliant with our treatment plan, and we can build these recommendations into their normal routine, we find that this form of selective medical stone management is not a significant burden for the patient.

How has your stone practice evolved over the past 3 to 5 years? What advances do you anticipate in the next 3 to 5 years?

Our practice has evolved in that many of the urologists in the community and out in practice are now a lot more familiar with medical stone evaluation and selective medical management. So, we find that the "routine stone formers" are now being managed out in the community, and our practice primarily deals with somewhat complicated patients, both surgical and medical. From a medical standpoint, these will be individuals who have been started on medical therapy and have not responded. We find that with some “fine tuning” of their medical management, we can usually get their stone disease under control.

From a future standpoint, one of the exciting things now in medical stone management has to do with the genomic evaluation of patients with stone disease. We're now finding that certain patients, such as those with renal tubular acidosis, cystinuria, or hyperoxaluria might have a monogenic cause of their stone disease. There are some very exciting studies that are currently underway, demonstrating the ability to genetically modify our patients’ risks for recurrent stone formation.

Is there a multi-specialty component to stone prevention? If so, what is the ideal way this should work?

For complete stone prevention, there needs to be a multi-specialty or a multi-disciplinary approach in that we need to treat the patients both surgically and medically if we want to prevent recurrent stones. At our institution, urology controls both the surgical management and medical stone prevention, but this would be something dependent upon the situation at your particular hospital, whether you have the expertise or the interest to do the medical evaluation and prevention of your patients with recurrent stones, or whether you employ the help of mineral metabolism, nephrology, or another group, perhaps dietary individuals. So, I believe you need to treat your patients with stones, both medically and surgically, and depending upon your expertise, that will determine how multi-disciplinary your stone prevention practice becomes.

Articles

"The challenges involved in medical stone prevention are first, making the diagnosis with current protocols," says Glenn M. Preminger, MD.

Stone prevention and advancements in stone practices

® Assistant Editor Janelle Hart spoke with 

 He discusses how his new technology, The PrecisionPoint Transperineal Access System, is used for detecting prostate cancer in patients. Matthew J. Allaway, MD, is the founder and president of Perinealogic and a urologist and managing partner at Urology Associates, Cumberland, Maryland.

Podcasts

“We need to do a better job sampling the prostate,” says Matthew J. Allaway, MD.

Dr. Allaway on the increased efficiency of transperineal biopsies

discusses the background and findings of the study, “MRI-guided focused ultrasound (MRgFUS) focal therapy for intermediate-risk prostate cancer: final results of a phase IIb multicenter study,” 

presented at the 2021 American Urological Association annual meeting

. Ehdaie is an assistant member of the urology service department of surgery at Memorial Sloan Kettering Cancer Center, New York City, New York

“Although [whole-gland] treatments are very successful, from the oncologic perspective, our goal was to develop and test a new treatment modality in which we treat only the area with the significant cancer using focused ultrasound in the MRI gantry,” says Behfar Ehdaie, MD, MPH.

Study finds focal therapy a safe option for treating intermediate-risk prostate cancer

In this video, Kelly L. Stratton, MD, discusses further research on the study, “Novel weekly immunotherapy dosing with avelumab tolerated during Bacillus Calmette-Guerin induction therapy: Initial results of the ABD trial,” 

presented at the 2021 American Urological Association Annual Meeting

, and his take on the current state of BCG-unresponsive non–muscle-invasive bladder cancer. Stratton is an assistant professor of urologic oncology at the University of Oklahoma, Oklahoma City.

“BCG-unresponsive non–muscle-invasive bladder cancer is really [an] evolving space with a lot of uncertainty,” says Kelly L. Stratton, MD.

Dr. Stratton discusses combo of avelumab and BCG in NMIBC

In patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), one of the main concerns is preserving their ejaculatory and erectile function post-treatment. In recent years, many researchers are innovating new treatments and therapies that prioritize that preservation.

In a study presented at the 2021 American Urological Association Annual Meeting,

 Bilal Chughtai, MD, and his team of investigators implemented the new iTind system, designed to treat patients with LUTS secondary to BPH by implanting the device via a cystoscopic procedure. Chughtai is an associate professor of urology, obstetrics and gynecology at Weill Cornell Medicine and an attending urologist at New York-Presbyterian Hospital, New York City, New York.

Please provide an overview of the iTind system and its use in treating LUTS secondary to BPH.

The iTind system is a novel system that is FDA-approved for treating enlarged prostate. Essentially, the way the iTind system works is that there is a device that is placed within the prosthetic urethra and incises the prosthetic urethra at the 12, 5 and 7 o'clock positions. These incising struts reshape the urethra over the course of 5 to 7 days, and then the whole device is removed. What's novel about the iTind system is that it's one of the first treatments that can be deployed through a flexible cystoscope, as well as the fact that there is no heat energy used or permanent foreign body that's left within the prosthetic urethra.

What are the advantages of iTind compared with other treatments for BPH?

When it comes to iTind, the biggest advantages are that it can be done completely in the office and through a flexible cystoscope with local anesthetic. Also, it doesn't have a permanent foreign body. The iTind device is removed after approximately 5 to 7 days, and there's no energy that's delivered to the prosatic tissue. Therefore, that translates to improvement in lower urinary tract symptoms secondary to enlarged prostate, and at the same time it doesn't change erectile function or ejaculatory function after the procedure.

What are some of the notable findings from this study, and were any of them surprising to you and your co-authors?

This was an analysis from the multicenter iTind study, and it really focused on sexual function and ejaculatory function. What we found was that there was no change across all groups in terms of sexual function or ejaculatory function. What was notable, though, was that in younger sexually active men, there is known to be an increase in erectile function post-procedure. Although this is not a statistically significant finding, it does show the fact that there's complete preservation of erectile function and ejaculatory function in this cohort.

What is the take-home message for the practicing urologist?

For the practicing urologist, I think iTind really adds to the armamentarium of procedures that are available for BPH that preserve ejaculatory and sexual function. So, it's something for urologists who are looking for office-based procedures to incorporate that can help their practice.

Is further research on this topic planned? If so, what will the focus be?

My understanding is that the company does have further trials that they're looking at. At this point, we are offering iTindat my practice and are collecting data to see what the results look like longer term and generate real-world evidence for it.

Is there anything else you feel our audience should know about this research?

Ultimately, the iTind system is novel and new. I think the data is out to about 3 years now, so the data is a little bit on the immature side, but it's very promising. I think the fact that this is one of the first treatments that doesn't leave a permanent foreign body, and the fact that there's no energy delivered shows a lot of promise and has a lot of interest from the patient standpoint.

1. Chughtai B, Kaminetsky J, Shore N. Preservation of ejaculatory and erectile function with iTind system for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Paper presented at 2021 American Urological Association Annual Meeting. September 10-13, 2021; virtual. Abstract MP01-06

In a study presented at the 2021 AUA annual meeting, Bilal Chughtai, MD, and co-authors implemented the new iTind system, designed to treat patients with LUTS secondary to BPH by implanting the device via a cystoscopic procedure.

iTind preserves ejaculatory and erectile function in patients with BPH

 discusses the takeaways associated with the findings from the study, “Vibegron for the treatment of patients with dry overactive bladder: A subgroup analysis from the EMPOWUR trial,” presented at the 2021 American Urological Association annual meeting. Staskin is a director of the Center for Male and Female Pelvic Health and associate professor of urology at Tufts University, Boston, Massachusetts.

“Patients want to see an improvement. They want a drug that obviously is efficacious and safe, where the side effects are low,” says David Staskin, MD.

Dr. Staskin discusses counseling patients on vibegron for OAB

Dr. Dowling is president of Dowling Medical Director Services, a private health care consulting firm specializing in quality improvement, clinical informatics, and health care policy affecting specialty care. He is the former medical director of a large, 

Most of the demographic information about urologists in the United States today comes from the American Urological Association (AUA), an organization with 7415 active members.

 The self-reported information has been used to support concerns about urology manpower needs, the aging urology workforce, and other policy matters of interest to the specialty. The publicly available information cannot reliably describe other details of the contemporary urology practice: level of activity, who practices in a group setting, how large the group is, the number of specialties practicing in the same organization, etc. In this article, I will summarize data from another source of information that can begin to answer some of these questions and what it might mean for your practice.

The Centers for Medicare & Medicaid Services (CMS) maintains several data sets of clinicians who participate in Medicare. Historically, it has been challenging to link providers to each other and to parent organizations in the National Provider Identifier (NPI) fileswhere information has been inconsistently populated. CMS is now publishing a robust downloadable file associated with the Quality Payment Program (QPP).

 Updated every few weeks, this file is an alternative source of information about urology practice and may better reflect real-world practice circumstances because most of the included clinicians have participated in the QPP. CMS needs to identify relationships between organizations (essentially tax ID numbers) and clinicians (NPI numbers) to properly calculate scores and fee schedule adjustments. Those relationships can be derived from the downloadable file and inform us about urology practice. The data cannot tell us about supergroups (groups of groups), networks, or subgroups.

The CMS data include 9324 unique clinicians identified as urologists in 1921 unique organizations (1268 urologists are associated with more than 1 organization). A total 6672 of these clinicians in 1609 organizations received a final Merit-based Incentive Payment System score in 2019 (ie, were actively seeing Medicare patients). The file does not include age or birth year but does include the year of graduation from medical school—a rough proxy for age. Over two-thirds of the urologists in this Medicare data set graduated from medical school after 1990; 11% are women, and 89% are men. Fifty percent of urologists in this database practice in just 10 states (some urologists are associated with more than 1 state), and the average distribution of all urologists based on 2019 population estimates is 1 urologist per 34,323 people.

A total of 3285 urologists are associated with 408 organizations where urology is the dominant specialty (there are more urologists in the organization than any other single specialty). In 373 (91%) of these groups, urologists constitute at least 50% of the clinicians. The number of urologists in these 408 groups ranges from 1 to 118 (mean, 8.4; median, 4); only 43 groups have 20 or more urologists. The most common other specialties represented in the groups where urologists are the dominant specialty are physician assistants, nurse practitioners, radiation oncologists, and pathologists. A total of 210 organizations have advanced practice partners (APPs; mean, 5 clinicians), 67 organizations have radiation oncologists (mean, 3.5), and 99 organizations have pathologists (mean, 1.7); 35 urology-dominant organizations have all 3 specialties. The size of these groups ranges from 2 to 281 clinicians (mean, 13; median, 5.5).

More than 5500 urologists are associated with organizations where urology is not the dominant specialty. These include very large organizations, such as health systems and universities, and much smaller organizations. The most common dominant specialties in these groups are primary care, APPs, and general surgery (

). The size of these groups ranges from 43 to 7478 clinicians (mean, 486; median, 255); the urologists’ number ranges from 1 to 104 (mean, 6.5; median, 4).

Finally, the data include all unique practice locations for an individual clinician. The number of unique locations associated with 9234 unique urologists ranges from 1 to 55 (mean, 2.4; median, 2). Those urologists associated with urology-dominant groups have fewer unique locations per clinician (range, 1-12; mean, 2.0; median, 1) than those urologists associated with organizations where urology is not dominant (range, 1-55; mean, 2.5; median 1). Twenty-one percent of urologists in urology-dominant practices were associated with more than 3 addresses vs 29% of urologists in the other practices.

This analysis comes with caveats. First, the information may not be generalizable to the entire specialty, as some providers may not participate in Medicare. Second, many individual clinicians are associated with more than 1 organization—it isn’t possible to know which of the associations are primary in these cases. Similarly, it isn’t possible to know which of the associated practice addresses are active or inactive. It isn’t possible to reliably identify solo practices in these data—some urologists practicing by themselves may be part of a common billing organization. Finally, most of the information in this file is self-reported, such as year of graduation from medical school and name of medical school, and some clinicians have incomplete data. It is not possible to verify the accuracy of self-reported data.

What does this mean for your practice and your patients? The CMS downloadable file provides interesting food for thought. Physicians may be best positioned to control the clinical and business aspects of their practice if they are the dominant group in the parent organization. The Medicare data suggest that about 35% of urologists are in organizations they dominate (what might have once been called single-specialty groups). This compares favorably with general surgery (17%), cardiology (28%), and orthopedic surgery (31%). Many providers are probably familiar with factors that have caused specialists to consolidate, and these data help quantify that consolidation—at least among Medicare providers. Urology-dominated groups appear to have a foothold, which is good news for those who prefer this model of practice. Others might argue that a multispecialty model offers the potential for better care coordination and value-based care. These data do not help answer that question but suggest that a majority of urologists practice in organizations where they are not the dominant specialist—at least among Medicare providers. One size does not fit all [urologists] today, but the demands of patients and payers are likely to shape the landscape of tomorrow.

1. AUA member profile. American Urological Association Inc. Updated April 2021. Accessed August 3, 2021. https://www.auanet.org/documents/about/Member-Profile%280%29.pdf

2. Doctors and clinicians: national downloadable file. Centers for Medicare & Medicaid Services. Updated June 4, 2021. Accessed August 3, 2021. https://data.cms.gov/provider-data/search?theme=Doctors%20and%20clinicians

3. State population by rank. Infoplease. Accessed August 3, 2021. https://www.infoplease.com/us/states/state-population-by-rank

More than a third of urologists work in a urology-dominant practice

What CMS data reveal about urology practice composition

Combining the immunotherapy avelumab (Bavencio) with standard neoadjuvant chemotherapy induced pathological complete responses (pCRs) in over half of patients with nonmetastatic muscle-invasive bladder cancer (MIBC), according to findings from the phase 2 AURA trial presented during the 2021 ESMO Congress.

Patients were randomized to avelumab (A) plus cisplatin-gemcitabine (CG + A) or dose-dense MVAC (DD-MVAC) plus A. The MVAC regimen comprises methotrexate (M), vinblastine (V), Adriamycin (A), and cisplatin (C). Across all patients in the study, 57% achieved a pCR and 61% of patients were downstaged to <ypT2N0.

The pCR rate was 54% in the CG + A arm, with 57% of patients downstaged to <ypT2N0. Among patients receiving DD-MVAC + A, the pCR rate was 61%, with 64% of patients downstaged to <ypT2N0.

“This phase 2 trial is the first evidence of avelumab in the neoadjuvant bladder cancer setting showing high pCRs when used in combination with standard chemotherapy. These combinations were safe and did not compromise surgical resection,” said lead study author Nieves Martinez Chanza, MD, PhD, a medical oncologist in the Oncology Medicine Department at Jules Bordet Cancer Institute, Brussels, Belgium.

The prospective, multicenter, noncomparative randomized phase 2 AURA trial enrolled patients with cT2-4aN0-2M0 MIBC who were scheduled to receive radical cystectomy and lymphadenectomy. The data shared during ESMO were for 56 patients, 28 of whom were randomized to CG + A and 28 of whom were randomized to DD-MVAC + A.

In the CG + A arm, the median age was 69 years (range, 41-81) and 64% were male. Twenty-five patients had pure urothelial carcinoma and 3 patients had mixed histology, defined as squamous differentiation with a predominant urothelial component (>50%). Regarding clinical stage at baseline, 18 patients were T2N0, 5 were TxN

 (evidence of lymph-node involvement), 3 were T3N0, and 2 were T4N0.

Among patients receiving DD-MVAC + A, the median age was 62 years (range, 51-77) and 79% were male. Twenty-two patients had pure urothelial carcinoma and 6 patients had mixed histology. Regarding clinical stage at baseline, 17 patients were T2N0, 7 were T3N0, 3 were TxN

There were 6 patients who did not undergo cystectomy; however, they were included in the intention to treat analysis. The primary end point of the study was pCR, with the goal of reaching a pCR (ypT0/isN0) rate >25% in each arm. Secondary end points for the trial were pathologic downstaging rate (<ypT2N0) and safety.

The median number of avelumab cycles received was 4.4 (range, 1-7) overall, comprising a median of 5.11 (range, 1-7) in the CG + A arm and 3.8 (range, 1-4) in the DD-MVAC arm.

Regarding safety, the most frequently reported grade 3/4 adverse events (AEs) were thrombocytopenia (25% in the CG arm vs 11% in the DD-MVAC arm), neutropenia (18% vs 4%, respectively), febrile neutropenia (4% in each arm), and creatinine increase (14% in each arm).

“Toxicity related to avelumab was relatively rare, with only one grade 3 AE (immune-related thrombocytopenia) and no patients requiring systemic steroids,” said Chanza, adding, “Importantly, no patients failed to undergo surgery due to an AE.” There also were no treatment-related deaths.

Looking ahead, Chanza said the investigators are anticipating results from a separate cohort of the AURA study that is examining avelumab-based neoadjuvant chemotherapy in cisplatin ineligible patients. These patients are being randomized to avelumab either alone or combined with gemcitabine and paclitaxel.

“Translational research and a survival analysis are also ongoing,” Chanza said in her concluding remarks.

1. Chanza NM, Carnot A, Barthelemy P, et al. Avelumab (A) as the basis of neoadjuvant chemotherapy (NAC) regimen in platinum eligible and ineligible patients (pts) with non-metastatic muscle invasive bladder cancer (NM-MIBC). 2021 ESMO Congress. September 16-21, 2021. Abstract 659MO.

Combining avelumab with standard neoadjuvant chemotherapy induced pathological complete responses in over half of patients with nonmetastatic muscle-invasive bladder cancer.

Avelumab-based neoadjuvant therapy shows potential in nonmetastatic MIBC

The FDA has authorized the marketing of Paige Prostate, an AI-based software platform to help pathologists identify prostate cancer when they review slide images from prostate biopsies.

The standard biopsy review process involves the pathologist examining digitally scanned slide images from prostate biopsies to find areas that are suspicious for cancer. Paige Prostate provides a supplementary assessment of the image and locates the area with the highest probability of harboring cancer. The pathologist can then examine this specific area further if they did not identify it on their initial assessment.

“Pathologists examine biopsies of tissue suspected for diseases, such as prostate cancer, every day. Identifying areas of concern on the biopsy image can help pathologists make a diagnosis that informs the appropriate treatment,” 

Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health

, stated in a press release. “The authorization of this AI-based software can help increase the number of identified prostate biopsy samples with cancerous tissue, which can ultimately save lives.”

In making its decision to authorize the marketing of Paige Prostate, the FDA reviewed the results of a clinical study involving 16 pathologists who assessed 527 slide images of prostate biopsies. The images had been digitized with a scanner and included 171 with cancerous tissue and 356 with benign tissue. All pathologists performed 2 assessments of each slide image, one with the assistance of Paige Prostate and one without.

The results showed that detection of cancer on individual slide images was improved by an average of 7.3% with the assistance of Paige Prostate versus the pathologists’ unassisted reads. There was no impact on the assessment of the benign slide images. Of note, the impact of Paige Prostate on final patient diagnosis was not an end point of the study, as that is typically determined following multiple biopsies.

The FDA noted that false negative and false positive results are potential risks with Paige Prostate. However, the agency maintained that these risks are mitigated by the fact that the device is only a supplementary tool used to assist pathologists who are able to provide their own independent evaluation that accounts for a broad spectrum of relevant clinical information. The risks of false negatives/positives are also mitigated by the pathologists’ capacity to conduct additional laboratory studies on the biopsy samples before making a final diagnosis.

Paige Prostate, which is marketed by Paige.AI, was reviewed by the FDA through its De Novo premarket review pathway, which is specifically for novel devices that are considered by agency to be low- to moderate-risk.

1. FDA Authorizes Software that Can Help Identify Prostate Cancer. Published online September 21, 2022. Accessed September 21, 2022. https://bit.ly/3lKAEGb.

Paige Prostate AI-based software provides pathologists with a supplementary assessment of prostate biopsy images that identifies the area with the highest likelihood of harboring cancer.

What CMS data reveal about urology practice composition

Avelumab-based neoadjuvant therapy shows potential in nonmetastatic MIBC

FDA authorizes AI-based software for prostate cancer detection