Kerr is group content director for Urology Times.

Richard R. Kerr

The 2020 AUA annual meeting has been canceled as a result of the coronavirus (COVID-19) pandemic.

“Due to rapidly escalating health concerns, coupled with U.S. President Trump’s emergency declaration, the AUA has made the difficult, but necessary decision to cancel the 2020 AUA Annual Meeting in Washington, DC. There is no higher priority to the AUA than the health, safety and well-being of our members, staff, partners, volunteers, guests and the community at large,” the AUA said in a statement.

“We recognize the AUA Annual Meeting is a major global event for the urology community and preparing for it involves the time and talent of a great many of our physician volunteers, speakers and exhibitors. We are incredibly grateful for their time and deeply disappointed not to be able to hold the meeting as planned.”
	The association said it was unable to reschedule the meeting, “given the logistics that go into organizing a meeting of this size.” It added, however, that “in the coming weeks we intend to tap into the innovative spirit of our specialty and share the abstracts, surgical videos and other important clinical education from our meeting as we are able.”
	Separately, the AUA’s third Annual Urology Advocacy Summit, originally scheduled for mid-March on Capitol Hill, has been postponed until later this year, and the April meeting of the American Association of Genitourinary Surgeons has been canceled. Earlier, the European Association of Urology announced it postponed its annual congress from March 20-24 to July, and year’s Urological Society of Australia and New Zealand annual scientific meeting was canceled outright.

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AUA 2020 annual meeting canceled

Byron H. Lee, MD, PhDMultiple studies on exosomes, data from the IMvigor 210 trial of atezolizumab (TECENTRIQ), and research on prehabilitation for cystectomy were among the highlights in bladder cancer from the 2016 AUA annual meeting. The take-home messages for bladder cancer were presented by Byron H. Lee, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York.   

Exosomes, which are membrane-enclosed, 30- to 100-nanometer vesicles found in bodily fluids, can modulate the immune system, alter target cell behavior, promote angiogenesis, and facilitate migration of cancer cells. Four studies found: Exosomes from invasive and noninvasive bladder cancer cell lines have distinct microRNA signatures and can be taken up by naïve fibroblasts. A 38-gene panel from urinary exosomes may be used to develop a new assay for urothelial carcinoma detection. Increased levels of tumor-associated mRNA and long non-coding RNA such as HOTAIR were found in exosomes isolated from patients with invasive bladder cancer. Bladder cancer cell lines shed exosomes at much higher quantities than non-transformed urothelial cell lines and have distinct mRNA expression profiles.

Atezolizumab (TECENTRIQ), an anti-PD-L1 antibody indicated for patients with platinum-treated locally advanced or metastatic urothelial carcinoma, showed significantly improved objective response rate versus historical controls in the IMvigor 210 trial. There was a 27% response rate in high expressers of PD-L1 and a 15% objective response rate in all comers. Responses were durable, poor prognostic factors did not preclude response, and the drug was well tolerated. 

Androgen receptor activation may play a role in bladder carcinogenesis and potentially serve as a therapeutic target. Analysis of gene expression data found that expression of 5-alpha-reductase isozyme subtype and genes involved in androgen signaling are associated with bladder cancer cluster type. Also, anti-androgens can inhibit colony formation in vitro and growth in a xenograft model of a carcinogen-transformed, androgen receptor-expressing urothelial cell line.

In one new model of bladder cancer, a tet-inducible UPII-CRE was used to delete P53 and/or PTEN in mice; knockout of both genes led to development of invasive tumors with squamous differentiation and expression of high levels of basal cell markers. In a second, study authors successfully cultured organoids derived from surgical specimens with similar mutation profiles as the parental tissue.

Prehabilitation for cystectomy was feasible and safe in two presentations. Both groups used a 2- to 3-week program, reported good patient compliance (75%-80%), and demonstrated measurable improvement in postoperative fitness and endurance.

		Robotic cystectomy utilization has increased over time to 20% to 30%. Perioperative and short-term outcomes (length of stay, complications, and readmission rates) are similar to open cystectomy. No significant differences in long-term oncologic outcomes were seen between robotic and open cystectomy, but studies are needed to compare late postoperative complications such as ureterointestinal and urethrointestinal anastomotic strictures, and renal function deterioration.

		A study on the potential of tumor dissemination under pneumoperitoneum, which examined mRNA expression and epithelial cell markers from intravesical and pelvic washes in patients undergoing robotic cystectomy, found intravesical washes were positive for bladder cancer markers but pelvic irrigations were typically not positive for these markers. However, epithelial markers were detected in the pelvis in one patient with node-positive disease.

		A subset of patients with metastatic bladder cancer who undergo surgery will achieve long-term cancer control, but it’s still unclear whether this is due to patient selection. Further studies are warranted to identify who would benefit from surgery.

		An oncolytic adenovirus, CG0070, was studied in nonmuscle-invasive bladder cancer. In 22 patients who were given this drug or standard intravesical therapy, 53% of those receiving the adenovirus had initial complete response and six had a durable complete response at 6 and 9 months, comparable to the 57% initial complete response in the control patients. Toxicities were similar between the two groups.

		OGX-427, a second-generation antisense oligonucleotide, was administered intravesically prior to surgery in 23 patients with nonmuscle-invasive and bladder cancer one with muscle-invasive disease that was treated by transuretheral resection and radical cystectomy. OGX-427 decreased Hsp27 expression in the tumors when compared with pre-treatment. Eight patients had initial complete responses.

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Multiple studies on exosomes, data from the IMvigor 210 trial of atezolizumab (TECENTRIQ), and research on prehabilitation for cystectomy were among the highlights in bladder cancer from the 2016 AUA annual meeting.

Bladder Cancer: Androgen receptor activation a potential therapeutic target

It’s been said that the best treatment for low-risk prostate cancer is no treatment at all. A number of studies at the 2015 AUA annual meeting appeared to bear that out, showing active surveillance to be a safe and increasingly common approach in this patient population.

	The meeting’s “Crossfire: Controversies in Urology” was a highlight for the second year in a row, with debates about whether shock wave lithotripsy should be retired and whether focal therapy for prostate cancer is hope or hype drawing big crowds.  

	Abstracts comparing surgical techniques, including robotic techniques, were hot, as were studies on new treatments for BPH, the use of mesh in pelvic organ prolapse, and the safety of testosterone replacement therapy.

“Best of AUA 2015” report provides a guide to the meeting’s take-home messages in 15 therapeutic areas-an information-packed, condensed summary of the top papers and presentations. The editors’ choices for high-interest messages are highlighted in boldface type.

Minimally Invasive Surgery (Laparoscopy/Robotics)

		A retrospective review of 223 patients managed with AS found that obese men were twice as likely to have disease progression on biopsy than non-obese men. There was a trend toward high-grade cancer in men in whom AS failed despite no difference in body mass index on the initial diagnostic biopsy.

		In a prospective study, obesity was significantly associated with high-grade and metastatic disease in men with clinically localized prostate cancer.

		Current metformin use was associated with a significantly decreased risk of prostate cancer in a nested case-control study.

In a meta-analysis of 18 studies, testosterone replacement therapy for symptomatic hypogonadism did not increase levels of PSA nor the risk of prostate cancer development.

		Metformin use was associated with a significant survival advantage among diabetic veterans with prostate cancer.

		Magnetic resonance fusion targeted biopsy detected more Gleason grade ≥7 cancer than 12-core systematic biopsy, missing 4% of men with mSS ≥4 lesions while systematic biopsy missed 15%.

		Magnetic resonance fusion targeted biopsy reduces the detection of indolent disease while significantly improving the detection and risk stratification of high-grade prostate cancer.

		Positive [11c] choline positron emission tomography/computed tomography after biochemical failure predicts prostate cancer survival in hormone-naïve prostate cancer patients.

		Combining urine PCA3 and TMPRSS2:ERG tests can enhance detection of high-grade prostate cancer. When sensitivity was set to 95%, the specificity improved to 39%, avoiding 49% of unnecessary biopsies. In a validation cohort, specificity was improved to 33% while retaining high sensitivity (93%).

		Combined risk scoring based on epigenetic profiling of GSTP1, APS, RASSF1, and histopathology is strongly correlated with the detection of aggressive prostate cancer upon repeat biopsy.

		The 17-gene Genomic Prostate Score (GPS) assay may improve risk stratification for men with newly diagnosed prostate cancer who are candidates for active surveillance.

		For prostate cancer patients considering deferred treatment, the combined clinical cell cycle risk score provides significant prognostic information at disease diagnosis.

		The 4Kscore maintains good discrimination for risk of high-grade prostate cancer in a subpopulation of men with PSA ≤4.0 ng/mL, with a sensitivity of 95% and a specificity of 56%.

		Homogeneous PTEN loss is associated with decreased time to biochemical recurrence; this effect is much stronger in ERG-negative tumors than in ERG-positive tumors.

		Hybrid PET and magnetic resonance imaging may be advantageous in men with PSA <1.0 ng/mL by increasing diagnostic certainty.

		68Ga-HBED-prostate-specific membrane antigen/PET hybrid imaging has a high sensitivity and superb specificity and accuracy for lymph node staging in intermediate- to high-risk patients with prostate cancer, and may replace current standard imaging in the future.

		Even in the context of node-positive prostate cancer, patients may have long-term survival after radical prostatectomy and extended pelvic lymph node dissection.

		In a single-institution review of 1,131 patients who qualified for active surveillance, 51% were found to have an upgraded Gleason score. Patients should be provided appropriate education and counseling about the risk associated with active surveillance.

		African-American men had similar functional outcomes after robotic prostatectomy as non-African-Americans, but African-Americans were slower to recover continence and less likely to achieve “trifecta” status.

		Metabolic syndrome is associated with an increased risk of extraprostatic and high-grade disease on final RP pathology, and an increased need for salvage therapy. However, with more aggressive resection, similar failure-free outcomes can be achieved in well-selected patients.

		Intermittent androgen deprivation (ADT) may be a valid option for select patients with locally advanced prostate cancer or relapsing M0 prostate cancer.

		Results from the SEARCH database show an overall survival benefit for men with biochemical recurrence after radical prostatectomy if ADT is initiated before PSA reaches 10.0 ng/mL. This benefit is stronger when ADT is initiated before PSA reaches 5.0 ng/mL. The survival benefit of ADT, however, must be weighed against long-term side effects.

		Sipuleucel-T (Provenge) plus ADT show durable PSA responses, regardless of their sequence, in men with biochemical recurrence of prostate cancer at high risk of developing metastases.

	Presented by Sunil Sudarshan, MD, University of Alabama, Birmingham

		Detrusor overactivity induced by cerebral infarction is associated with enhanced activity of Rho-kinase.

		Urge incontinence in women is associated with subcortical changes, including atrophy of the hippocampus.

		Enhanced spinal glycinergic signaling reduces detrusor overactivity in rats with spinal cord injury.

		A drosophila model of xanthinuria demonstrated a role for heterogeneous nucleation in non-calcium urinary stones.

 colonization normalized oxalate excretion in a rat hyperoxaluria model.

		siRNA knock down of glyoxylate oxidase reduced urinary oxalate excretion in a mouse model of primary hyperoxaluria Type I, representing a potential new target.

		Inhibition of pericyte function with an anti-platelet-derived growth factor receptor beta-blocking antibody induced deterioration of erectile function in normal mice.

		Alpha-adrenergic modulation improved erectile function after bilateral crush cavernosal nerve injury in rats.

		A vascular leakage blocker (SAC-1004) restored erectile function in a chemically induced mouse diabetes model.

		Gene expression profiling suggests distinct molecular subtypes of BPH driven by differences in androgen gene regulation.

		BPH expresses higher levels of ligand-independent Arv7 than normal prostate, which has implications for treatment with 5-alpha-reductase inhibitors.

		Whole exome sequencing identified NPAS2 mutations in a family with nonobstructive azoospermia.

		A subset of infertile patients carries the G75C polymorphism in PGAM4, an X-linked retrogene.

		Antioxidant supplementation during cryopreservation improves post-thawing sperm parameters.

Urology Times’ “Best of AUA 2015” report provides a guide to the meeting’s take-home messages in 15 therapeutic areas-an information-packed, condensed summary of the top papers and presentations.

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	In the search for new ways to combat urinary tract infections, researchers have shown that an experimental drug that stabilizes a protein called HIF-1alpha protects human bladder cells and mice against a major UTI pathogen.

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	The drug may eventually provide a therapeutic alternative or complement to standard antibiotic treatment, say study authors from the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences.

	HIF-1alpha is known to influence the innate immune response, researchers say. Like many regulator proteins, HIF-1alpha is relatively short-lived. To increase HIF-1alpha levels, researchers have developed drugs that delay its breakdown. This same pathway has been the target for drugs now in advanced clinical trials for treatment of anemia.

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	In the current study, lead author Victor Nizet, MD, and colleagues explored the use of HIF-1alpha-stabilizing drugs to boost the innate immune response to uropathogenic 

 (UPEC) bacteria, a major cause of UTIs. In healthy human urinary tract cells, treatment with the drugs increased HIF-1alpha levels. Such cells were then more resistant to UPEC attachment, invasion, and killing than human urinary tract cells with normal HIF-1alpha levels, Dr. Nizet’s team said in a University of California, San Diego 

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	Using a mouse model of UTI, the researchers showed that administration of HIF-1alpha stabilizers directly into the bladder protected against UPEC infection. They also found that invasion of bladder cells, a critical early step in the infection process, was reduced in treated mice compared to untreated mice.

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	To verify the importance of HIF-1alpha in the defense against UPEC infection, the researchers studied mice with reduced HIF-1alpha levels. Exposed to UPEC, these mice were more susceptible to bladder infection, and pre-treatment with HIF-1alpha stabilizers made no difference. This demonstrates that the drugs combat UTIs through their effect on HIF-1alpha.

	Finally, the researchers examined whether treatment with HIF-1alpha stabilizers would be beneficial against an established UTI. To do this, they infected mice with UPEC first and then administered the drugs into the bladder 6 hours later. The treated mice had a more than tenfold reduction in bladder colonization with the bacteria, demonstrating that HIF-1alpha stabilization is beneficial even after the initial infection.

	“The ultimate goal of this research will be to advance HIF-1alpha stabilizers toward clinical trials in humans, using versions of the drug that can be taken orally and reach the urinary tract,” Dr. Nizet said.

	One study co-author is an employee of Aerpio Therapeutics.

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An experimental drug that stabilizes a protein protects human bladder cells against a major UTI pathogen, researchers say.

Richard R. Kerr

Articles

AUA 2020 annual meeting canceled

Bladder Cancer: Androgen receptor activation a potential therapeutic target

Best of AUA 2015: PCa surveillance, surgical controversies create buzz

Novel agent may protect against major UTI pathogen