Don Schrader

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.

Articles

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.

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

Click here for more Best of AUA 2014 coverage

• A review of American Board of Urology case logs for 2003 to 2012 showed that 54.2% of 441,162 procedures for upper tract urinary calculi were managed ureteroscopically, 41.3% by extracorporeal shock wave lithotripsy (SWL), and 4.5% by PCNL.

	• Erythropoietin increased recovery of ureteral peristalsis in a murine model of obstructive uropathy.

	• Human macrophages facilitate kidney stone clearance.

	• Balance between the activation of inflammatory macrophages and suppression of anti-inflammatory macrophages may play an important role in kidney stone formation, and these markers may have potential as biomarkers to reflect urinary stone risk.

	• Reusable laser fibers cleaved with various tools showed significant variability in power output and light dispersion.

	• Various studies of ball-tipped lasers found degradation at high-energy settings, comminution efficiency similar to standard fiber, less ureteroscope damage, and potential cost savings.

	• At 16-month median follow-up, a study of 230 metallic stents in 86 patients with chronic ureteral obstruction showed 24% failure rate and average lifespan of 7.4 months but greater durability compared with polymer stents.

	• Analysis of analgesic use, complications, and stone-free rates following upper-pole percutaneous nephrolithotomy (PCNL) showed no differences between upper- and lower-pole access with respect to overall complications or analgesic requirements but superior stone-free rate for upper-pole procedures.

	• A study of 50 cases of outpatient PCNL showed no major complications or deaths, leading to the conclusion that the procedure is safe in highly selected patients.

	• Imaging evaluation 4 to 6 weeks after stent removal showed hydronephrosis rates of 2.4% after ureteroscopy and 5.7% after PCNL but with spontaneous resolution in most cases.

	• A randomized trial of initial ultrasound versus computed tomography imaging for suspected nephrolithiasis in 2,759 patients at 15 emergency departments showed no difference in serious adverse events, pain at 3 or 7 days, return to emergency department, or hospitalization at 3, 7, or 180 days according to whether patients had ultrasound evaluation by an emergency physician or radiologist or had abdominal CT as initial study.

	• A study of the comparative effectiveness of shock wave lithotripsy and ureteroscopy showed a retreatment rate of 11% with SWL and <1% for ureteroscopy in almost 48,000 procedures.

	• A comparison of cost-effectiveness of ureteroscopic laser lithotripsy versus shock wave lithotripsy for renal calculi showed single-procedure stone-free rates of 95% for URS and 55% for SWL (

	• A study of the economic impact of ureteroscope repairs showed 20 device repairs cost $115,000, which contributed to a negative net margin (–$455/case) for 11 inpatient procedures, whereas a positive margin was maintained for outpatient procedures ($659/case), resulting in a net positive margin of $594/case.

	• A 2-day preoperative course of antibiotics before PCNL is as effective as a 7-day course, but there was no overall consensus on extended-course antibiotics aside from reserving treatment for carefully selected patients.

	• Non-obese patients treated with potassium citrate (Urocit-K) are more likely to develop brushite stones, whereas no obese patient developed a brushite stone after treatment with potassium citrate.

	• Bisphosphonate treatment not only improved bone mineral density but also reduced urolithiasis recurrence in Japanese men with osteoporosis.

	• A phase II, placebo-controlled trial of a multi-herbal therapy for stone disease was associated with a significantly higher expulsion rate (

<.03), significantly smaller stone size (

<.001), although the mechanism of action remains unknown.

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Matthew D. Dunn, MD, presents the take home messages on stone disease/endourology from the AUA annual meeting in Orlando, FL.

Author | Don Schrader

Articles

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

Best of AUA 2014: Stone Disease/Endourology