“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature. Dr. Mian is professor of surgery in the division of urology at Albany Medical College, Albany, NY.

Depending on tumor characteristics and length of follow-up, recurrent nonmuscle-invasive bladder cancer (NMIBC) can develop in 20% to 40% of patients following initial intravesical Bacillus Calmette-GuÃ©rin therapy. Most experts recommend radical cystectomy for patients with BCG-unresponsive NMIBC. Yet, many patients are either not good candidates for major surgery or they desire to preserve a functioning bladder. Many bladder preservation strategies, including various immunotherapy and chemotherapy agents, in various combinations and schedules, have been tested over the years but most have not provided durable control of this disease.

Adopting the rationale from combination systemic chemotherapy used in advanced bladder cancer, some centers have utilized combination intravesical chemotherapy with sequential use of gemcitabine (Gemzar) and docetaxel (Taxotere) as a salvage strategy for patients with recurrent NMIBC. To determine the effectiveness of this approach, Steinberg et al performed a retrospective analysis of the data from multiple institutions showing promising results in this difficult cohort of patients 

The authors pooled the data from 11 different centers and identified 276 patients with recurrent NMIBC (median age, 73 years) treated with sequential gemcitabine and docetaxel from 2009 to 2018. The patients had undergone a median of two previous intravesical induction courses and a median of one BCG induction course (range, 1-4). Of these, 38% were classified as BCG unresponsive, ie, early recurrence (within 6-12 months) of various NMIBC pathology.

The instillation protocol included gemcitabine, 1 gram in 50 mL saline or water instilled via Foley catheter and allowed to remain in the bladder for 60 to 90 minutes. After drainage of the gemcitabine, docetaxel, 37.5 mg in 50 mL saline, was instilled. The catheter was removed and patients were instructed to not void for 60 to 120 minutes. This induction regimen was administered once per week for 6 weeks.

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Most institutions used this combination intravesical chemotherapy once per month for 24 months. Side effects were reported by 41% of patients, requiring modification of schedule in 10%. The most frequently noted side effects included irritative urinary symptoms (22%), dysuria (16%), and hematuria (11%).

The data were presented separately for any recurrence or high-grade recurrence after treatment. Any recurrence-free survival (RFS) in all treated patients was 60% at 1 year and 46% at 2 years, with a median follow-up of 13.9 months. Median time to recurrence was 6.8 months (range, 2.0 to 67.3). RFS for patients with any carcinoma in situ was 60% at 1 year and 43% at 2 years, and RFS for those with papillary disease alone was 62% at 1 year and 51% at 2 years.

High-grade RFS in all patients was 65% at 1 year and 52% at 2 years. In the BCG-unresponsive group, 50% of those with carcinoma in situ and 58% of those with papillary disease were free of high-grade recurrence at 2 years. Using the maintenance protocol was associated with lower recurrence rate, both low grade and high grade 

<.01). Of the 43 patients undergoing cystectomy (at median of 11.3 months), 38 were due to recurrent disease. Final pathology showed stage T0 in seven patients and T2 or higher in 11 patients, four of whom had lymph node metastases.

Forty-four patients (16%) died at median follow-up of 22.9 months, and 13 (5%) died of metastatic bladder cancer. In patients dying of bladder cancer, carcinoma in situ was the initial diagnosis in eight of 13 patients. The bladder cancer-specific mortality rate was 1% at 1 year and 4% at 2 years, while the all-cause mortality rate was 3% and 13%, respectively.

This report on sequential intravesical gemcitabine and docetaxel for BCG-recurrent NMIBC shows promising results. The recurrence-free rates appear to be better than many previously reported attempts at controlling recurrent or resistant disease. This may be due in part to the fact that these patients were treated early in the salvage paradigm (history of one or two inductions) and not heavily pre-treated with multiple induction or maintenance courses. This regimen appears to be well tolerated and with an acceptable rate of schedule modification. Because there was no standardized method for collecting the data, the rate and severity of adverse effects are likely underreported.

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In this era of BCG shortage, we may be forced to develop new standards and alternative strategies for bladder preservation. Can the sequential intravesical chemotherapy replace BCG in patients with newly diagnosed NMIBC with sufficient efficacy? Or can it replace maintenance BCG so that the precious supply of available BCG can be reserved for patients with initial high-risk NMIBC?

Radical cystectomy is probably the most complex urologic surgery, with a high rate of short-term complications. While it can be a life-saving intervention, it can also be life-changing event with significant implications related to quality of life and survivorship. Thus, bladder preservation will always be desired by patients. The challenges created by the BCG shortages also provide the rationale and opportunity for prospective validation of this and other bladder preservation strategies.

Articles

"In this era of BCG shortage, we may be forced to develop new standards and alternative strategies for bladder preservation," writes Badar M. Mian, MD.

Sequential gemcitabine/docetaxel promising for recurrent NMIBC

Pharmacotherapy for reducing risk of stone recurrence is best reserved for patients with more aggressive disease who are at higher risk for another stone-related event, said Brett A. Johnson, MD, at the 2019 World Congress of Endourology and SWL in Abu Dhabi.

His statement was based on the findings of a retrospective study that compared the risk of stone recurrence between patients managed with pharmacotherapy versus conservative therapy while controlling for disease severity.

“Pharmacotherapy for stone prevention in stone formers has proven effective, but compliance remains poor, primarily due to side effects. Our study aimed to determine if better patient risk stratification may help delineate what patients are most likely to benefit from pharmacotherapy,” said Dr. Johnson, assistant professor of urology, UT Southwestern Medical Center, Dallas.

“Our analyses showed a benefit of pharmacotherapy for delaying stone-related events in patients with a strong history of stones, but indicate that conservative therapy is likely to be as effective in lower risk patients.”

The study pooled data from four academic centers that are participants in the Multicenter collaboration to Study Treatment Outcomes in Nephrolithiasis Evaluation (MSTONE). The centers include UT Southwestern, the University of Wisconsin, Madison, Vanderbilt University, Nashville, TN, and the University of Iowa, Iowa City.

It included 245 patients seen in the clinic for a stone event between July 2001 and April 2015, were managed with pharmacotherapy or conservative therapy comprised of fluid intake and dietary recommendations, and had a minimum follow-up of 1 year. Patients who started on conservative therapy and were switched to medical therapy were included in the pharmacotherapy group.

The patients were stratified into three risk groups according to the number of previous spontaneously passed stones: low risk, 0; moderate risk, ≤10; high risk, >10. The population included 62 low-risk patients, 147 in the intermediate-risk group, and 36 high-risk patients. The percentage of patients being treated with pharmacotherapy within the three risk groups was 48%, 64%, and 78%, respectively.

“Because this was not a randomized controlled trial, we recognized that patients who are at higher risk for a subsequent stone event would be managed more aggressively. To adjust for that difference, we stratified patients into risk groups taking into account their previous stone issues,” Dr. Johnson explained.

Rate of new stone events lower in pharmacotherapy group

Median follow-up for the entire population was 29 months and similar across risk groups. Treatment groups were compared for the rate of stone events, which included new stone formation, stone growth, or an acute stone episode. In the overall population, the rate of new stone events was lower in the pharmacotherapy group than among patients managed conservatively (66% vs. 74%), but the difference was not statistically significant.

When the analysis was done for each risk group, the stone event rate was consistently lower among patients prescribed pharmacotherapy compared with those managed conservatively. Again, none of the differences between management groups achieved statistical significance for overall stone event rate.

“However, when analyzing stone event-free survival, pharmacotherapy demonstrated greater improvement for intermediate and higher risk patients. Pharmacotherapy increased the 30-month stone-free survival rate by 32% and 20% in the high-risk and intermediate-risk patients, respectively,” said Dr. Johnson.

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The Kaplan-Meier analysis of 30-month stone event-free survival rate showed a statistically significant benefit of medical therapy compared with conservative therapy for delaying a recurrent stone event in the overall population (58% vs. 46%, 

=.006) as well as in the intermediate-risk group (65% vs. 45%, 

=.005). There was a trend toward statistical significance in the high-risk group (49% vs. 17%, 

“The intermediate-risk group had the highest number of patients and therefore had greater power for detecting a statistically significant difference between management groups,” commented Dr. Johnson.

“However, the greatest magnitude difference was observed in the high-risk group.”

Dr. Johnson noted that the study did not account for treatment compliance, but that may not be an important limitation considering that patient compliance is poor with both pharmacotherapy and dietary recommendations for preventing stone recurrence. In addition, it did not stratify patients based on 24-hour urine parameters because the data were not available for all patients.

“It is not always possible to get a 24-hour urine specimen from stone patients, and so we took a very top-down view that considered what basic approach might be done in the clinic to manage patients with stone disease,” Dr. Johnson told 

“We feel our study has several strengths that include a relatively large population, a reasonably long follow-up duration, and the ability to control for disease severity.”

Pharmacotherapy reduces recurrence risk for aggressive stone disease

Single-access percutaneous nephrolithotomy (PCNL) can clear the vast majority of staghorn stones with minimal morbidity, said Tim Large, MD, at the 2019 World Congress of Endourology and SWL in Abu Dhabi.

He reported findings from a multi-institutional retrospective review showing that over a 2-year period, 301 (89%) of 340 patients with full or partial staghorn calculi were treated with single-access PCNL. Postoperative computed tomography scans identified residual stone fragments in 169 patients (56%), of which only 54 (17.9%) had a fragment >4 mm. A secondary PCNL was performed in 117 (38.9%) of the 169 patients with a residual stone.

Follow-up imaging performed at 6 weeks showed that overall, 86% of patients were rendered stone-free. Complications were rare.

“The results in our retrospective study reinforce the recommendation in both the AUA and EAU guidelines that PCNL be considered the first-line surgical intervention for patients with stones greater than 2 cm, including staghorn calculi,” said Dr. Large, assistant professor, Indiana University School of Medicine, Indianapolis.

“Alternative approaches may be chosen because of surgeon training or access to technology, but PCNL is a ubiquitous component of most training programs and very safe. Therefore, so that patients can avoid a major procedure, we would encourage referral to a colleague who specializes in PCNL in situations where a surgeon lacks comfort with or equipment for performing the technique.”

The retrospective study identified patients with staghorn calculi who were seen at Indiana University School of Medicine, Mayo Clinic, Rochester, MN, and British Columbia School of Medicine, Vancouver. The patients who underwent single access PCNL had a mean age of 57 years, 53% were women, and mean body mass index of 32.5 kg/m

Approximately two-thirds of the stones had a Guy’s stone score of 4 and the remaining one-third were Guy’s stone score 3. The median stone burden was 163.4 mm

Mean OR time of 80 minutes for primary PCNL

Mean OR time was 80 minutes for the primary PCNL, and for patients who underwent a secondary PCNL, mean total OR time, including the first procedure, was <200 minutes.

“The secondary procedure rate for patients in our study was relatively high, which is normal, but the total OR time for patients who needed a second procedure was comparable if not less than that of alternate surgical approaches to treat staghorn calculi,” Dr. Large said.

Mean hospital stay for the cohort was 2.3 days, eight patients (2.7%) required an ICU stay, and 15 patients (5.0%) required transfusion. Complications were minimal. Pleural effusion (5.0%) was the most common event followed by fever (2.7%) and sepsis (1.3%). There were no cases of solid organ injury.

Dr. Large acknowledged that the AUA and EAU guidelines identify instances, such as concomitant uretopelvic junction obstruction, where robotic surgery to treat staghorn kidney stones is indicated. He said, however, that the retrospective study he presented supports prior publications recommending that PCNL should be the primary approach for the surgical management of partial and full staghorn stones.

Single-access percutaneous nephrolithotomy can clear the vast majority of staghorn stones with minimal morbidity, said Tim Large, MD, at the 2019 World Congress of Endourology and SWL in Abu Dhabi.

Single-access PCNL feasible for first-line treatment of staghorn calculi

A study of kidney stone patients who were treated using ureteral access sheaths found no evidence of ureteral strictures an average of 4 years following ureteroscopy.

The results are intriguing, given that some urologists believe there are too little data to ascertain whether the use of ureteral access sheaths puts patients at risk of ureteral injury 

 Also notable: The results held true regardless of the diameter of the sheath used, the size of the stone, length of operating time, or gender.

However, given the small sample size-157 patients-“This is an area where more study is needed,” Jose Eduardo Castro Matheus Rodrigues, a research student at the Massachusetts General Hospital department of urology, Boston and a medical student at University of SÃ£o Paulo-Brazil, told AUA 2019 attendees.

The study was conducted under Brian Eisner, MD, of the Massachusetts General Hospital department of urology and Harvard Medical School, Boston.

Results from the study are based on a retrospective review of patients who have undergone ureteroscopy procedures that involved use of a ureteral access sheath. Patients included in the study also had a follow-up visit 1 year or more after the procedure and received an abdominal imaging scan.

While recent studies have shown that placement of ureteral access sheaths during ureteroscopy can cause ureteral lesions, such as when too much force is applied 

 the long-term consequences of deploying ureteral access sheaths are not yet known. This study sought to determine the impact of using ureteral access sheaths on the patient’s chances of developing a ureteral stricture in the first year or more after surgery.

Among the 157 patients who met these criteria, 56% were men and 44% were women, the average age of patients was 61 years (range, 27 to 96 years), and the average follow-up time was 4.1 years (range, 1 to 8 years).

The authors recorded the diameter of the ureteral access sheath used, with 95% of patients being treated with a sheath that had a diameter of 11/13 Fr or larger. The mean diameter of the largest stone removed during ureteroscopy was 6.9 mm (range, 2 to 26 mm), and the average operating time was 31 minutes (range, 10.5 to 108 minutes). Leakage of contrast material was noted in 5% of patients (eight patients).

The authors also noted the types of follow-up imaging used to examine whether use of a ureteral access sheath had caused a ureteral stricture to form. These included renal ultrasound (104 patients), computerized tomography (45 patients), and magnetic resonance imaging (seven patients).

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The results showed that during the patients’ most recent follow-up visit, none of the patients demonstrated persistent hydronephrosis, and no patients had undergone treatment for a ureteral stricture or displayed radiographic evidence of a stricture.

Previous studies on this topic have lacked long-term follow-up data, Rodrigues said. The availability of medium-term follow-up data is critical to advancing discussion around this controversial approach.

Sheath use not linked with strictures

A course of treatment with prednisone may offer improvement in mean total motile count (TMC) for men who undergo vasectomy reversal and subsequently have partial or complete anastomotic obstruction, according to a recent study.

“We wanted to get this study together as the use of prednisone after vasectomy reversal is not uncommon, but the data supporting its use is extremely limited,” G. Luke Machen, MD, told 

. Working with Johnathan Doolittle, MD, and Jay Sandlow, MD, he presented results from a retrospective study at the 2019 AUA annual meeting in Chicago.

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Partial or complete anastomotic obstruction following vasectomy reversal can cause impaired semen parameters, and the authors hypothesized that corticosteroids may be able to reverse early scarring and inflammation involved in the obstruction. They conducted a retrospective review of patients treated between 2008 and 2018; of 368 total vasectomy reversals, they included 89 patients who had received prednisone. The regimen consisted of 2 weeks of prednisone, 20 mg daily followed by 2 weeks of 10 mg daily.

Of the 89 patients, 46 patients underwent a vasovasostomy (VV), 22 underwent a vasoepididymostomy (VE), and 21 underwent a VV/VE. The mean obstructive interval in the full cohort was 7.8 years, and prednisone was started an average of 5.54 months after the vasectomy reversal operation.

The prednisone treatment was associated with a significant improvement in mean TMC. In the full cohort, the mean TMC before prednisone treatment was 3.7 million, compared with 14.2 million after the therapy, for a change of 10.5 million 

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Among the 46 patients who underwent a VV, the mean TMC rose from 6.5 million before prednisone to 19.9 million following the therapy, for an increase of 13.4 million 

=.0012). Among those who underwent a VE procedure, the mean TMC rose from 0.2 million to 8.6 million, for an increase of 8.4 million 

=.2). In those who underwent a VV/VE operation, the mean TMC increased from 1.2 million before prednisone to 7.4 million afterward, for a rise of 6.2 million 

There were 24 patients who were azoospermic at the time of prednisone initiation. Of those, 33.3% saw an improvement in TMC. Among the 65 patients who were not, 76.9% saw an improvement in TMC 

“While not necessarily surprising, I think it’s notable that eight of 24 patients who were azoospermic at the time of initiating prednisone regained sperm in their ejaculate,” said Dr. Machen, a urologist in group practice in Austin, TX.

“This is an especially challenging patient cohort, and if prednisone leads to the return of sperm to the ejaculate, it could save the patient from another operation,” added Dr. Machen, who was a reproductive urology and andrology fellow at the Medical College of Wisconsin, Milwaukee at the time of the study.

The authors noted that it is possible the improvement in semen parameters would have occurred even without the prednisone treatment.

“Based on our results, it seems reasonable to consider a course of prednisone in select patients with suspected partial or complete anastomotic obstruction. However, I would not go so far as to say prednisone should be routinely used post operatively after vasectomy reversal. More well-designed trials are necessary to conclusively determine if the semen parameter improvements seen were the result of the prednisone or simply the result of more time post operatively,” Dr. Machen said.

A course of treatment with prednisone may offer improvement in mean total motile count for men who undergo vasectomy reversal and subsequently have partial or complete anastomotic obstruction, according to a recent study.

Prednisone may improve total motile count post vasectomy reversal

Kidney stone patients take a variety of dietary supplements that claim to treat or prevent kidney stones. While consumer reviews for the supplements tend to be positive, most of the supplements and their ingredients have conflicting or no scientific evidence to support the claims, according to a recent study.

“Patients have been asking my colleagues and me about supplements on the market claiming to treat or prevent kidney stones. What we didn’t know was how many of them there are and what a huge variety of ingredients they contain,” said first author Kevin Koo, MD, MPH, MPhil, instructor of urology and fellow in endourology and minimally invasive urologic surgery at Johns Hopkins University School of Medicine, Baltimore.

“These supplements are readily available at health food stores and online. Online marketplaces like Amazon and Google have made it easier than ever for patients to do a quick search for a supplement or herbal remedy, order it, and start using it without ever really talking to their urologists about it or its expected benefits or risks,” added Dr. Koo, who presented the findings at the 2019 World Congress of Endourology and SWL in Abu Dhabi. The study was subsequently published in the 

Johns Hopkins researchers studied the kidney stone supplement landscape, including marketing tactics used to entice consumers’ use. They also assessed the evidence for ingredients in the supplements to help urologists give patients evidence-based recommendations.

They analyzed a total of 56 nonpharmacologic active ingredients contained in 27 supplements that made specific claims related to kidney stones.

“Many of these supplements claimed to dissolve kidney stones, prevent new stones from forming, or reduce stone-related symptoms,” Dr. Koo said.

Nineteen, or 70%, of the supplements studied claimed they could be used to support kidney health. The average 30-day cost for taking a supplement was $32, and ranged from $4 to $189.

They found that nearly all the products were highly rated, with 21 products having 4- or 5-star ratings (out of 5). Users giving reviews often claimed their stones dissolved or stone pain went away when they took specific supplements. Based on the reviews, patients thinking about using a supplement could think it would be highly effective, Dr. Koo said.

But scientific evidence of their effectiveness was largely nonexistent. The authors’ literature review revealed that of the 56 ingredients studied, 84% had no published studies for use in stone disease; 16%, or nine ingredients, had any published studies for use; and only 9% had studies supporting their use.

In the 18 scientific publications about the ingredients that the authors identified, six showed mixed or no benefit for stone disease; the other 12 publications supported the ingredients’ use in stone formers. Only five were human studies.

Chanca piedra/Phyllanthus niruri showed some evidence of efficacy and was the most studied active ingredient, with human and animal studies. Cranberry, green tea leaf, pomegranate, Tribulus terrestris, and citric acid followed as ingredients with human studies for treating stone disease.

But Dr. Koo said he is hesitant to recommend any supplemental ingredients based on the quality of science available today.

“Even when studies were available, they were often studies done in animals or humans where the outcomes were biochemical changes in the serum or urine-not specifically changes in stone formation or stone recurrence,” Dr. Koo said. “So even with studies that concluded that there might be useful or effective biochemical changes that would potentially lead to decreased stone formation, we don’t know for sure in the vast majority of cases whether consuming that particular ingredient actually results in meaningful changes for our patients.”

Overall, there is very limited evidence, but there are a lot of supplements on the market and patients need to have real expectations of what these supplements may or may not do regardless of their claims, according to Dr. Koo.

“We need to remind our patients that the absence of scientific evidence does not mean an absence of potential harm. In these cases, we simply don’t have definitive studies that allow us to say for sure that using these supplements or using specific ingredients is expected to lead to meaningful changes in stone recurrence or stone formation risk,” he said.

Another message from the study is that urologists should include dietary supplement use when asking patients about other medications they’re taking or have tried for their stone disease.

“We should remind ourselves as clinicians that stone disease is a chronic disease and that the medical and surgical management of stone disease can be very challenging and burdensome for patients. There’s a reason patients look for dietary supplements to help them with their symptoms or with their stone recurrence: Stone disease can create a lot of morbidity and anxiety,” he said. “I think including dietary supplements in our routine counseling can open up an opportunity for a dialogue with the patient about what works, what might work, what doesn’t work, and the evidence behind all the different strategies that our patients might be trying.”

One possible explanation for the positive product reviews is that many supplement labels instruct people to take the products three times per day with 12 ounces of water each time. That’s almost 40 ounces of water, which is about half of what urologists would typically recommend for stone patients to be drinking for fluid intake.

“It’s possible that increased fluid intake is what’s driving some of the user-reported benefits,” Dr. Koo said. 

Providers should incorporate discussion of dietary supplements into patient counseling, Kevin Koo, MD, MPH, MPhil, advises.

Most supplements for stones not backed by science

A significant trend is occurring in the management of urethral stricture, with increased utilization of urethroplasty and decreased utilization of repeat endoscopic procedures, researchers at the University of Washington in Seattle report.

Investigators examined a national sample of patients with employer-based health insurance and found a drastic change in national practice patterns for management of urethral stricture patients, favoring more definitive management in accordance with recently published guidelines.

“The actual AUA guidelines about urethral stricture management weren’t published until 2017, so it’s too early to specifically evaluate the impact of these guidelines on management,” said study investigator Niels V. Johnsen, MD, who was a male genitourinary trauma and reconstruction fellow at the University of Washington at the time of the study. The findings from the current study were presented at the 2019 AUA annual meeting in Chicago.

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Dr. Johnsen and his co-authors examined national trends in urethral stricture management over time utilizing MarketScan, which is a database of employed individuals and their dependents with employer-sponsored health insurance in the U.S. For this investigation, the authors defined repeat endoscopic management as two or more endoscopic procedures per patient. They used the published AUA guidelines as a framework to evaluate what they defined as appropriate surgical management of urethral strictures (a single endoscopic procedure, a single endoscopic procedure followed by urethroplasty if needed, or upfront urethroplasty) compared to inappropriate surgical management (multiple endoscopic procedures).

From 2008 to 2016, which included data on more than 15 million eligible male beneficiaries per year on average, the crude urethroplasty rates per stricture diagnosis had significantly increased by about 44% over the study period, the researchers found.

“More importantly, when we looked at what we defined as ‘appropriate care,’ there has been an 87% increase in appropriate care during the period as well. After adjusting for age and comorbidity status, there was an approximately 18% increased odds of receiving ‘appropriate care’ for each additional year in the study, while older and sicker men remained more likely to undergo endoscopic management as would be assumed,” said Dr. Johnsen, currently assistant professor of urology at Vanderbilt University Medical Center, Nashville, TN.

He said the impetus for this study was that there had been signs within the urology community and some previously published works that the tides were beginning to turn and more urologists were feeling more comfortable performing basic urethroplasty techniques. Over the past decade, a growing body of literature has shown that repeat endoscopic procedures are unlikely to provide good long-term success, resulting in the latest AUA guidelines in 2017.

Dr. Johnsen noted there are some limitations to the current study, including the fact that the authors did not have information as to why patients/providers choose to undergo one management or another.

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“We also do not know if certain individuals were offered a urethroplasty and then opted to undergo repeat endoscopic treatment,” said Dr. Johnsen.

Another limitation is that the definitions of “appropriate” and “inappropriate” care are based on the current guidelines, but not necessarily a reflection of adherence to the guidelines prior to 2017.

This study is important because it shows that nationwide it is becoming less likely that patients will undergo repeat endoscopic management of urethral strictures, suggesting a better understanding by urologists of the low long-term success rates of endoscopic management and relatively higher success rates of urethroplasty, according to Dr. Johnsen.

However, what is driving this evolution is not entirely clear. He said it appears to be due in part to both better data on the relative success rates, as well as increased comfort and distribution of urethroplasty surgical techniques through changes in resident training.

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Findings from a longitudinal cohort study provide an evidence base for counseling patients about pain and recovery following ureteroscopy for nephrolithiasis.

The findings also support the practice of not prescribing narcotics for pain management, reported Justin B. Ziemba, MD, at the 2019 World Congress of Endourology and SWL in Abu Dhabi.

“We know that pain is the most common complaint after ureteroscopy for nephrolithiasis, but we have been lacking good data for counseling patients about this aspect of their recovery,” said Dr. Ziemba, assistant professor of urology in surgery at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

The study was initiated in November 2018 and analyzed data collected for nearly 1 year. English-speaking adults undergoing ureteroscopy for a renal or ureteral stone were eligible for participation. Patients were discharged with a ureteral stent that was removed by post-op day 4. Patients received a non-narcotic regimen for pain control that included ibuprofen, acetaminophen, and tamsulosin (Flomax).

They were asked to complete two generic quality of life instruments, PROMIS-Pain Intensity and PROMIS-Pain Interference, immediately before surgery and on post-op days 1, 7, and 14. Scores are reported compared to the U.S. population mean; a score above 50 indicates that the condition is worse than in the average population.

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“These quality of life instruments can be applied to any disease state, have been rigorously studied and validated in diverse populations, and are benchmarked against a normalized score for the United States general population. Therefore, we hypothesized that these instruments would provide us with reliable information about the severity of postoperative pain and how the pain disrupted participation and engagement in regular activities. It also provides us with a measure of how this compares to a normal population mean,” Dr. Ziemba said.

“In contrast to other studies that have assessed emergency department visits or calls to the office to investigate the impact of postoperative recovery following ureteroscopy, our study evaluates the lived patient experience with respect to pain intensity and interference,” Dr. Ziemba said.

The questionnaires were completed by 101 patients immediately before surgery and by 62, 48, and 21 patients on post-op days 1, 7, and 14, respectively.

Results from the data collected showed that, compared to the U.S. population mean (50), intensity and interference were all clinically and statistically significantly different (Wilcoxon signed rank test; 

<.001) at all time point comparisons except intensity on post-op days 1 and 7 and interference on post-op day 14.

The study also found that for pain intensity, there was a clinically and statistically significant difference from post-op day 0 to 1 (43.8 to 52.1) and from post-op day 7 to 14 (49.1 to 40.5) (Friedman’s 2-way ANOVA; 

<.01). Similarly, for pain interference, there was a clinically and statistically significant difference from post-op day 0 to 7 (56.0 to 62.8) and post-op day 7 to 14 (62.8 to 48.5) (Friedman’s 2-way ANOVA; 

Several factors linked with intensity score

On the first day after surgery, age, gender, first stone, presence of a stent preoperatively, and intraoperative time were significantly associated with intensity score, but only having a preoperative stent and longer intraoperative time were associated with the interference score. By post-op day 7, no significant associations were found between any of the demographic or clinical characteristics and either pain intensity or interference.

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“According to our study, we can now be more confident telling patients that pain intensity is not the driving force of discomfort after surgery, but it is the interference of usual daily activities from the pain that is most pronounced,” said Dr. Ziemba.

“However, the vast majority of people recover quickly, with virtually all reporting pain intensity and interference at or below levels reported by an average American by 14 days after surgery. In addition, the data show that our opioid-free postoperative pain protocol is effective, as pain intensity never increases beyond the level reported by an average American.

Pain interference more pronounced following URS

Bicycling across the globe is increasing as a means of exercise and transportation. Clinicians need to be knowledgeable about the health benefits and risks of cycling so they can educate and care for their patients who ride.

The overall health benefits of cycling are tremendous. Cycling reduces the incidence of cerebrovascular accidents, coronary artery disease, hypertension, dyslipidemia, obesity, and diabetes mellitus. Strong inverse relationships have also been demonstrated between commuter cycling and all-cause mortality, cancer mortality, and cancer morbidity among middle-aged and elderly study participants.

Despite these benefits, cycling commonly leads to injury, with up to 85% of all recreational cyclists citing an overuse injury. Given unbalanced pressure distribution when on the bike, the neck, hands, wrists, lower back, knees, and perineum are the regions most frequently affected by cycling.

Cycling has been associated with genital numbness, priapism, infertility, elevated PSA, erectile dysfunction (ED), lower urinary tract symptoms (LUTS), and prostatitis. Several of the studies that posited these associations, however, were underpowered, did not use validated clinical outcomes, or had insufficient control group comparison. Consequently, the current data on cycling’s impact on urologic and sexual function continues to evolve.

Here, we explore particular aspects of men’s urologic health that are negatively impacted by cycling, review a proposed underlying mechanism of injury, and make specific management suggestions to help prevent cycling-induced genitourinary injury.

Given controversies around the impact of cycling on sexual and urinary wellness, we conducted a large survey study assessing 3,932 male athletes (cyclists, swimmers, and runners) 

 We found that low- and high-intensity cyclists had a higher Sexual Health Inventory for Men (SHIM) score, albeit clinically insignificant, than swimmers or runners. No statistically significant differences were noted between cyclists and non-cyclists in other validated measures of LUTS, including the International Prostate Symptom Score (IPSS) and NIH Chronic Prostatitis Symptom Index (NIH CPSI) (figure 1).

We identify a statistically higher odds of urethral stricture, genital numbness, and saddle sores (OR: 9.8, 

<.001) in cyclists compared to swimmers/runners. Several other large studies corroborate that increased cycling frequency does not increase risk of ED, including the Massachusetts Male Aging Study 

 2014; 11:75-9), the latter of which surveyed 5,282 cyclists. In sum, these studies suggest that 

cycling does not result in worse ED or LUTS compared to swimming or running but may make one more prone to urethral strictures, genital numbness, and saddle sores.

In our cohort, cycling and genital numbness were closely linked 

 Increased years cycling, more frequent weekly cycling, and longer cycling distances per ride were all associated with an increased trend of genital numbness (figure 2). Body mass index and age were not related to odds of genital numbness. Interestingly, in a multivariate regression model with an outcome of ED, there was no statistically significant difference between cyclists with numbness and cyclists without numbness.

When numbness was stratified by anatomic region, cyclists with numbness over the buttock reported statistically worse SHIM scores compared to cyclists without buttock numbness (20.3 v. 18.4, 

<.001). These findings suggest that increased

 cycling may increase risk of inducing perineal numbness, but that itself may not necessarily translate into worsened sexual function.

 Despite an unclear association, it is best to minimize numbness as much as possible while riding.

Microtrauma as potential mechanism of injury

Mechanisms to explain genital numbness in cyclists include perineal vascular compromise and pudendal nerve palsy. While the majority of studies have assessed how cycling affects perineal circulation, less is understood about the potential mechanism of pudendal nerve compromise. Traditional teaching suggests that pudendal nerve palsy is secondary to a static compressive process. However, cycling tends to be a dynamic exercise with constant pressure shifts on the perineum.

We sought to model the trauma a cycling commuter’s perineum experiences by creating a custom bicycle seat that measures pressure changes from simulated road trauma in the lab (figure 3). This is notable as it models real-world cycling where variations in repetitive force from navigating terrain (represented by oscillations in our study) can drive pressure to the pudendal nerve. A heat map of perineal pressure distribution indicated concentration of pressure on the ischial tuberosities and symphysis pubis in women and on the pubic rami in men (figure 4). We found that seat-post shock absorbers significantly decreased perineal pressure (57%-59% decrease, 

In our cohort, even though numbness was not associated with increased ED, it makes sense to avoid numbness when possible. For the hobbyist or more serious cyclist, 

getting your bike professionally fit ensures optimal ergonomics and helps minimize trauma. 

Riding a bike that fits well is likely the single most important step riders can take to protect themselves from genital numbness.

Bicycle modifications can potentially improve genitourinary outcomes after cycling. For example, in our cohort, cyclists who stood more than 20% of the time while cycling and adjusted the handlebar to a height at least even with the saddle had reduced odds of developing genital numbness. Furthermore, we showed that a modified seat decreased traumatic pressures delivered to the perineum.

The overall health benefits of cycling clearly outweigh the risks. With a global obesity epidemic leading to a high prevalence of cardiovascular disease, cycling should be promoted as a healthy form of exercise, transportation and recreation. We still have more to learn about the impact of cycling on urologic wellness in men, but ED appears rare in cyclists and no more common than ED seen in other athletes.

 is associate professor of urology, University of California, San Francisco.

is professor of urology at the Icahn School of Medicine at Mount Sinai and director benign urologic diseases, Mount Sinai Health System, New York. Follow him on Twitter at 

Cycling has multiple benefits, and steps can be taken to prevent genitourinary injury.

Bicycle riding: Good or bad for men’s health?

 Editorial Consultant, is professor of urology, Wake Forest Baptist Medical Center, Winston-Salem, NC.

The new AUA guidelines on surgical management of BPH reflect changes primarily in new minimally invasive approaches to the management of the enlarged prostate. In considering what is new, one should think about indications for a given procedure, the individual patient’s goals, surgeon’s bias and learning curve, availability, and affordability of the technology.

Patient bother with male lower urinary tract symptoms such as slow flow, hesitancy, and sense of incomplete emptying and retention are most common. However, men with overactive bladder, nocturia, post-void dribble, and “older male with prostate” as indications are less responsive to surgical therapy.

Patient factors such as medical risk for anesthesia, use of antiplatelets/anticoagulants, gland size, and gland anatomy play a role in selecting the type of procedure, as do patient expectations, such as desire to maintain antegrade ejaculation at the expense of long-term success, catheter duration, and time from treatment to improvement (transient dysuria/frequency/incontinence/recurrent retention).

Surgeon variables are training and familiarity with a technique, number of patients treated in a month to enhance the learning curve, and desire to be on the forefront. Availability of a team to deal with transient issues post treatment and ability to manage secondary bleeding as well as re-treatment are other variables.   

Availability of new technology is also dependent on clinical setting, such as a trial at a center of excellence or hospital partner/large group willing to support it. The surgeon bias is difficult to assess.

The individual technologies are discussed in the “Hands On” article in this issue (page 1), which mentions enucleation as a technique that needs to be considered when the gland is larger. It appears that many of the ablative technologies such as lasers and the bipolar device can achieve enucleation, albeit some require use of a morcellation device. Added indications for minimally invasive surgical therapies such as large glands and median lobe require an experienced practitioner.

Cost is a hidden factor in the United States and other countries where health insurance covers approved technology but is a real factor where cost is out of pocket. Hospitalization is expensive in the U.S. but a less important factor in other countries. Capital and disposable cost is a factor in low- and middle-income countries where traditional monopolar TURP still rules despite the safety of saline-based ablation devices.

After participating in a number of trials from balloon dilation to water ablation and publishing on them, my conclusion is to do what you know best, learn a new technology from an expert (preferably hands on), and consider participating in a clinical trial (based on patient volume and institutional support). Shorten your learning curve by accumulating cases and doing them in a short time, stay with technology to overcome initial hurdles, and be honest about your outcomes (not what is published in the literature by the expert).

“The expectations of life depend upon diligence; the mechanic that would perfect his work must first sharpen his tools.”-Confucius

"My conclusion is to do what you know best, learn a new technology from an expert, and consider participating in a clinical trial,” writes Gopal H. Badlani, MD.

Alternatives to TURP: Consider these variables

AUA guidelines on benign prostatic hyperplasia (BPH) have evolved with the constantly changing practice of surgical treatment for BPH. Contemporary guidelines were published in 2010, with a necessary validity review being performed in 2014. The most recent AUA BPH guidelines were issued in 2018 and subsequently amended in 2019 to reflect further advancements in the field.

In 2018, important additions to the AUA BPH guidelines focused on both the appropriate pre-procedural diagnostic evaluation and novel surgical enhancements. Available surgical BPH data from 2007 onward were meticulously analyzed and used to develop the current guidelines. All surgical approaches were compared to transurethral resection of the prostate (TURP) as the gold standard.

The guidelines stress a shared decision-making model in which clinicians discuss key treatment classes (medical, minimally invasive, endourologic, open/robotic) and thoroughly review risks and benefits for all treatment options. Patients can then make an informed decision on their selection, which may necessitate a referral to another clinician.

Updated BPH guidelines focusing on medication updates are anticipated in 2021.

The pendulum has swung from the 1960s era where 50% of a urologist’s surgical day involved TURP to a medication-first approach since the development of these drugs in the 1980s. Data from the Medical Therapy of Prostate Symptoms (MTOPS) trial tell us dual medical therapy is an excellent therapy for some men, as they avoid the potential TURP side effects of incontinence, bleeding, or recalcitrant stricture 

Medications are excellent if they have minimal side effects, treat the patient’s lower urinary tract symptoms (LUTS) well, and the patient follows up with his medical care provider to monitor for bladder decompensation. Indeed, pharmacotherapy for BPH has decreased the utilization of surgical intervention in the last 2 decades but has also resulted in surgery being performed more often in older patients with larger glands and inherently higher perioperative risk factors, often including active anticoagulation 

TURP is an excellent therapy but carries the risk of well-known side effects. Patients who undergo surgical intervention earlier for LUTS have greater degrees of improvement than those undergoing late surgical intervention for BPH 

 With the advent of minimally invasive surgical therapy (MIST), BPH treatments with tolerable side effect profiles, minimal anesthesia requirements, and decreased post-procedural sexual dysfunction, surgical intervention can be considered at an earlier time point for patients with BPH.

Initial workup for BPH patients with bothersome LUTS should include a thorough medical history, AUA-Symptom Index, and urinalysis. Patient goals for treatment should be obtained and side effects of various treatment modalities discussed. A recent publication revealed a lack of crucial understanding and patient counseling by urologists and other providers about the potential sexual side effects of medical and surgical BPH management 

 The AUA guideline inclusion of MIST for BPH with sexual side effect-sparing approaches (prostatic urethral lift, water vapor thermal therapy) makes this discussion more relevant.

Guideline amendments have also emphasized the importance of preoperative evaluation of prostatic size to ensure appropriate selection of treatment modality. Again, the new MIST therapies influence workup, as prostate size and anatomy alter treatment options. Ideal imaging in preparation for BPH surgical treatment should include ultrasound of the prostate to afford optimal evaluation of prostatic size along with assessment of a median lobe component of the prostate. Additionally, cystoscopy is recommended, as it affords the clinician important understanding of prostatic urethral anatomy, identification of urethral stricture disease, and assessment of patient tolerance of local anesthesia procedures should the patient desire intervention with MIST. Providers who desire transrectal ultrasound (TRUS) of the prostate and cystoscopy can proceed with both.

Additionally, patients can undergo size assessment with cross-sectional imaging (CT vs. MRI). Providers are encouraged to perform post-void residual, and utilization of pressure flow studies is recommended when the voiding symptoms present diagnostic uncertainty. Urodynamic studies are a reasonable adjunct to guide treatment when patients have neurologic conditions affecting the bladder (multiple sclerosis, Parkinson’s), have failed previous BPH procedures, have a history of pelvic or spinal cord surgery, have had pelvic radiation, or have diabetes. Novel, noninvasive pressure flow studies utilizing a penile cuff while voiding have demonstrated a 92% positive predictive value and sensitivity of 75% in detecting bladder outlet obstruction when compared to formal catheter-based pressure flow studies 

The updated BPH guidelines remind us that TURP either with monopolar or bipolar energy remains an excellent treatment approach. As a point of reference, a recent Canadian registry study of nearly 46,000 TURPs from 2003 to 2016 revealed a transfusion rate of 2.6%, 30-day ER visit rate of 22.5% with approximately half being admitted, a stricture/bladder neck contracture rate of 11.2%, and a surgical retreatment rate of 10.9% at a median follow-up of 4.42 years 

 These numbers are important to keep in mind as patients begin to choose from a menu of options that minimize certain side effects, perhaps at the expense of treatment durability.

 (PUL [UroLift]) can be considered as an option for LUTS from BPH in men who have prostate glandular size of 30-80 grams and absence of a median lobe (Moderate Recommendation, Evidence Level C). As recently as January 2020, PUL gained FDA approval for glandular size of up to 100 grams. No studies that met eligibility criteria attempting to utilize PUL for the median lobe or sized 80-100 grams were available at the time of guideline publication. Prostatic urethral lift utilizes a minimally invasive, office-based approach to resolve prostatic urethral bilobar hyperplasia with mechanical clips providing treatment of outlet obstruction (figure).

Patients who request intervention with prostatic urethral lift should be advised that improvement in symptoms and flow rate are decreased as compared to transurethral resection of the prostate 

 Prostatic urethral lift can be offered to patients who have concerns of ejaculatory function, as it is likely to have little impact on a patient’s erectile or ejaculatory function 

 Indeed, prostatic urethral lift remains a good option for the patient with mild to moderate LUTS with BPH without a median lobe component in whom sexual health and functionality are a priority in the treatment setting.

The updated guidelines focus on appropriate pre-procedure evaluation and novel surgical enhancements, according to Matthew D. Houlihan, DO, and Tobias S. Köhler, MD, MPH.

Vol 48 No 3