Andrew D. Bowser

β3 agonist treatment of overactive bladder (OAB) may also improve erectile dysfunction (ED) in men who have symptoms of both disorders, according to study results reported at the 2020 Sexual Medicine Society of North America (SMSNA) 21st Annual Fall Scientific Meeting.

Five of 13 men with OAB and mild to moderate ED experienced clinically relevant increases in erectile function after 12 weeks of treatment with mirabegron (Myrbetriq), a β3-adrenoceptor agonist approved by the FDA for treatment of OAB. As expected, symptoms of OAB also improved, with no serious adverse events noted over 12 weeks, said Serkan Karakus, MD, a clinical fellow with the James Buchanan Brady Urological Institute at Johns Hopkins School of Medicine in Baltimore, Maryland.

“This is a single-arm, observational study and small study group, but we found some promising results,” Karakus said in an interview. “So I think we could move forward to larger, randomized studies.”

These preliminary findings at least suggest that mirabegron could be an alternative for ED treatment when phosphodiesterase type 5 (PDE5) inhibitor treatment fails or is contraindicated, according to coinvestigator Arthur L. Burnett II, MD, MBA, a professor of urology at Johns Hopkins School of Medicine.

“The question is whether have we solved ED treatment entirely with PDE5 inhibitors, and the answer is no,” Burnett said in an interview. “So why not explore alternative mechanisms with a thought that this new therapy, which may not necessarily be addressing a predominant mechanism of penile erection, could still be a complementary or additive therapy to consider.”

In his SMSNA presentation, Karakus described OAB and ED as disorders of the lower genitourinary tract that share several pathophysiologic mechanisms, including dysregulation of the nitric oxide-cyclic guanosine monophosphate pathway, increased sympathetic tone, upregulation of Rho kinase expression, and chronic hypoxia.

The β3 adrenoceptor has been found in human corpus cavernosum, he added, noting that mirabegron could act simultaneously in the bladder and corpus cavernosum via β3-adrenoceptor activation.

The nonrandomized, single-arm study by Karakus and colleagues included 20 men with OAB and mild to moderate ED as defined by International Index of Erectile Function (IIEF) Erectile Function domain scores between 11 and 25 or Sexual Health Inventory for Men (SHIM) scores between 8 and 21. Patients received mirabegron 25 mg daily for 2 weeks and then 50 mg daily for the next 10 weeks.

Seven patients were lost to follow-up, and 13 remained in the study for the full 12 weeks, according to investigators. Treatment with mirabegron was associated with significant improvements in mean SHIM scores through week 4 and week 8 (

=.0003). The SHIM score decreased slightly by week 12, so no significant improvement was noted at that time, according to Karakus.

However, looking at individual SHIM scores, 5 of 13 patients experienced a 4-point increase at 12 weeks, and there were no clinically relevant decreases in SHIM or IIEF scores for any patient.

IIEF scores trended toward significant improvement at week 4 and week 8 evaluations (

=0.08), and no changes were seen in orgasmic function or sexual desire.

As anticipated, treatment with mirabegron significantly improved symptoms of OAB and OAB-related quality of life, according to the investigators. In addition, no serious adverse events were observed; transient nonserious adverse events included headache, constipation, back or leg pain, flu-like symptoms, rash, and elevated blood pressure, Karakus said.

According to Burnett, senior author of the study, these findings support continued investigation of the safety and efficacy of mirabegron in men with OAB and concurrent ED.

“This is not a definitive study, it’s not a randomized controlled trial, and the numbers aren’t there that need to be done,” Burnett said. “But I think it does provide some interesting initial observations to test the hypothesis and possibly will be a foundation to move forward with something more rigorous to come.”

Disclosure: Astellas Pharma US, Inc provided funding for the study.

1. Karakus S, Musicki B, Burnett AL. Mirabegron for erectile dysfunction. Abstract presented at: 2020 Sexual Medicine Society of North America 21st Annual Fall Scientific Meeting; November 9-15, 2020; virtual.

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The findings support continued investigation of the safety and efficacy of mirabegron in men with OAB and concurrent ED, says study author Arthur L. Burnett, II, MD, MBA.

Mirabegron may improve erectile dysfunction in men with overactive bladder symptoms

Use of a novel penile traction device significantly increased penile length and preserved erectile function in men who have undergone a prostatectomy, an investigator reported at the 2020 Sexual Medicine Society of North America Annual Fall Scientific Meeting.

Men using the RestoreX (PathRight Medical) traction device saw a median 1.6-cm increase in length at 6 months, versus a median of 0.3 to 0.7 cm for controls in the randomized, open-label study, according to David Yang, MD, andrology fellow at Mayo Clinic, Rochester, Minnesota.

Patients reported no change in erectile function at 6 months, and noted a slight improvement in satisfaction compared to decreases in both of those end points in the control arm, Yang said of the study, which has accrued 82 patients, including 55 who had reached 6-month follow-up at the time of this report.

Although larger numbers of patients and external studies are needed to validate the results, Yang said the current findings suggest RestoreX penile traction therapy may be a promising approach for improving penile length, spontaneous erections, and sexual satisfaction without the need for use of on-demand therapy with a phosphodiesterase 5 (PDE 5) inhibitor.

“This is the first noninvasive treatment option in the postprostatectomy setting that has randomized controlled evidence of improvements in both erectile function and penile length, so hopefully this will drive further research and protocols for penile rehabilitation,” Yang said.

Previous research demonstrated that RestoreX penile traction therapy improved penile curvature, length, and erectile functioning in men with Peyronie disease, according to Yang.

In a randomized, single-blind, controlled trial reported by Mayo Clinic investigators in 2019 in the 

 110 men were randomized 3:1 to penile traction therapy or a control group. Using the device 30 to 90 minutes per day for 3 months not only improved curvature in 77%, but also significantly improved erectile function as measured by the International Index of Erectile Function (IIEF) questionnaire, and increased penile length by 1.6 cm versus 0 cm in controls.

“Seeing that improvement in penile length led us towards this study looking at use of RestoreX in the postprostatectomy setting, because a common complaint between these 2 patient populations is loss of penile length,” said Yang, who was a coinvestigator in the Peyronie disease study.

Loss of penile length and erectile dysfunction are very common after prostatectomy, according to Yang, who said in his virtual SMSNA presentation that 15% to 68% of men report loss of penile length post prostatectomy.

“Prior studies looking at penile rehabilitation (post prostatectomy) have not demonstrated with high-level data any significant benefit of PDE 5 inhibitors, or vacuum devices for erectile function recovery,” he added.

Unique features of RestoreX include secure clamping of the penis and the ability to adjust traction without removing the device, Yang said.

To evaluate the efficacy of RestoreX in the postprostatectomy setting, Yang and colleagues initiated a randomized, controlled trial of 82 men (mean age, 58 years), including 55 patients for whom 6-month follow-up data were available as of this report.

At 1 month post prostatectomy, the men were randomly allocated to a control arm, or 1 of 2 penile traction therapy arms (30 minutes 5 times a week or 60 minutes 7 times a week) for 5 months, followed by a 3-month open-label phase.

At 6 months, a statistically significant increase in median penile length was observed in the traction group versus the control group, according to the investigators. Patients using traction had a 1.6-cm increase in length as measured to the corona, compared to 0.3 cm in the control group (

 < .01). Likewise, the traction patients had a 1.6-cm length increase as measured to the tip, compared to 0.7 cm in the control group (

More than 50% of traction patients said they were satisfied with their penile length at 6 months, compared to 11% in the control arm (

Significant differences were seen in both erectile function and intercourse satisfaction favoring the patients treated with RestoreX, according to Yang. The RestoreX group saw no change from baseline to 6 months in the erectile function domain of the IIEF, whereas scores decreased in the control group. Intercourse satisfaction measured by IIEF increased slightly in the traction patients, compared to a decrease in the control arm.

Eighty-seven percent of men treated with RestoreX said they would use the device again, whereas 13% said they were unsure, according to the report.

No major adverse events were reported among any of the 55 patients with 6-month follow-up, according to Yang.

Beyond Peyronie disease and the postprostatectomy setting, RestoreX is also being evaluated in a randomized controlled trial including men with diabetes. Preliminary data, also reported at the 2020 SMSNA meeting,

 included statistically significant improvements in penile length, suggesting the traction device could be a viable approach to a common and difficult-to-treat problem, according to Yang and coinvestigators.

1. Yang D, Ziegelmann M, Manka M, et al. Efficacy of RestoreX penile traction therapy in improving penile length and erectile function post prostatectomy. Abstract presented at: 2020 Sexual Medicine Society of North America Annual Fall Scientific Meeting; November 9-15, 2020; Virtual. Session 5.

2. Ziegelmann M, Savage J, Toussi A, et al. Outcomes of a novel penile traction device in men with Peyronie’s disease: a randomized, single-blind, controlled trial. 

 2019;202(3):599-610. doi:10.1097/JU.0000000000000245

3. Yang D, Ziegelmann M, Manka M, et al. Use of RestoreX penile traction therapy for treatment of penile length loss in diabetic men. Abstract presented at: 2020 Sexual Medicine Society of North America Annual Fall Scientific Meeting; November 9-15, 2020; Virtual. Session 4.

Men using the RestoreX traction device saw a median 1.6-cm increase in length at 6 months, versus a median of 0.3 to 0.7 cm for controls.

Penile traction therapy improves post-prostatectomy penile length, erectile function

The largest analysis of active surveillance for metastatic renal cell carcinoma (RCC) presented to date shows that a proportion of patients can be safely observed without need to start systemic therapy right away.

The median time on active surveillance exceeded 14 months for patients starting systemic therapy at least 6 months after diagnosis in the study, based on patients with metastatic RCC in the Canadian Kidney Cancer information system (CKCis).

Overall survival was significantly longer in the 863-patient active surveillance cohort as compared to a group of 848 patients receiving immediate treatment, according to investigator Igal Kushnir, MD, a medical oncology fellow at Ottawa Hospital Cancer Centre in Ottawa, ON. The study was presented at the American Society of Clinical Oncology annual meeting in Chicago.

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According to Dr. Kushnir, these new findings corroborate and strengthen the conclusions of a 

 study (2016; 17:1317-24) and a presentation from the 2018 ASCO annual meeting that suggested the benefit and safety of selective active surveillance in smaller cohorts.

Surveillance now ‘supported with robust evidence’

“It’s something that is easier to endorse, because now it’s supported with robust evidence, and we can reassure the patient that it’s safe,” Dr. Kushnir said in an interview with 

When exactly to utilize active surveillance still relies on the “art of oncology,” said Dr. Kushnir, who noted he and co-authors looked further and couldn’t find an obvious clinical marker-such as histology, International Metastatic RCC Database Consortium (IMDC) risk criteria, or metastatic burden-that predicted the benefit of the approach in the CKCis cohort.

Nevertheless, patients can probably be selected for active surveillance based on the rate of disease change seen in early serial imaging, according to Dr. Kushnir.

“Our guess is that if you have a patient that has no symptomatic disease, no pending visceral crisis, and the overall burden of disease is not high, it’s probably safe to defer treatment to at least the next serial imaging. If the growth kinetics on the next imaging are quite low, then probably this patient can be assigned to active surveillance,” said Dr. Kushnir, who worked on the study with M. Neil Reaume, MD, and co-authors.

To assess the outcomes and safety of active surveillance versus immediate systemic treatment, Dr. Kushnir and colleagues identified patients in the CKCis database diagnosed with metastatic RCC between 2011 and 2016.

They classified active surveillance as either starting systemic treatment at least 6 months after a diagnosis of metastatic RCC, which included 370 patients, or never starting systemic therapy at all, provided overall survival was greater than 1 year (to exclude patients likely not receiving treatment due to poor prognosis), which included 493 patients.

Among the 370 patients who did start systemic treatment 6 or more months after the active surveillance period, the median time on active surveillance was 14.2 months, with a range of 6 to 71 months, Dr. Kushnir reported.

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The 5-year probability of overall survival was 70.2% for the active surveillance cohort versus 32.1% for the immediate treatment group 

<.0001). After adjusting for age and IMDC risk criteria, both overall survival and time to treatment failure were significantly greater in the active surveillance patients who later started systemic treatment, as compared to those who had immediate treatment, according to his report.

Taken together, these findings suggest a significant number of patients can be safely observed for a long period of time, sparing both medical and financial toxicities associated with systemic therapy for a median of more than a year, Dr. Kushnir said.

“After a median follow-up of 41 months, still 57% of patients on active surveillance never received systemic therapy, which is quite significant,” he added.

Dr. Kushnir has stock or other ownership interests with Teva Pharmaceutical Industries Ltd. Several of his co-authors also reported disclosures; for a full list, go to 

The largest analysis of active surveillance for metastatic renal cell carcinoma presented to date shows that a proportion of patients can be safely observed without need to start systemic therapy right away.

Surveillance safe for some mRCC patients

A new investigational diagnostic imaging technique based on analyzing nanoscale resolution maps of cell surfaces performed favorably compared to what might be expected with cystoscopy in detecting 

Proceedings of the National Academy of Sciences

When evaluating five cells per patient urine sample, the modality had 94% diagnostic accuracy in the identification of individuals who did or did not have cancer, according to study author Igor Sokolov, PhD, of Tufts University, Boston.

The technique, which involves machine-learning analysis of images obtained using atomic force microscopy (AFM), offered a statistically significant improvement in diagnostic accuracy versus cystoscopy, according to the investigators, who described a study that involved analysis of cells from bladder cancer patients and control subjects.

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While further research is needed, this noninvasive imaging technique might one day provide an alternative diagnostic approach that avoids the discomfort and expense associated with cystoscopy, and may have utility in cancers of the upper urinary tract or urethra, Dr. Sokolov said in an interview.

“The methodology is applicable to pretty much any cancer where we can get cells without tissue biopsy. It’s definitely much more preferable to biopsy for the patient-if you spit, spill, or cough out some cells, we can analyze them,” he told 

In the present study, Dr. Sokolov and colleagues evaluated urine samples from 25 patients with pathologically confirmed bladder cancer and 43 individuals with no present evidence of bladder cancer. The cells were collected similar to what’s done in voided urine cytology, according to investigators.

The cells were evaluated with AFM, in which the movements of a tiny cantilever are recorded as it passes over the surface-in this case, the surface of a cell. Those measurements are displayed as images that reflect certain physical properties, such as height, and force of adhesion between the sample and the tip of the cantilever that is in contact with the sample.

The AFM images were analyzed using computer-based machine learning methods designed to recognize different objects and patterns, according to Dr. Sokolov.

The accuracy of the modality was 94%, with sensitivity/specificity pairs of 81/98% and 91/82% in example analyses, Dr. Sokolov and colleagues reported in the journal.

The AFM-based noninvasive analysis was significantly better than what has been reported for cystoscopy, according to results of a statistical analysis. Using area under the receiver operating characteristic curve (AUC) for classification, AFM and cystoscopy had AUCs of 0.92 and 0.77, respectively 

Marital status linked to bladder Ca survival

Results of the AFM-based modality also compare favorably with the accuracy of currently used noninvasive modalities for detecting bladder cancer based on urine samples, such as immunocytochemistry, genetic analysis using fluorescence in situ hybridization, and NMP22 biomarker evaluation, which have reported sensitivities of 20% to 80% in this setting, according to Dr. Sokolov.

The research was supported in part by the National Science Foundation and Norris Cotton Cancer Center, Dartmouth College. Tufts University has applied for a patent related to the atomic force microscopy machine learning technology, invented by Dr. Sokolov and Milos Miljkovic, PhD, a co-author of the paper.

A new investigational diagnostic imaging technique based on analyzing nanoscale resolution maps of cell surfaces performed favorably compared to what might be expected with cystoscopy in detecting bladder cancer.

Andrew D. Bowser

Articles

Mirabegron may improve erectile dysfunction in men with overactive bladder symptoms

Penile traction therapy improves post-prostatectomy penile length, erectile function

Surveillance safe for some mRCC patients

Noninvasive bladder Ca test performs favorably compared to cystoscopy