Erection hardness score or penile Doppler ultrasound: which is a better predictor of failure of nonsurgical treatment of erectile dysfunction?

Background: In the evaluation of men presenting for erectile dysfunction (ED), specific diagnostic tests, such as an intracavernous injection test (IIT) with Erection Hardness Score (EHS) assessment or penile Doppler ultrasound (PDU), may be necessary. Aim: The study sought to compare the prognostic value of PDU parameters with erection rigidity with EHS during IIT in predicting refractory ED after 5 years. Methods: Patients referred for ED were evaluated and had a PDU with at least 15 µg of intracavernous alprostadil and without any sexual stimulation. At 5 years of follow-up, current and past ED treatments were noted. Refractory ED was defined as having a penile prosthesis (PP) implanted, having failed nonsurgical treatments but having refused PP implantation, or having discontinuation of nonsurgical treatments due to loss of efficacy. Patients with hypogonadism and pelvic surgery were excluded. Receiver-operating characteristic curves were drawn and the area under the curve (AUC) was calculated. Outcomes: The outcome was the AUC for predicting refractory ED. Results: At 5 years, 69 men were still in follow-up with a mean age of 58.47 ± 10.39 years, and 13 (18.8%) were classified as having refractory ED. The AUC for the EHS, peak systolic velocity, end-diastolic flow, and resistive index to discriminate refractory ED were 0.820, 0.613, 0.730, and 0.714, respectively. Clinical Implications: EHS can be a good predictor of response to nonsurgical treatments in ED. Strengths and Limitations: This was a prospective study to compare IIT with PDU, and validated disease-specific questionnaires were used to assess both clinical efficacy and satisfaction. PDU was performed by a blinded third party. However, resulting from a single-center study, our sample size can be considered small, and the number of events observed was also low. Conclusion: Our data suggest that an abnormal EHS during an IIT is, at least, noninferior than an abnormal PDU in predicting those patients that will not respond to nonsurgical treatments and that will need a PP in long-term.

Microbiota of Urine, Glans and Prostate Biopsies in Patients with Prostate Cancer Reveals a Dysbiosis in the Genitourinary System.

Prostate cancer (PCa) is the most common malignant neoplasm with the highest worldwide incidence in men aged 50 years and older. Emerging evidence suggests that the microbial dysbiosis may promote chronic inflammation linked to the development of PCa. Therefore, this study aims to compare the microbiota composition and diversity in urine, glans swabs, and prostate biopsies between men with PCa and non-PCa men. Microbial communities profiling was assessed through 16S rRNA sequencing. The results indicated that α-diversity (number and abundance of genera) was lower in prostate and glans, and higher in urine from patients with PCa, compared to non-PCa patients. The different genera of the bacterial community found in urine was significantly different in PCa patients compared to non-PCa patients, but they did not differ in glans and prostate. Moreover, comparing the bacterial communities present in the three different samples, urine and glans show a similar genus composition. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed significantly higher levels of the genera Streptococcus, Prevotella, Peptoniphilus, Negativicoccus, Actinomyces, Propionimicrobium, and Facklamia in urine of PCa patients, whereas Methylobacterium/Methylorubrum, Faecalibacterium, and Blautia were more abundant in the non-PCa patients. In glans, the genus Stenotrophomonas was enriched in PCa subjects, while Peptococcus was more abundant in non-PCa subjects. In prostate, Alishewanella, Paracoccus, Klebsiella, and Rothia were the overrepresented genera in the PCa group, while Actinomyces, Parabacteroides, Muribaculaceae sp., and Prevotella were overrepresented in the non-PCa group. These findings provide a strong background for the development of potential biomarkers with clinical interest.

Prognostic Value of Bladder Involvement in the Outcome of Upper Tract Urothelial Carcinoma.

Accurately predicting the clinical prognosis of upper tract urothelial carcinoma (UTUC) seems crucial. We evaluated the effect of the involvement of urothelial bladder carcinoma (UBC) as a potential prognostic factor for overall survival (OS) and progression-free survival (PFS). The cohort included 115 patients with UTUC, subgrouped between January 2009 and December 2019 as follows: (1) only UTUC and (2) UTUC with synchronous or metachronous UBC (UTUC + UBC). Univariate and multivariate analyses were performed to identify independent prognostic factors for OS and PFS. Synchronous or metachronous UBC diagnosis in UTUC patients was an independent predictor of worse PFS (HR 3.326 CI 95% 1.474−7.503, p = 0.004), but it was not identified as a prognostic factor for OS (p > 0.05). Lymphovascular invasion (LVI) was associated with decreased PFS (HR 2.687 CI 95%1.172−6.163, p = 0.020) and OS (HR 4.980 CI 95%1.763−14.064, p = 0.002). This study indicates that concomitant or later UBC could predict a poor PFS, but it is not associated with a significantly worse OS in UTUC patients. The prognostic impact of LVI underlines its inclusion in the tumor staging system of UTUC.

Can we rely on total testosterone measurement to exclude hypogonadism in erectile dysfunction?

Although male hypogonadism (MH) is a prevalent comorbidity in patients presenting for erectile dysfunction (ED), its screening relies solely on total testosterone (TT). Ageing and other conditions can increase sex hormone-binding globulin (SHBG) and lower free testosterone (FT) causing symptomatic MH despite normal TT. The primary objective was to measure the prevalence of normal TT/low FT among patients presenting for ED. From January 2019 to December 2020, 408 patients referred for sexual dysfunction were screened; 180 men with a confirmed diagnosis of ED were included. MH was screened using TT, SHBG, albumin and LH. FT was calculated (cFT). Low TT, high SHBG and low cFT were defined as <345 ng/dL, >50 nmol/L and <6.5 ng/dL, respectively. Patients were divided into groups according to TT/cFT status and to age group. The frequency of normal TT/low cFT was 17.2%. From all 31 patients with normal TT/low cFT, only four (12.9%) had either hyperthyroidism, hepatic disease or HIV infection, while 23 (74.2%) were older than 60 years. Patients with normal TT/low cFT were older (65.57 ± 10.43 vs. 56.79 ± 10.63 yo, p = 0.001) and had higher SHBG (78.48 ± 40.14 vs. 52.35 ± 20.39 nmol/L, p = 0.014) than patients with normal TT/cFT. Patients over 60 years represented 48.9% of the sample, 52.5% had elevated SHBG and their frequency of normal TT/low cFT was 26.3%. Normal TT/low cFT is frequent and can be missed by current screening recommendations for MH in patients presenting for ED. Ageing seems to be the main culprit as elevated SHBG prevalence increases steeply after the sixth decade. TT cannot solely be relied on to exclude biochemical MH in patients presenting for ED, especially in patients over 60 years old. Current guidelines for MH screening in ED should be amended.

Current stepwise recommendations for hypogonadism screening in erectile dysfunction are not cost-effective.

Hypogonadism is a prevalent comorbidity with erectile disfunction (ED) and current guidelines recommend screening for hypogonadism with total testosterone (TT). If low TT is detected, further assessment with LH and SHBG plus albumin are needed to establish an etiology and treatment. Our primary objective was to determine the cost benefit of current stepwise approach versus ad initium full hormonal assessment. Two hundred consecutive male patients referred for ED were screened after consent and 81 were included and assessed for hypogonadism according to the current stepwise approach with TT, and only if TT was less than 345 ng/mL, a full hormonal assessment with TT, LH, and SHBG plus albumin to calculate free testosterone was performed. Direct costs were calculated using the national public healthcare system reimbursement tables and were compared with a hypothetical initial full hormonal assessment. Screening TT was less than 345 ng/mL in 34.6% patients leading to a full hormonal assessment on these. Using a stepwise approach there was a direct cost increase of 5.82 € per patient. Moreover, one out of every three patients had two extra venipunctures and an additional follow-up appointment. Current stepwise recommendations may prove costly in high prevalence scenarios such as the ED subpopulation as a direct cost increase was observed.

Is There a Point to Performing a Penile Duplex Ultrasound?

INTRODUCTION: Specialized diagnostic evaluation of erectile dysfunction (ED) may require an intracavernous injection test (IIT) or penile duplex ultrasound (PDU). AIM: Our primary objective was to compare the prognostic value of IIT and PDU for treatment efficacy and patient satisfaction with first-line sildenafil citrate. METHODS: After 200 patients were screened, a total of 77 patients with ED had a standardized PDU by a blinded third party, and peak systolic velocity (PSV), end diastolic flow (EDF), and resistive index (RI) in timely intervals were recorded. The erection hardness score (EHS) was used to score erection rigidity during the test and was also noted. Patients also completed a briefed International Index of Erectile Function (IIEF-5) questionnaire and were started on open-label 100 mg sildenafil citrate at baseline. The IIEF-5 and erectile dysfunction inventory of treatment satisfaction (EDITS) questionnaires were repeated and completed at 6 months' follow-up. Improvement, cure, and satisfaction were defined as an increase of 4 points in IIEF-5 with an IIEF-5 score higher than 21 points and EDITS score higher than 50, respectively. Receiver operating characteristic curves were drawn and the area under the curve (AUC) was calculated and compared. MAIN OUTCOME MEASURE: EHS did not have a different or larger AUC than PSV, EDF, and RI for improvement, cure, and satisfaction with sildenafil citrate. RESULTS: The patient's mean age was 58.76 ± 10.27 years and almost half of the patients had moderate ED according to the IIEF-5 (42.8%). Improvement, cure, and satisfaction were high among participants (77.9%, 64.9%, and 67.5%, respectively). The erection rigidity EHS also showed an excellent-to-good ability to predict improvement, cure, and patient satisfaction (AUC = 0.921, 0.873, and 0.898, respectively) with sildenafil citrate. CLINICAL IMPLICATIONS: There is no point in performing more than an IIT when a specialized diagnostic evaluation is required for diagnostic or medico-legal reasons because PDU is time-consuming and requires both hardware and ultrasound skills with no added prognostic value. STRENGTHS AND LIMITATIONS: This is the first prospective study to directly compare IIT with PDU, and validated disease-specific questionnaires were used to assess both clinical efficacy and satisfaction. Moreover, the PDU was performed by a blinded third party. However, this was a single-center study and the population included was small. CONCLUSION: PDU parameters add no prognostic value to determining erection rigidity during a standard IIT. Erection rigidity during IIT, as assessed with the EHS, suffices as a prognostic tool. Morgado A, Diniz P, Silva CM. Is There a Point to Performing a Penile Duplex Ultrasound? J Sex Med 2019;16:1574-1580.

Is there a role for bilateral peak systolic velocity readings in a penile duplex ultrasound?

The penile duplex ultrasound (PDU) has been used as a diagnostic tool in erectile dysfunction (ED) management. It is currently recommended that peak systolic velocity (PSV) and end-diastolic flow (EDF) should be recorded on both the right and left cavernosal arteries. However, the clinical utility of bilateral recordings is unknown. Our primary objective is to assess the clinical utility of bilateral recordings in ED treatment with sildenafil. A total of 77 patients were included. All patients had a standardised PDU and also completed the IIEF-5 and started on-demand treatment with sildenafil at 100 mg at baseline. The IIEF-5 and EDITS were completed at the 6-month follow-up. The Spearman test was used to assess correlation. Receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) was calculated. Improvement, cure and satisfaction were high (77.9%, 64.9% and 67.5%, respectively), and the median IIEF-5 and EDITS were 25(22; 25) and 81.81(63.63; 88.63) respectively. The lowest PSV had the highest positive correlation with IIEF-5 and EDITS (p = 0.436 and 0.379, respectively), and it could predict improvement, cure and satisfaction with a fair-to-good accuracy (AUC = 0.837, 0.750 and 0.749 respectively). The present study shows bilateral penile blood-flow assessment is important, and attention should be focused on the lowest bilateral PSV.

Misdiagnosis And Undertreatment Of Erectile Dysfunction In The Portuguese Primary Health Care.

INTRODUCTION: The importance of erectile dysfunction (ED) diagnosis and treatment has been highlighted since the early 2000s. However, nearly 20 years after the first phosphodiesterase 5 inhibitor (PDE5i) was marketed, underdiagnosis and undertreatment of ED in the primary health care setting may still be present. AIM: To assess the relative frequency of patients who are medically treated for ED before referral to specialized urology care. The secondary objectives were to evaluate possible reasons for non-treatment prior to referral and other signs of undertreatment, namely cardiovascular risk assessment and antihypertensive treatment. METHODS: 200 male patients referred for ED to specialist urology care by general practitioners were screened after consent between January 2016-December 2018. A full standardized medical and sexual history were taken. Previous medical treatment of ED, namely pharmacologic name and dosages, and cardiovascular risk factors were noted. MAIN OUTCOME MEASURES: Of the 115 included patients, only 33.9% of patients had already taken PDE5i before referral, and none had taken alprostadil by intracavernous route. RESULTS: The mean patient age was 58.68 ± 10.01 years old. Only 45.2% had been prescribed the highest dose of PD5i. From the remaining untreated patients, only 19.7% had ≥3 cardiovascular risk factors, including 5.6% of patients who also presented moderate-to-severe stable or unstable angina requiring a stress test or cardiology assessment before treatment. Regarding the 54 patients with medical history of arterial hypertension, 43.4% and 30.2% were treated for hypertension with a diuretic and a beta blocker, respectively. CONCLUSION: More focus on the primary healthcare continuous medical education regarding sexual dysfunction, namely ED, is needed because major undertreatment of ED is still present because low prescription of PD5i before referral is noted. Morgado A, Moura ML, Dinis P, et al. Misdiagnosis And Undertreatment Of Erectile Dysfunction In The Portuguese Primary Health Care. Sex Med 2019;7:177-183.

Use of botulinum toxin for genitourinary conditions: What is the evidence?

Botulinum toxin A is licensed for the treatment of urinary incontinence due to neurogenic detrusor overactivity (NDO) and overactive bladder (OAB). Only onabotulinumtoxinA has at this moment such approval, in NDO at a dose of 200 U and in OAB at a dose of 100 U. Regulatory phase 3 trials have been carried out in both conditions. In NDO it was shown to decrease urinary incontinence, to improve urodynamic parameters and to increase quality of life in multiple sclerosis and spinal cord injured patients. Adverse events included urinary tract infections and necessity of de novo clean intermittent catheterization, which occurred mainly in patients with multiple sclerosis. In OAB patients with urge incontinence, onabotulinumtoxinA decreased urinary incontinence and micturition frequency while improving quality of life. Again, main adverse events were urinary tract infections and transient urinary retentions. Long-term studies in both NDO and OAB demonstrate the efficacy and safety of the treatment. Available phase 3 trials of onabotulinumtoxinA in benign prostatic hyperplasia did not show any relevant efficacy in improving lower urinary tract symptoms.

Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard?

PURPOSE OF REVIEW: The pharmacological treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) is based on alpha-blockers and 5α-reductase inhibitors isolated or in combination. Silodosin, an alpha-1A specific alpha-blocker is the only innovation in these groups of agents. This classical paradigm is being challenged by antimuscarinics, 5-phosphodiesterase inhibitors (PDE5i) and ß3-adrenoreceptor agonists. RECENT FINDINGS: Silodosin is effective in reducing BPH/LUTS, including nocturia and shows little cardiovascular adverse events. Antimuscarinic drugs isolated or in combination with alpha-blockers improve storage symptoms without any harmful effect to the voiding function. PDE5i alone improve BPH/LUTS. Combination of PDE5i with alpha-blockers provides better symptomatic control than alpha-blockers alone. A recent head-to-head comparison of tadalafil 5 mg/day with tamsulosin 0.4 mg/day showed that these agents provided the same improvement in BPH/LUTS and, surprisingly, the same improvement in the urinary flow. In fact, previous studies with tadalafil had not shown any effect of tadalafil on flow. In addition, tadalafil but not tamsulosin improved sexual function. Mirabegron, the first ß3-adrenoreceptor agonist, while improving BPH/LUTS in men with bladder outlet obstruction, do not decrease urinary flow or detrusor pressure. SUMMARY: The standard medical treatment for BPH/LUTS is still based on alpha-blockers, 5ARIs or its combination. In the future, it is expected that BPH/LUTS treatment will become individualized, according to the type of symptoms, presence of sexual dysfunction and risk of BPH progression. This will challenge our concept of standard treatment for BPH/LUTS.

Botulinum toxin treatment for bladder dysfunction.

Botulinum toxin A is available under three different protein complexes that are not interchangeable until appropriate comparative studies are undertaken. The best studied for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity and overactive bladder/idiopathic detrusor overactivity is onabotulinum toxin A. This brand is only approved for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity at a dose of 200 U and idiopathic detrusor overactivity at a dose of 100 U. In patients with detrusor overactivity as a result of spinal cord injury or multiple sclerosis, 200 U of onabotulinum toxin A should be injected in 30 different sites above the trigone. It was shown to be highly effective in curing or decreasing urinary symptoms of incontinence, increasing quality of life, increasing bladder capacity and decreasing maximal detrusor pressure. This effect was independent of the concomitant use of oral anticholinergic drugs. Adverse events were mild, mainly urinary tract infections and high postvoid residual requiring clean intermittent catheterization. In patients with overactive bladder/idiopathic detrusor overactivity, 100 U of onabotulinum toxin A should be injected in 20 sites above the trigone. It markedly decreases urinary incontinence and improves quality of life. Frequency and urgency episodes are also decreased. Adverse events are mild, mainly urinary tract infections and urinary retention. The latter occurred in just 5% of the patients. Candidates for onabotulinum toxin A treatment should be warned that the effect of the toxin is transient and that repeated injections will be required to maintain the effect in the long term. There is no evidence that repeated injections will have a decreased efficacy.

Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.

UNLABELLED: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems. OBJECTIVE: • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control. METHODS: • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50 mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index. RESULTS: • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P = 0.02). • The number of patients with an IPSS change of ≥ 3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P = 0.02). • Both treatments were safe and well tolerated. CONCLUSIONS: • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.

Trigonal injection of botulinum toxin A in patients with refractory bladder pain syndrome/interstitial cystitis.

BACKGROUND: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease without an effective treatment, characterized by pain during bladder filling. Most nociceptive bladder afferents course in the trigone. OBJECTIVE: To evaluate efficacy and tolerability of trigonal injection of botulinum toxin A (BoNTA) in patients with BPS/IC. Urine concentration of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were also evaluated. DESIGN, SETTING, AND PARTICIPANTS: Women with refractory BPS/IC were included in an open, exploratory study. INTERVENTION: Under sedation, 100 U of BoNTA (Botox) were injected in 10 trigonal sites (10 U per 1 ml saline). Retreatment was allowed 3 mo after injection. MEASUREMENTS: Pain, urinary frequency, O'Leary-Sant score (OSS), quality of life, (QoL), and urodynamic testing at 1 and 3 mo and every 3 mo thereafter. Urine NGF and BDNF were assessed at the same points. Patients who were retreated were evaluated every 3 mo. RESULTS AND LIMITATIONS: All patients reported subjective improvement at 1- and 3-mo follow-up. Pain, daytime and nighttime voiding frequency, OSS, and QoL improved significantly. Bladder volume to first pain and maximal cystometric capacity more than doubled. Treatment remained effective in >50% of the patients for 9 mo. Retreatment was also effective in all cases, with similar duration. A significant, transient reduction in urinary NGF and BDNF was observed. No cases of voiding dysfunction occurred. The low number of patients and the lack of a placebo arm are obvious limitations of this study. CONCLUSIONS: Trigonal injection of BoNTA is a safe and effective treatment for refractory BPS/IC.

Has botulinum toxin therapy come of age: what do we know, what do we need to know, and should we use it?

PURPOSE OF REVIEW: To review the most recent data concerning the clinical use of botulinum toxin type A (BoNT/A) in different human lower urinary tract dysfunctions, with particular emphasis on neurogenic detrusor overactivity. RECENT FINDINGS: The most recent findings indicate that the repeated application of BoNT/A is effective in patients with neurogenic detrusor overactivity, maintaining sustained control of incontinence, protection of upper urinary tract and reduction of urinary infectious complications. In addition, BoNT/A injections have proved to be well tolerated and the risk of bladder fibrosis nonexistent. Other BoNT/A indications under investigation are idiopathic detrusor overactivity, benign prostatic enlargement and bladder pain syndrome/interstitial cystitis. SUMMARY: Although still waiting for approval, BoNT/A detrusor injections can be safely offered to well informed patients with refractory neurogenic detrusor overactivity, as an alternative to more invasive therapies, such as bladder augmentation. Ongoing studies are expected to come up with the necessary information for definitive approval of BoNT/A in neurogenic detrusor overactivity patients. Regarding other possible applications such as idiopathic detrusor overactivity, benign prostatic enlargement and bladder pain syndrome/interstitial cystitis, its use should still be restricted to research centres in well designed clinical trials.