Focal High-Intensity Focused Ultrasound vs. Active Surveillance for ISUP Grade 1 Prostate Cancer: Medium-Term Results of a Matched-Pair Comparison.

INTRODUCTION/BACKGROUND: Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa. MATERIALS AND METHODS: We included 2 non-randomized prospective series of 132 (fHIFU) and 421 (AS) consecutive patients diagnosed with ISUP 1 PCa between 2008 and 2018. A matched pair analysis was performed to decrease potential bias. Study main outcomes were freedom from radical treatment (RT) or androgen-deprivation therapy (ADT), treatment-free survival (TFS), time to metastasis, and overall survival (OS). RESULTS: Median fHIFU follow-up was 50 months (interquartile range, 29-84 months). Among matched variables, no major differences were recorded except for AS having more suspicious digital rectal examination findings (P = .0074) and recent enrollment year (P = .0005). Five-year intervention-free survival from RT or ADT was higher for the fHIFU cohort (67.4% vs. 53.8%; P = .0158). Time to treatment was approximately 10 months shorter for AS than for fHIFU (time to RT, P = .0363; time to RT or ADT, P = .0156; time to any treatment, P = .0319). No differences were found in any-TFS (fHIFU, 61.4% vs. AS, 53.8%; P = .2635), OS (fHIFU, 97% vs. AS, 97%; P = .9237), or metastasis (n = 0 in fHIFU and n = 2 in AS; P = .4981). Major complications (≥ Clavien 3) were rare (n = 4), although 36.4% of men experienced complications. No relevant changes were noted in continence (P = .3949). CONCLUSION: At a 4-year median follow-up, fHIFU for mainly low-risk PCa (ISUP grade 1) is safe, may decrease the need for radical treatment or ADT and may allow longer time to treatment compared to AS. Nonetheless, no advantages are seen in PCa progression and/or death (OS).

The key role of levator ani thickness for early urinary continence recovery in patients undergoing robot-assisted radical prostatectomy: A multi-institutional study.

BACKGROUND: Urinary continence (UC) recovery dramatically affects quality of life after robot-assisted radical prostatectomy (RARP). Membranous urethral length (MUL) has been the most studied anatomical variable associated with UC recovery. OBJECTIVE: To investigate whether levator ani thickness (LAT), assessed with multi-parametric magnetic resonance imaging (mpMRI), correlates with UC recovery after RARP. DESIGN, SETTING, AND PARTICIPANTS: The study included 209 patients treated with RARP by expert surgeons with extensive robotic experience from 2017 to 2019. All patients had complete, clinical, mpMRI, pathological, and postoperative data including pelvic floor muscle training (PFMT) protocols. INTERVENTION: After a radiologist-specific training, two urologists independently examined the files, blinded to clinical and pathological findings as well as to postoperative continence status. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: On mpMRI, LAT, bladder neck (BN) shape, MUL, and apex overlapping (AO) were measured. UC recovery was defined as use of 0 or 1 safety pad at follow-up. Multivariable models were used to assess the association between variables and UC recovery. RESULTS AND LIMITATIONS: Overall, 173 (82.8%) patients were continent after a median follow-up of 23 months (interquartile range [IQR]: 17-28). Of these, 98 (46.9%) recovered within 3 months after surgery, 42 (20.1%) from 3 to 6 months, and 33 (15.8%) from 6 months onwards. A significant higher rate of patients with LAT > 10 mm (88.1 vs.75.8%; p = 0.03) experienced UC recovery, compared to those with LAT < 10 mm. This difference was observed in the first 3 months after surgery. At multivariable analysis, LAT (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 1.02-1.37; p = 0.02), Preoperative ICIQ score (OR: 0.91, 95% CI: 0.82-0.98, p = 0.03) and PFMT (OR: 1.98, 95% CI: 1.01-3.93; p = 0.04) independently predict higher UC recovery within 3 months, after accounting for age, BMI, preoperative PSA, D'Amico risk group, MUL, BN shape and AO. CONCLUSIONS: LAT greater than 1 cm was associated with greater UC recovery. Specifically, LAT greater than 1 cm seems to be associated with higher UC rate at 3 months after RARP, compared to those with LAT < 1 cm. PATIENT SUMMARY: Magnetic resonance features can help in predicting the risk of incontinence after robot-assisted radical prostatectomy and should be taken into account when counseling patients before surgery.

Long-term Outcomes of Focal Cryotherapy for Low- to Intermediate-risk Prostate Cancer: Results and Matched Pair Analysis with Active Surveillance.

BACKGROUND: To date, only one trial compared focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). In addition, long-term outcomes of focal cryotherapy (FC) are lacking. OBJECTIVE: Our aim was to evaluate long-term outcomes of FC and compare them with AS. DESIGN, SETTING, AND PARTICIPANTS: We included two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008-2018) for low- to intermediate-risk PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Study outcomes were radical therapy-free or androgen deprivation therapy (ADT)-free, any treatment-free, metastasis-free, and overall survival. A matched pair analysis was performed using seven covariates. RESULTS AND LIMITATIONS: The median FC follow-up was 85 mo (interquartile range 58-104); 92 (76%) men had International Society of Urological Pathology (ISUP) grade 1. Among matched variables, no significant differences were present except for cT stage and year of entry (both p < 0.01). Ten-year radical therapy-free or ADT-free, any treatment-free, metastasis-free, and overall survival were 51%, 40.2%, 93.9%, and 97%, respectively for FC. No differences were noted with AS (all p > 0.05), with the exception of time to radical therapy, time to radical therapy and ADT, and time to any treatment, all being shorter for AS (all p < 0.01). Freedom from radical treatment or ADT was higher for FC (AS 10 yr 39.3%; p = 0.04). Complications were relatively rare (26.5%) and mainly of low grade (Clavien >2, n = 3); three men developed incontinence (p = 0.0814), while both International Index of Erectile Function 5 and International Prostate Symptom Score scores increased (p = 0.0287 and p = 0.0165, respectively). Limitations include absence of randomization. CONCLUSIONS: At an early long-term follow-up, FC in the context of mainly low-risk PCa is safe and increases time to radical therapy but does not provide meaningful oncological advantages compared with AS. PATIENT SUMMARY: We compared focal cryotherapy with active surveillance mainly for low-risk prostate cancer. Focal cryotherapy, despite having fewer complications, did not yield meaningful advantages over active surveillance at 10 yr. Active surveillance should be preferred to focal cryotherapy for these patients.

Trends in reported male sexual dysfunction over the past decade: an evolving landscape.

We investigated changes in patterns of reported male SDs at a single academic centre over a 10-year time frame. Comprehensive data of 2013 patients consecutively assessed for the first time by a single Sexual Medicine expert between 2006 and 2019 has been analysed. All patients were assessed with a thorough sexual and medical history. Primary reason for seeking medical help at first assessment was recorded for all patients and categorized as: erectile dysfunction (ED), premature ejaculation (PE), low/reduced sexual desire/interest (LSD/I), Peyronie's disease (PD), and other SDs. Linear and logistic regression models tested the association between different reasons for seeking medical help and the time at first evaluation. Local polynomial regression model explored the probability of reporting different SDs over the analysed time frame. Median (IQR) age at first clinical assessment was 50 (38-61) years. Overall, most patients were assessed for ED (824; 41%), followed by PD (369; 18%), PE (322; 16%), LSD/I (204; 10%) and other SDs (294; 15%). Significant changes in terms of reported SD over the analysed time frame were observed. The likelihood of assessing patients for ED significantly increased up to 2013, with a decrease in the past 5 years (p < 0.001). PE assessment at presentation linearly decreased over time (OR: 0.94; 95% CI: 0.91-0.96; p < 0.001). Patients assessed during the past few years were more likely to report PD (OR: 1.20; 95% CI: 1.15-1.25; p < 0.001) and LSD/I (OR: 1.21; 95% CI: 1.16-1.26; p < 0.001), with a linear increase over the evaluated time frame. Likewise, patients were also more likely to report other SDs (Coeff: 1.06; 95% CI: 1.02-1.10; p = 0.004), with a linear increase over time. These results may reflect real changes in SD incidence, increased public awareness towards different SDs and the possible impact of novel treatments available on the market throughout the same time frame.

Serum testosterone levels are not associated with the severity of penile curvature in men with Peyronie's disease-findings from a cross-sectional study.

We aimed to evaluate the relationship between serum testosterone (T) levels and penile curvature in a cohort of men presenting for chronic phase Peyronie's disease (PD). Clinical data from 149 patients assessed for chronic phase PD between 2016 and 2019 at a single academic center were analyzed. Deformity assessment was conducted during an intracavernosal injection-induced rigid erection. Both total T (tT) and calculated free T (cFT) were assessed in every patient and considered as continuous variables or according to quartiles of the normal range. Hypogonadism was defined for tT < 10.4 nmol/L. Descriptive statistics and linear regression models tested the association between T values and the severity of penile curvature. Overall, median tT value was 15.9 (11.4-20.8) nmol/L in the whole cohort; median curvature magnitude and plaque size were 45 (30-60) degrees and 1.5 (0.8-2.0) cm, respectively. Penile curvature (40.0 vs. 45.0 degree; p = 0.7) and plaque size (1.5 vs. 1.3 cm; p = 0.4) were similar between eugonadal and hypogonadal patients. The magnitude of penile curvature did not differ across tT quartiles (p = 0.31). Both at univariable (ß 1.32; p < 0.01) and multivariable (ß 1.34; p < 0.01) linear regression model, only duration of PD was associated with the severity of penile curvature magnitude. The results of this cross-sectional study confirmed that there is no association between serum T values and the severity of penile curvature in patients with chronic phase PD. Only PD duration is associated with penile deformity severity.

SHBG levels in primary infertile men: a critical interpretation in clinical practice.

OBJECTIVE: We aimed to test the association between age, BMI and sex-hormone-binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple's infertility. DESIGN: Retrospective study. METHODS: Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (<33, 33-41, >41 years) and BMI as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG. RESULTS: Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P < 0.001). For each year increase in age, SHBG increased 0.32 nmol/L; conversely, for each unit increase in BMI, SHBG decreased by 1.1 nmol/L (all P < 0.001). SHBG levels decline with increasing BMI was greater than SHBG progressive increase with age. Overall, BMI explained 3.0 times more of the variability in SHBG than did ageing. At multivariate linear model, age and BMI were the most significant factors influencing SHBG concentration (all P < 0.001), after accounting for CCI, albumin levels and smoking status. CONCLUSIONS: We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

Robotic surgery in patients with achondroplastic dwarfism: evaluation of risks and issues in an anatomical challenging bilateral partial nephrectomy.

The reports on the performance of robotic surgery in patients with dwarfism are anecdotal; anesthesiological issues and a challenging anatomy are the main factors that lead most of surgeons to prefer a more traditional approach. We present a case of bilateral robotic partial nephrectomy in a patient affected by achondroplastic dwarfism and aim to evaluate risks and issues in this type of surgery.

Multiple PDE5Is use as a marker of decreased overall men's health: A real-life study.

Erectile dysfunction (ED) is considered a sentinel marker for poor general men's health status. Severe ED has been associated with poor response to phosphodiesterase type 5 inhibitors (PDE5Is) therapy. We sought to assess the association of multiple PDE5Is prescription with the overall patients' health status. Socio-demographic and clinical variables from 939 consecutive white-European, heterosexual, sexually-active men seeking medical help for ED at same tertiary-referral academic outpatient clinic were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients have been stratified into naïve and non-naïve according to their history of previous prescriptions of any PDE5I. Every patient completed the International Index of Erectile Function (IIEF) questionnaire. Logistic regression models tested the association between patients' baseline characteristics (thus including previous PDE5Is prescriptions) and the overall health status. Overall, 328 (35%) patients were non-naïve for PDE5Is. Of them, 172 (52%), 99 (30%), and 57 (17%) had been prescribed with 1, 2 or 3 different PDE5Is, respectively. Naïve and non-naïve patients did not differ in terms of age, BMI, baseline ED severity; conversely, non-naïve patients had a higher CCI score. At logistic MVA, the number of PDE5Is prescriptions emerged as an independent predictor of a higher burden of comorbidities regardless of ED severity; the higher the number of PDE5Is prescriptions, the higher the CCI score (OR 1.69, 2.49, and 2.90 for 1, 2 or 3 previous PDE5Is, respectively), after accounting for age, BMI, baseline ED severity and cigarette smoking. More than a third of patients seeking medical help for ED at a single tertiary-referral center were non-naïve for PDE5Is. The increasing number of previous prescriptions of PDE5Is emerged as a worrisome marker of a poorer overall men's health status regardless of ED severity.

Temporal Trend in Incidental Prostate Cancer Detection at Surgery for Benign Prostatic Hyperplasia.

OBJECTIVE: To assess changes in the rate of incidental prostate cancer (PCa) after benign prostatic hyperplasia (BPH) surgery over the last decade. MATERIALS AND METHODS: We identified 1177 patients surgically treated for BPH (open prostatectomy, transurethral resection or holmium laser enucleation [HoLEP] of the prostate) in 2007-2016 at a single European academic center. Local polynomial regression was used to explore changes in the rate of incidental PCa detected after BPH surgery and of preoperative biopsy performed over time. Logistic regression analyses tested the association of incidental PCa diagnosis with year of surgery and preoperative biopsy. RESULTS: Incidental PCa was found in 6.4% (74) of cases, 67 (91%) with Grade group 1 disease. We observed an increased incidence of PCa diagnosis after BPH surgery over time (odds ratio [OR]: 1.12; 95%confidence interval [CI]: 1.02-1.24, P = .02) along with a concomitant decrease in the rate of preoperative prostate biopsies (OR: 0.83; 95%CI: 0.79-0.88, P < .0001). Patients undergoing a preoperative biopsy showed a lower risk of being diagnosed with PCa after surgery (OR: 0.29; 95% CI: 0.12, 0.72 P = .007). Patients treated with HoLEP had a higher chance of incidental PCa detection (OR: 2.28; 95%CI: 1.30-4.00; P = .004), although this may be related to the significantly higher number of HoLEP performed over the last years. CONCLUSION: The increased rate of low-risk PCa detected after BPH surgery in the last decade reflects the clinical practice changes in PCa screening and diagnosis leading to a reduced number of unnecessary biopsies and indolent cancer diagnosis.

Medical treatment of erectile dysfunction: too many medical prescriptions?

Erectile dysfunction (ED) is a worldwide commonly reported condition; epidemiological data showed a prevalence ranging from 2.3 to 53.4% within different population subsets. In this context, the advent of phosphodiesterase type 5 inhibitors (PDE5is) in the second mid of 1990s has deeply changed the treatment scenario of this bothersome condition. Being user-friendly compounds with an excellent overall safety profile, PDE5is emerged as the first-line treatment for ED, thus overcoming topical alprostadil and intracavernous injections (ICIs). However, available data on treatment-utilization patterns and medical prescriptions of PDE5is showed a range of as wide as 22-78% of patients reporting to purchase PDE5is even without a proper medical prescription. Moreover, an increase in the recreational use of PDE5is among young men has been observed in the last decades, with a worrisome diffusion of potential health-risky behaviours associated with this habit. Indeed, treatment of ED should carefully follow internationally based clinical guidelines to avoid inappropriate drug prescriptions, which may eventually expose treated patients to drug-related side effects. Thereof, a careful assessment of the so-called modifiable and reversible ED risk factors along with a patient-tailored screening for potential contraindications to the treatment itself should be performed in every case. Lastly, although conclusive data still lack, the potential association between life-risky PDE5is side effects (i.e. cardiovascular adverse events, melanoma skin cancer and worsening of prostate cancer outcomes) should be carefully taken into account when counselling patients for ED treatment.