Medium-term follow up of active surveillance for early prostate cancer at a non-academic institution.

OBJECTIVES: To report oncological outcomes of active surveillance (AS) at a single non-academic institution adopting the standardised Prostate Cancer Research International Active Surveillance (PRIAS) protocol. PATIENTS AND METHODS: Competing risk analyses estimated the incidence of overall mortality, metastases, conversion to treatment, and grade reclassification. The incidence of reclassification and adverse pathological findings at radical prostatectomy were compared between patients fulfilling all PRIAS inclusion criteria vs those not fulfilling at least one. RESULTS: We analysed 341 men with Grade Group 1 prostate cancer (PCa) followed on AS between 2010 and 2022. There were no PCa deaths, two patients developed distant metastases and were alive at the end of the study period. The 10-year cumulative incidence of metastases was 1.9% (95% confidence interval [CI] 0.33-6.4%). A total of 111 men were reclassified, and 127 underwent definitive treatment. Men not fulfilling at least one PRIAS inclusion criteria (n = 43) had a higher incidence of reclassification (subdistribution hazards ratio 1.73, 95% CI 1.07-2.81; P = 0.03), but similar rates of adverse pathological findings at radical prostatectomy. CONCLUSION: Metastases in men on AS at a non-academic institution are as rare as those reported in established international cohorts. Men followed without stringent inclusion criteria should be counselled about the higher incidence of reclassification and reassured they can expect rates of adverse pathological findings comparable to those fulfilling all criteria. Therefore, AS should be proposed to all men with low-grade PCa regardless of whether they are followed at academic institutions or smaller community hospitals.

Which patient may benefit the most from penile prosthesis implantation?

BACKGROUND: Penile prosthesis implantation has been associated with overall good functional outcomes. Of relevance, some patients reported higher level of satisfaction and quality of life. AIM: We investigated the profile of the patients who may benefit the most from penile prosthesis implantation. MATERIALS AND METHODS: Data from a national multi-institutional registry of penile prostheses including patients treated from 2014 to 2017 in Italy (Italian Nationwide Systematic Inventarization of Surgical Treatment for Erectile Dysfunction) were analyzed. All data have been prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and revised by a single data manager. Patients' baseline characteristics were recorded. In order to simultaneously evaluate perceived penile prosthesis function and quality of life, all patients were re-assessed at 1-year follow-up using the validated questionnaire Quality of Life and Sexuality with Penile Prosthesis. High quality of life after surgery was defined as a score higher than the 75th percentile in each of the subdomains of the Quality of Life and Sexuality with Penile Prosthesis questionnaire. Logistic regression analysis tested the association between clinical characteristics and high quality of life after penile prosthesis implantation. RESULTS: Follow-up data were available for 285 patients (median age 60 years; interquartile range: 56-67) who underwent penile prosthesis implantation. Erectile dysfunction etiology was organic in 40% (114), pelvic surgery/radiotherapy in 39% (111), and Peyronie's disease in 21% (60) of the cases. Patients showed good overall Quality of Life and Sexuality with Penile Prosthesis scores at 1-year follow-up for functional (22/25), personal (13/15), relational (17/20), and social (13/15) domains. Overall, 27.0% (77) of patients achieved scores consistent with the high quality of life definition. These patients did not differ in terms of median age (60 vs. 62), type of prosthesis (inflatable penile prostheses: 95% in both of the cases), and post-operative complications (10% vs. 14%) than those with lower quality of life score (all p > 0.1). At logistic regression analysis, erectile dysfunction etiology was the only factor independently associated with high quality of life at 1 year after surgery (p = 0.02). Patients treated for Peyronie's disease (odds ratio: 2.62; p = 0.01; 95% confidence interval: 1.20-5.74) were more likely to report better outcomes after accounting for age, post-operative complications, and surgical volume. CONCLUSION: Penile prosthesis implantation is associated with an overall good quality of life. The subset of patients affected by erectile dysfunction secondary to Peyronie's disease seemed to benefit the most from penile prosthesis implantation in terms of functional outcomes, relationship with their partners and the outside world, and perceived self-image. The systematic use of validated questionnaires specifically addressed at evaluating quality of life and satisfaction after penile prosthesis implantation should be further implemented in future studies to better define the predictors of optimal satisfaction after penile prosthesis implantation.

The Accuracy of Transurethral Bladder Resection in Detecting Bladder Cancer Histological Variants and Their Prognostic Value at Radical Cystectomy.

OBJECTIVES: to investigate the accuracy of transurethral resection of bladder tumours (TURBT) in detecting histological variants (BHV) at radical cystectomy (RC) and to evaluate the impact of TURBT before cystectomy on oncological outcomes. METHODS: Data of 410 consecutive RCs were assessed. Positive and negative predictive values were used to assess the accuracy of TURBT in detecting BHV. Cohen's Kappa coefficient was used to calculate the agreement grade. Logistic regression analysis predicted features based on the presence of BHV at TURBT. Multivariable backward conditional Cox regression analysis was used to estimate oncological outcomes. RESULTS: A total of 73 patients (17.8%) showed BHV at TURBT as compared to 108 (26.3%) at RC. A moderate agreement in histological diagnosis was found between TURBT and RC (0.58). However, sensitivity and specificity in detecting BHV were 56% and 96%, respectively. Furthermore, positive predictive value (PPV) was 84.7% and negative predictive value (NPV) was 84.6%. Presence of BHV at TURBT was an independent predictor for pathologic upstage, albeit not a predictor for positive nodes or positive surgical margins. However, at multivariable analysis adjusted for all confounders, presence of BHV at TURBT was an independent predictor for recurrence after RC, but not for survival. Conversely, the presence of BHV at RC was an independent predictor for both recurrence and survival. CONCLUSION: There was a moderate agreement between TURBT and RC histopathological findings. TURBT, alone, could not provide an accurate and definitive histological diagnosis. Detection of BHV in TURBT specimens is not an independent predictor of oncological outcomes; indeed, only pathological features at RC are associated with worse survival. However, BHV presence in cystectomy specimens resulted as an independent predictor of both cancer-specific and overall mortality.

Oncological outcomes of concomitant carcinoma in situ at radical cystectomy in pure urothelial bladder cancer and in histological variants.

INTRODUCTION: The presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants. METHODS: We evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage. RESULTS: Median age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease). Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomy Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants. CONCLUSION: Concomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.

The impact of histological variants on outcomes after open radical cystectomy for muscle-invasive urothelial bladder cancer: results from a single tertiary referral centre.

OBJECTIVES: To evaluate the impact of histological variants on oncological outcomes of patients with muscle-invasive bladder cancer treated with open radical cystectomy and furthermore to determine any association between survival and each histotype of bladder cancer. MATERIALS AND METHODS: Data from 525 consecutive patients with muscle-invasive bladder cancer treated with radical cystectomy between January 2008 and May 2019 were collected retrospectively. The Kaplan-Meier curves and multivariable analysis addressed the role of histological variants in recurrence, cancer-specific and overall mortality between all subgroups. RESULTS: Of 525 patients, 131 (25.0%) showed a histological variant at radical cystectomy. With a median follow-up of 31 months, 209 (39.8%) recurrences, 184 (35.0%) cancer-related deaths and 260 (49.5%) overall deaths were reported. The presence of histological variant was associated with advanced tumour stage, the presence of concomitant carcinoma in situ, lymph node metastasis, lymphovascular invasion and positive surgical margins compared to pure urothelial bladder cancer (all p values < .008) and resulted as an independent risk factor for cancer-specific mortality (p = 0.001). Patients with a histological variant were at significantly higher risk for recurrence, cancer-specific mortality and overall mortality (all p values ≤ .001). Micropapillary, sarcomatoid or small cell differentiation was associated with reduced survival. CONCLUSION: The presence of histological variants at radical cystectomy seems to be weakly associated with reduced survival compared to pure urothelial bladder cancer paired for pathologic stage. The association of histological variants with advanced and biologically aggressive tumours suggests the need for attention on the overall management of these patients, in particular for micropapillary, sarcomatoid and small cell differentiation.

The Use of Multiparametric Magnetic Resonance Imaging for Follow-up of Patients Included in Active Surveillance Protocol. Can PSA Density Discriminate Patients at Different Risk of Reclassification?

INTRODUCTION: The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy. MATERIALS AND METHODS: Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies + systematic random biopsies. Different PSAD cutoff values were tested (< 0.10, 0.10-0.20, ≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates. RESULTS: One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD < 0.10 ng/mL2; 16%, 25%, 36%, and 44%, in case of PSAD 0.10 to 0.19 ng/mL2; and 25%, 42%, 55%, and 67% in case of PSAD ≥ 0.20 ng/mL2. PSAD ≥ 0.20 ng/mL2 (odds ratio [OR], 2.45; P = .007), PI-RADS 3 (OR, 2.47; P = .013), PI-RADS 4 (OR, 2.94; P < .001), and PI-RADS 5 (OR, 3.41; P = .004) were associated with a higher risk of reclassification. CONCLUSION: PSAD ≥ 0.20 ng/mL2 may improve predictive accuracy of mpMRI results for reclassification of patients in AS, whereas PSAD < 0.10 ng/mL2 may help selection of patients at lower risk of harboring clinically significant prostate cancer. However, the risk of reclassification is not negligible at any PSAD cutoff value, also in the case of mpMRI(-).

Multiparametric magnetic resonance imaging and clinical variables: Which is the best combination to predict reclassification in active surveillance patients?

INTRODUCTION & OBJECTIVES: We tested the role of multiparametric magnetic resonance imaging (mpMRI) in disease reclassification and whether the combination of mpMRI and clinicopathological variables could represent the most accurate approach to predict the risk of reclassification during active surveillance. MATERIALS & METHODS: Three-hundred eighty-nine patients (pts) underwent mpMRI and subsequent confirmatory or follow-up biopsy according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Pts with negative (-) mpMRI underwent systematic random biopsy. Pts with positive (+) mpMRI [Prostate Imaging Reporting and Data System, version 2 (PI-RADS-V2) score ≥3] underwent targeted + systematic random biopsies. Multivariate analyses were used to create three models predicting the probability of reclassification [International Society of Urological Pathology ≥ Grade Group 2 (GG2)]: a basic model including only clinical variables (age, prostate-specific antigen density, and number of positive cores at baseline), an Magnetic resonance imaging (MRI) model including only the PI-RADS score, and a full model including both the previous ones. The predictive accuracy (PA) of each model was quantified using the area under the curve. RESULTS: mpMRI negative (-) was recorded in 127 (32.6%) pts; mpMRI positive (+) was recorded in 262 pts: 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. At a median follow-up of 12 months, 125 pts (32%) were reclassified to GG2 prostate cancer. The rate of reclassification to GG2 prostate cancer was 17%, 35%, 38%, and 52% for mpMRI (-), PI-RADS 3, 4, and 5, respectively (P < 0.001). The PA was 69% and 64% in the basic and MRI models, respectively. The full model had the best PA of 74%: older age (P = 0.023; Odds ratio (OR) = 1.040), prostate-specific antigen density (P = 0.037; OR = 1.324), number of positive cores at baseline (P = 0.001; OR = 1.441), and PI-RADS 3, 4, and 5 (overall P = 0.001; OR = 2.458, 3.007, and 3.898, respectively) were independent predictors of reclassification. CONCLUSIONS: Disease reclassification increased according to the PI-RADS score increase, at confirmatory or follow-up biopsy. However, a no-negligible rate of reclassification was found also in cases of mpMRI (-). The combination of mpMRI and clinicopathological variables still represents the most accurate approach to pts on active surveillance.

Extended pelvic lymph node dissection during radical prostatectomy: comparison between initial robotic experience of a high-volume open surgeon and his contemporary open series.

BACKGROUND: The aim of this study was to evaluate intra- and perioperative outcomes of a single high volume open radical prostatectomy (ORP) surgeon, during his learning curve period for robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). METHODS: The study included 264 intermediate-high risk prostate cancer patients, treated by ORP + ePLND or RARP + ePLND, prospectively collected. Descriptive statistics compared clinical and pathological variables between groups. Bivariate (Pearson) correlation analysis assessed the relationship between the number of lymph node (LN) removed, positive surgical margins (PSM), surgical time and the number of procedures performed per group. RESULTS: pT stage and Gleason score (GS) were lower in RARP than in ORP group (both P=0.04), while PSM were more frequent in the RARP group (40% vs. 25%; P=0.02). However, PSM decreased with the increase of RARP procedures. The number of LNs removed was 25 and 22, in RARP and ORP group (P=0.03). However, LN+ rate did not differ between groups (11% vs. 16%; P=0.216). In the RARP group, overall surgical time and ePLND time decreased with the increase of surgical procedures (all P<0.001). CONCLUSIONS: RARP requires significant learning curve to reduce operative room time and obtain PSM comparable to those of an ORP high-volume surgeon. On the contrary, the quality of ePLND during RARP seems to be not related to the number of procedures performed, allowing removal of a number of LNs that is clinically comparable to ORP.

Difference in Frequency and Distribution of Nodal Metastases Between Intermediate and High Risk Prostate Cancer Patients: Results of a Superextended Pelvic Lymph Node Dissection.

Objectives: To evaluate the frequency and distribution of pelvic nodes metastases, in intermediate-high risk prostate cancer (PCa) patients (pts), who underwent open radical prostatectomy (ORP) and superextended pelvic lymph node dissection (sePLND). Patients and Methods: We retrospectively evaluated 630 consecutive pts with clinically localized, intermediate-high risk PCa, treated with ORP and sePLND from 2009 to 2016 at a single institution. The sePLND always removed all nodal/fibro-fatty tissue of the internal iliac, external iliac, obturator, common iliac, and presacral regions. Results: Positive lymph nodes (LN+) were found in 133 pts (21.1%). The median number of removed nodes and LN+ was 25 and 1, respectively. LN+ were found in 64 (48.1%), 58 (43.6%), 53 (39.8%), 16 (12%), and 20 (15%) pts and were present as a single site in 27 (20.3%), 22 (16.5%), 20 (15%), 0, and 6 (4.5%) cases in the internal iliac, external iliac, obturator, common iliac, and presacral chain, respectively. An ePLND would have correctly staged 127 (95%) pts but removed all LN+ in only 97 (73%) pts. Presacral nodes harbored LN+ in 20 patients. Among them, 18 were high-risk patients. Moreover, all but 1 pts with common iliac LN+ were in high risk group. Conclusions: These results suggest that removal of presacral and common iliac nodes could be omitted in intermediate risk pts. However, a PLND limited to external iliac, obturator, and internal iliac region may be adequate for nodal staging purpose, but not enough accurate if we aim to remove all possible site of LN+ in high risk pts.

Perioperative and Oncologic Outcomes of Nephrectomy and Caval Thrombectomy Using Extracorporeal Circulation and Deep Hypothermic Circulatory Arrest for Renal Cell Carcinoma Invading the Supradiaphragmatic Inferior Vena Cava and/or Right Atrium.

BACKGROUND: Radical nephrectomy (RN) and caval thrombectomy (CT) for renal cell carcinoma, with extracorporeal circulation (ECC) and deep hypothermic circulatory arrest (DHCA) is a challenging surgical approach. OBJECTIVE: To assess peri-operative and oncologic outcomes of renal cell carcinoma patients treated with RN and CT, using ECC and DHCA. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively evaluated 46 patients who underwent RN and CT using ECC and DHCA. SURGICAL PROCEDURE: After retroperitoneal nodal dissection and RN, a cardiopulmonary bypass was placed and DHCA achieved. A combined approach through the abdomen and the thorax was described. MEASUREMENTS: Perioperative and long-term survival outcomes were reported. RESULTS AND LIMITATIONS: Median operative time and length of hospital stay were 545min and 22 d. Overall, 33 patients (72%) did not require any additional interventional or surgical treatment. Thirty-day and 90-d mortality were 11% (5/46) and 15% (7/46). The 1-yr, 2-yr, and 3-yr cancer specific mortality (CSM)-free survival rates were 77%, 62%, and 56%, respectively. After stratification, according to metastatic status at diagnosis, CSM-free survival rates were significantly lower for cM1 patients compared with cM0 patients (1-yr 46% vs 93%, 2-yr 23% vs 81%, 3-yr 23% vs 73%, p<0.01). Our study is limited by its retrospective and uncomparative nature. CONCLUSIONS: RN with CT using ECC and DHCA is a challenging procedure which requires a dedicated multidisciplinary working team to minimise complications and maximise patients' outcomes. PATIENT SUMMARY: Patients with kidney cancer and a thrombus within the inferior vena cava, which reaches above the diaphragm, can be treated with surgery. However, this kind of surgical treatment is challenging and requires a dedicated multidisciplinary team in order to accomplish the task.

Time of onset of vardenafil orodispersible tablet in a real-life setting - looking beyond randomized clinical trials.

BACKGROUND: A rapid onset of action for phosphodiesterase type 5 inhibitors (PDE5is) emerged to be of clinical importance in men treated for erectile dysfunction (ED). Data from randomized clinical trials (RCTs) showed a rapid onset of action for vardenafil 10 mg orodispersible tablet (ODT). However, the effectiveness of vardenafil ODT has never been tested in a real-life setting. We assessed the efficacy and time to onset of action of vardenafil ODT in men seeking medical help for ED in the everyday real-life clinical practice. RESEARCH DESIGN AND METHODS: Patients completed a baseline and follow-up International Index of Erectile Function (IIEF), along with a 8-item self-administered questionnaire about onset of action and overall treatment outcomes. Descriptive statistics tested efficacy rates, patient timing of drug intake and time to post-dosing onset of action. RESULTS: Overall, 118(59.9%) patients used vardenafil ODT. Satisfactory erections for vaginal penetration were reported in 39(34.5%) and 26(21.8%), patients in =15 and =30, minutes post-dosing, respectively. Minimal Clinically Important Differences (MCIDs) criteria and Yang's criteria for responders were obtained in 80(67.8%) and 72(60.8%) patients. CONCLUSIONS: This study showed that one in three patients had satisfactory erection for vaginal penetration in less than 15 min post-dosing in the real-life setting.

Metabolic syndrome in White-European men presenting for secondary couple's infertility: an investigation of the clinical and reproductive burden.

We aimed to determine the impact of metabolic syndrome (MetS) on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorised 0 vs 1 vs 2 or higher). NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 (12%) of 167 men. Patients with MetS were older (P < 0.001) and had a greater BMI (P < 0.001) compared with those without MetS. MetS patients had lower levels of total testosterone (P = 0.001), sex hormone-binding globulin, inhibin B, and anti-Mόllerian hormone (all P ≤ 0.03), and they were hypogonadal at a higher prevalence (P = 0.01) than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology (all P ≤ 0.03). At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple's infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men.

Serenoa repens, selenium and lycopene to manage lower urinary tract symptoms suggestive for benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a disease affecting most of the elderly male. α1-blockers and 5-alpha reductase inhibitors are currently used to target lower urinary tract symptoms (LUTS). Moreover phytotherapeutic agents, including Serenoa Repens (SeR), have shown to have a role in ameliorating BPH/LUTS alone or in combination of other elements like Selenium (Se) and Lycopene (Ly). Areas covered: A literature review was performed using data from articles assessing the role of of SeR+Se+Ly in the management of LUTS secondary to BPH. Diverging evidence on SeR's efficacy is available. On one hand several studies have shown SeR efficacy in treating BPH/LUTS. SeR is effective in reducing prostate size, urinary frequency, dysuria, nocturia and in improving maximum urine flow-rate. On the other hand two long-term trials reported that SeR did not improve prostate size or urinary flow. SeR+Se+Ly in combination with tamsulosin is more effective than single therapies in improving IPSS and increasing maximal urinary flow-rate in patients affected by LUTS/BPH. Expert opinion: Despite great amount of preclinical and clinical studies, the use of SeR in BPH/LUTS is not sustained by clear evidence for a therapeutic efficacy but current data hint higher efficacy of of SeR+Se+Ly compared to SeR alone.

Avanafil - a further step to tailoring patient needs and expectations.

INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5Is) represent the first-line treatment for erectile dysfunction (ED). Almost one in two patients, however, show some level of treatment dissatisfaction and up to 30% fail to respond to any of the currently available PDE5Is. Recently, the second-generation PDE5I avanafil was launched for the treatment of ED. AREAS COVERED: Pivotal studies of clinical development along with placebo-controlled randomized clinical trials (RCTs) of avanafil in patients with ED were reviewed. Studies concerning the pharmacokinetics and pharmacodynamic of the drug were also analysed. A systematic literature search for English-language studies published up to May 2016 using the Medline database was performed. The search included the terms avanafil and ED. Expert commentary: Avanafil is a potent, highly selective PDE5I whose efficacy is comparable to that of currently available PDE5Is in both naïve and previous PDE5I users. Avanafil is effective within approximately 15 minutes of dosing, thus representing the only PDE5I approved for as-needed use, 15 to 30 minutes before sexual activity. Avanafil has high selectivity for the PDE5 isoenzyme, thus resulting in a lower incidence of drug-related side effects compared to other PDE5Is.

Preoperative Favorable Characteristics in Bladder Cancer Patients Cannot Substitute the Necessity of Extended Lymphadenectomy During Radical Cystectomy: A Sensitivity Curve Analysis.

OBJECTIVE: To investigate the staging of lymphadenectomy during radical cystectomy (RC) due to bladder cancer. No data exist about the possibility to limit the extension of pelvic lymph node dissection (PLND) on the basis of preoperative or intraoperative parameters without losing accuracy in the staging procedure. MATERIALS AND METHODS: Between 1995 and 2012, 1016 RC due to bladder cancer were performed at a single tertiary care institution. The relationship between the number of nodes removed and the probability to find node metastases at final pathology examination was assessed using receiver operating characteristic analyses. RESULTS: Among the patients who underwent RC plus PLND, the lymph node metastases prevalence was 35.7% (363 of 1016). Receiver operating characteristic curve analyses were used to explore graphically the relationship between the numbers of removed and examined nodes and the probability of finding one or more metastatic nodes in the overall population. The curve indicated that 25, 35, and 45 nodes need to be removed to achieve 75%, 90%, and 95% probability, respectively, of detecting one or more lymph node metastases. When the analyses were stratified according to preoperative characteristics, only slight differences were recorded among the sensitivity analyses stratified for pathological stage, primary or progressive status, or radiological N status. CONCLUSION: Our results show that it is necessary to extend PLND to improve the ability to stage node metastases accurately. Preoperative parameters can minimally change this indication and an extended PLND should be always performed.

Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats.

AIMS: To test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. METHODS: Male rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3 mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5 µg rimonabant (CB1 antagonist) or 5 µg SR144528 (CB2 antagonist) were studied in awake rats. RESULTS: After administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH. CONCLUSIONS: Urodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. © 2015 Wiley Periodicals, Inc.

Long-term recovery of normal sexual function in testicular cancer survivors.

Testicular cancer (TC) is the most common solid cancer in men between the third and fourth decade of life. Due to successful treatment approaches, TC survivors (TCSs) have long life expectancy, but with numerous potential long-term sequelae, including sexual dysfunction. We investigated predictors of long-term normal sexual function (SF) recovery in TCSs. Sociodemographic, medical, and psychometric data were analyzed in 143 Caucasian-European TCSs, who underwent orchiectomy at a single institution. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF). Statistical models tested the association between predictors (including age at surgery, body mass index, CCI, and adjuvant therapy: radiotherapy [RT], chemotherapy [CT], CT followed by retroperitoneal lymph node dissection [RPLND] and RPLND alone) and the long-term recovery of normal SF (defined as IIEF-erectile function [EF] ≥26, and sexual desire [SD], intercourse satisfaction [IS] orgasmic function [OF], and overall satisfaction [OS] domain scores in the upper tertiles). At a mean follow-up of 86 months, 35 (25.5%) TCSs had erectile dysfunction (ED), with 16 (11.2%) experiencing severe ED. Median time of EF recovery was 60, 60, and 70 months after CT, RT, and RPLND, respectively. Only adjuvant RT emerged as an independent predictor of nonrecovery of normal EF (HR: 0.55, P= 0.01). Neither adjuvant CT nor CT plus RPLND or RPLND alone significantly impaired the recovery of normal erections. Adjuvant therapy was not associated with impaired recovery of normal sexuality as a whole, considering the IIEF-SD, -OF, -IS, and OS domains.

Follow-up After Treatment for Renal Cell Carcinoma: The Evidence Beyond the Guidelines.

CONTEXT: Postoperative follow-up is considered the standard of care for nonmetastatic renal cell carcinoma (RCC). However, level 1 evidence regarding a proper follow-up protocol for RCC is still lacking, making clinical practice extremely heterogeneous. OBJECTIVE: To evaluate systematically and summarise the evidence supporting the current clinical guidelines on follow-up after RCC treatment. EVIDENCE ACQUISITION: A search of Medline, PubMed and Scopus was performed to identify articles published in the last 5 yr addressing the role of follow-up in the RCC setting. Relevant studies were then screened, and the data were extracted, analysed, and summarised. The Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria were applied. EVIDENCE SYNTHESIS: Although several series regarding oncologic outcomes and protocols of surveillance after nephrectomy for localised RCC have been published in the literature, the individual preferences of the treating urologist make the daily clinical scenario extremely heterogeneous regarding follow-up indications and modality. Clinical guidelines support a stage-specific stratification of patient prognosis based on pathologic staging or prognostic models. In the context of a prospectively durable follow-up protocol exposing patients to several imaging tests, concerns about radiation exposure must be taken into account. A better understanding of tumour biology, which would lead to a correct individualisation of patient prognosis through the use of validated prognostic tools, would allow for a more tailored follow-up treatment. CONCLUSIONS: A consensus regarding the pattern and modalities of surveillance after treatment for RCC is still lacking. A standardised evidence-based surveillance protocol that would allow for the early detection of recurrences and limit unnecessary radiation exposure and unwarranted costs is mandatory. PATIENT SUMMARY: A surveillance protocol after treatment for a renal tumour is essential for the early detection and treatment of eventual metastases. A general consensus regarding timing and modalities for follow-up protocol still does not exist, but published evidence commonly sustains some general principles.

Peyronie's disease and autoimmunity­a real-life clinical study and comprehensive review.

INTRODUCTION: Although heavily investigated over the last decades, Peyronie's disease (PD) pathogenesis remains unclear. AIM: We sought to investigate the association between PD and autoimmune diseases (ADs) in men seeking medical help for sexual dysfunction in the real-life setting. METHODS: Complete sociodemographic and clinical data from a homogenous cohort of 1,140 consecutive Caucasian-European men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index and ADs were stratified according to International Classification of Diseases, Ninth Revision classification. MAIN OUTCOME MEASURES: Descriptive statistics and multivariate logistic regression models tested the association between ADs and PD. RESULTS: PD was diagnosed in 148 (13%) of the 1,140 men; of PD patients, 14 (9.5%) had a comorbid AD; conversely, the rate of ADs in non-PD patients was significantly lower (χ(2) = 24.7; P < 0.01). Both patient age and AD comorbidity achieved multivariable independent predictor status for PD (odds ratio [OR]: 1.05; P < 0.01 and OR: 4.90; P < 0.01, respectively). CONCLUSIONS: Our observational findings showed that ADs are highly comorbid with PD in a large cohort of same-race individuals seeking medical help for sexual dysfunction in the real-life setting.