The impact of mpMRI-targeted vs systematic biopsy on the risk of prostate cancer downgrading at final pathology.

PURPOSE: Although targeted biopsies (TBx) are associated with improved disease assessment, concerns have been raised regarding the risk of prostate cancer (PCa) overgrading due to more accurate biopsy core deployment in the index lesion. METHODS: We identified 1672 patients treated with radical prostatectomy (RP) with a positive mpMRI and ISUP ≥ 2 PCa detected via systematic biopsy (SBx) plus TBx. We compared downgrading rates at RP (ISUP 4-5, 3, and 2 at biopsy, to a lower ISUP) for PCa detected via SBx only (group 1), via TBx only (group 2), and eventually for PCa detected with the same ISUP 2-5 at both SBx and TBx (group 3), using multivariable logistic regression models (MVA). RESULTS: Overall, 12 vs 14 vs 6% (n = 176 vs 227 vs 96) downgrading rates were recorded in group 1 vs group 2 vs group 3, respectively (p < 0.001). At MVA, group 2 was more likely to be downgraded (OR 1.26, p = 0.04), as compared to group 1. Conversely, group 3 was less likely to be downgraded at RP (OR 0.42, p < 0.001). CONCLUSIONS: Downgrading rates are highest when PCa is present in TBx only and, especially when the highest grade PCa is diagnosed by TBx cores only. Conversely, downgrading rates are lowest when PCa is identified with the same ISUP through both SBx and TBx. The presence of clinically significant disease at SBx + TBx may indicate a more reliable assessment of the disease at the time of biopsy potentially reducing the risk of downgrading at final pathology.

Ultrafast photochemistry and electron-diffraction spectra in n → (3s) Rydberg excited cyclobutanone resolved at the multireference perturbative level.

We study the ultrafast time evolution of cyclobutanone excited to the singlet n → Rydberg state through non-adiabatic surface-hopping simulationsperformed at extended multi-state complete active space second-order perturbation (XMS-CASPT2) level of theory. These dynamics predict relaxation to the ground-state with a timescale of 822 ± 45 fs with minimal involvement of the triplets. The major relaxation path to the ground-state involves a three-state degeneracy region and leads to a variety of fragmented photoproducts. We simulate the resulting time-resolved electron-diffraction spectra, which track the relaxation of the excited state and the formation of various photoproducts in the ground state.

Electron and ion spectroscopy of azobenzene in the valence and core shells.

Azobenzene is a prototype and a building block of a class of molecules of extreme technological interest as molecular photo-switches. We present a joint experimental and theoretical study of its response to irradiation with light across the UV to x-ray spectrum. The study of valence and inner shell photo-ionization and excitation processes combined with measurement of valence photoelectron-photoion coincidence and mass spectra across the core thresholds provides a detailed insight into the site- and state-selected photo-induced processes. Photo-ionization and excitation measurements are interpreted via the multi-configurational restricted active space self-consistent field method corrected by second order perturbation theory. Using static modeling, we demonstrate that the carbon and nitrogen K edges of azobenzene are suitable candidates for exploring its photoinduced dynamics thanks to the transient signals appearing in background-free regions of the NEXAFS and XPS.

Contemporary role of palliative cystoprostatectomy or pelvic exenteration in advanced symptomatic prostate cancer.

OBJECTIVE: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). PATIENTS AND METHODS: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien-Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. RESULTS: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15 months (range 3-41) for the entire cohort with a median survival of 15 months (95% CI 10.1-19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62-17.23, p = 0.164). CONCLUSION: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.

Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study.

BACKGROUND: Pembrolizumab is a new standard of care for patients with platinum-treated, metastatic urothelial carcinoma (UC). Nab-paclitaxel is active in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC. PATIENTS AND METHODS: PEANUT was an open-label, single-arm, phase II trial that included patients who had failed one or two chemotherapy regimens, including platinum chemotherapy. Biomarker analyses focused on programmed cell-death ligand-1 combined positive score (CPS) and comprehensive genomic profiling on tumor samples and circulating tumor DNA. Patients received 200 mg pembrolizumab on day 1 (D1), and 125 mg/m2 nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) according to RECIST (v1.1). The assumption was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). RESULTS: Between January 2019 and January 2020, the PEANUT study enrolled 70 patients: 24% had failed two prior systemic therapies; 31% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1; and 28.6% had liver metastases. After a median follow-up of 9.8 months, 40 patients have relapsed (57.1%). The median PFS was 5.9 months [95% confidence interval (CI) 3.1-11.5]. The confirmed objective response rate (ORR) was 38.6% (95% CI 27-51) with 17 partial responses and 10 complete responses (14.3%). The median duration of response was not reached. Five patients (7.1%) had ongoing responses lasting >12 months. The most common any-grade treatment-related adverse events included alopecia (71.4%), neutropenia (32.9%), and peripheral neuropathy (34.3%). Neither tumor mutational burden nor CPS was significantly associated with PFS at univariable analyses. The single-arm design of the trial was the major limitation. CONCLUSIONS: Pembrolizumab combined with nab-paclitaxel, as second- and third-line chemoimmunotherapy for metastatic UC, showed a favorable safety profile, durable PFS, and a clinically meaningful ORR in these preliminary analyses. This combination warrants additional randomized studies in earlier disease stages. CLINICALTRIALS. GOV NUMBER: ClinicalTrials.govNCT03464734; https://clinicaltrials.gov/ct2/show/NCT03464734.

Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study☆.

BACKGROUND: Initial studies of preoperative checkpoint inhibition before radical cystectomy (RC) have shown promising pathologic complete responses. We aimed to analyze the survival outcomes of patients enrolled in the PURE-01 study (NCT02736266). PATIENTS AND METHODS: We report the results of the secondary end points of PURE-01 in the final population of 143 patients. In particular, we report the event-free survival (EFS) outcomes, defined as the time from the first cycle of pembrolizumab to radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy (NAC), recurrence after RC, or death from any cause. Other end points were recurrence-free survival (RFS) and overall survival (OS). Subgroup analyses were carried out, including pathological response category, clinical complete responses (CR) assessed via multiparametric magnetic resonance imaging (mpMRI), and molecular subtyping. Cox regression analyses for EFS were also carried out. RESULTS: After a median [interquartile range (IQR)] follow-up of 23 (15-29) months, 12- and 24-month EFS were 84.5% [95% confidence interval (CI): 78.5-90.9] and 71.7% (62.7-82). The prognosis was favorable across all the different pathological response subgroups, with the exception of ypN+ (N = 21), showing a 24-month RFS (95% CI) of 39.3% (19.2% to 80.5%). A statistically significant EFS benefit was observed in patients with a clinical CR (P = 0.002). Programmed cell-death-ligand-1 combined positive score was significantly associated with longer EFS in multivariable analyses. Four patients refused RC after clinical evidence of CR, and none of them have recurred after a median follow-up of 10 months (IQR: 11-15). The claudin-low subtype displayed a numerically longer EFS after pembrolizumab and RC compared with the other subtypes. CONCLUSIONS: The EFS results from PURE-01 revealed that the immunotherapy effect was maintained post-RC in most patients. Pembrolizumab compared favorably with neoadjuvant chemotherapy, irrespective of the biomarker status. Molecular subtyping may be a useful tool to select the patients who are predicted to benefit the most from neoadjuvant pembrolizumab.

MpMRI of the prostate: is there a role for semi-quantitative analysis of DCE-MRI and late gadolinium enhancement in the characterisation of prostate cancer?

AIM: To assess whether there is a significant difference in perfusion parameters between benign and malignant prostatic lesions, focusing on semi-quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and presence of late gadolinium enhancement (LGE). MATERIAL AND METHODS: Three hundred and thirteen patients who underwent multiparametric MRI (mpMRI) of the prostate and with available corresponding histology (prostatectomy or biopsy) were selected retrospectively for this study. The MRI protocol consisted of multiplanar T2-and diffusion-weighted imaging, DCE and delayed axial T1 images. Images were reviewed independently by two radiologists for LGE assessment and Prostate Imaging - Reporting and Data System (PI-RADS) scoring. For each lesion, semi-quantitative analysis of DCE-MRI was performed and the following data were evaluated: time to peak, wash-in rate, wash-out rate, brevity of enhancement, and area under the curve. The presence or absence of LGE in delayed axial T1 images was assessed qualitatively. MRI results were compared to histology. The presence of significant prostate cancer was based both on Epstein criteria (SPC) and Gleason score (GS ≥7). RESULTS: SPC and Gleason score ≥7 tumours showed significant lower time to peak and brevity of enhancement (p<0.001) with higher wash-in rate (p=0.001). LGE was observed in 152/313 (49%) cases; among them 103/152 (68%) did not show SPC whereas 49/152 (32%) had SPC (p<0.001). The presence of LGE determined a risk reduction of SPC resulting as an independent predictor at multivariate analysis (logOR=-0.78, SE 0.33, p=0.02). CONCLUSION: Semi-quantitative perfusion analysis and LGE may help to predict the presence/absence of a significant prostate tumour and represent a promising tool to improve mpMRI diagnostic performance.

Efficacy and safety of dapoxetine in treatment of premature ejaculation: an evidence-based review.

BACKGROUND: Premature ejaculation (PE) is a major issue in male sexual health, with a global prevalence estimated to be between 20% and 40%, making it the most common sexual dysfunction in men. PE causes distress and reduced quality of life for patients and has a negative impact on interpersonal relationships. Historically, it has been treated with cognitive therapy, behavioural methods and off-label use of selective serotonin reuptake inhibitors (SSRIs) usually used to treat depression and other psychological disorders. Dapoxetine is the only SSRI specifically designed to treat PE. MECHANISM OF ACTION: Dapoxetine hydrochloride is a potent inhibitor of serotonin reuptake transporters. Dapoxetine is suited for 'on-demand' treatment of PE because of its rapid absorption and short initial half-life. EFFICACY: Evidence from published studies showed that dapoxetine 30 mg or 60 mg taken 'on-demand' results in a significant increase in intravaginal ejaculatory latency time (IELT) when compared with placebo. Most patient-reported outcomes are clearly improved relative to placebo following dapoxetine therapy, indicating greater control over ejaculation, more satisfaction with intercourse, less ejaculation-related distress and significantly reduced interpersonal difficulties. SAFETY: The most common adverse events with dapoxetine are nausea, dizziness, somnolence, headache, diarrhoea and insomnia. Usually they do not lead to drug discontinuation. CONCLUSION: Dapoxetine is the only effective and safe available on-label oral treatment for PE, and its use can result in better quality of life for the patient and their sexual partner.

Imaging biomarkers in prostate cancer: role of PET/CT and MRI.

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed.

Fifteen-year single-centre experience with three different surgical procedures of nerve-sparing cystectomy in selected organ-confined bladder cancer patients.

OBJECTIVES: To evaluate technical feasibility and oncologic and functional outcomes of three different surgical procedures of nerve-sparing radical cystectomy (NS-RC) for the treatment of organ-confined bladder cancer at a single referral centre. MATERIALS AND METHODS: All consecutive cases of NS-RC carried out between 1997 and 2012 were retrospectively analysed. NS-RC included nerve-sparing cysto-vesicleprostatectomy (NS-CVP), capsule-sparing cystectomy (CS-C) and seminal-sparing cysto-prostatectomy (SS-CP). Peri-operative parameters and post-operative outcomes were analysed. RESULTS: Overall, 90 patients underwent NS-RC, 35 (38.9 %) of whom received a NS-CVP, while 36 (40 %) and 19 (21.1 %) underwent capsule CS-C and SS-CP, respectively. No difference was registered comparing oncologic outcomes of the three different techniques; however, two local recurrences after CS-C were attributed to the surgical technique. Complete post-operative daytime and night-time urinary continence (UC) at 24 and 48 months was achieved in 94.4 and 74.4 % and in 88.8 and 84.4 % of cases, respectively. CS-C showed both the best UC and sexual function preservation rate at early follow-up (24 months). Overall, a satisfactory post-operative erectile function (IIEF-5 ≥ 22) was proved in 57 (68.6 %) and 54 (65.0 %) patients at 24 and 48 months, respectively. Significant difference was found when comparing sexual function preservation rate of NS-CVP (28.5 %) to that of CS-C (91.6 %) and SS-CP (84.2 %). CONCLUSION: NS-RC for male patients accounted for 7.4 % of overall radical cystectomy. To a limited extent of the selected organ-confined bladder cancers treated, the three different procedures analysed showed comparable results in terms of local recurrence and cancer-specific survival. Both CS-C and SS-CP procedures provided excellent functional outcomes when compared to original NS-CVP.

Pelvic nerve injury negatively impacts female genital blood flow and induces vaginal fibrosis-implications for human nerve-sparing radical hysterectomy.

OBJECTIVE: This study sought to develop a novel animal model to study the impact of nerve-sparing radical hysterectomy (NSRH) on female genital blood flow. DESIGN: In vivo animal study. POPULATION: Thirty Sprague-Dawley female rats. MATERIALS AND METHODS: Female rats underwent either unilateral pelvic nerve (PN) crush (PNC; n = 9), or crush of both the PNs and all efferent nerves in the pelvic plexus ('clock-nerve crush', CNC; n = 9). Under anaesthesia, we electrically stimulated the crushed PN at 3 and 10 days after crush while monitoring blood pressure and recording clitoral and vaginal blood flows by laser Doppler. Uninjured PNs were stimulated as an internal control. Twelve additional rats were assigned either to bilateral PNC or sham surgery, and genital tissues were processed 10 days after injury for in vitro analysis. MAIN OUTCOME MEASURES: Genital blood flow, nNOS, eNOS, collagen I-III. RESULTS: Stimulation of the crushed PN in both groups subjected to PNC and CNC induced significantly lower peak genital blood flow at 3 and 10 days (P < 0.05) compared to stimulation of the non-crushed control PN. The immunofluorescence and Western blot analyses revealed that all injured rats exhibited more vaginal collagen III and collagen I than rats did that ad undergone sham surgeries (P < 0.05). PCN reduced nNOS expression in both clitoral and vaginal tissue. CONCLUSIONS: Based on our study it may be hypothesised that NSRH might cause reductions of genital blood flow and vaginal fibrosis due to neurapraxia of the pelvic nerve and reductions of nNOS nerve fibres in clitoral and distal vaginal tissue. TWEETABLE ABSTRACT: Pelvic nerve neurapraxia during nerve-sparing radical hysterectomy could lead to sexual arousal dysfunction.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment.

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

Intensity-modulated radiation therapy leads to survival benefit only in patients with high-risk prostate cancer: a population-based study.

BACKGROUND: During the last years, there has been a rapid adoption of intensity-modulated radiation therapy (IMRT) in patients with prostate cancer (PCa), despite the lack of randomized trials evaluating its effectiveness. The aim of our study was to evaluate the survival benefit associated with IMRT in patients with PCa. PATIENTS AND METHODS: Overall, 42 483 patients with PCa treated with IMRT or initial observation between 2001 and 2007 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare were evaluated. Patients in both treatment arms were matched using propensity-score methodology. After propensity-score matching, 19 064 patients remained in our analyses. Eight-year cancer-specific mortality (CSM) rates were estimated, and the number needed to treat (NNT) was calculated. Competing risks regression analyses tested the relationship between treatment type and CSM. RESULTS: Overall, the 8-year CSM rates were 3.4% and 4.1% for patients treated with IMRT versus initial observation, respectively (P < 0.001). The corresponding 8-year NNT was 142. In patients with low/intermediate-risk disease, IMRT was not associated with lower CSM rates compared with observation (P = 0.7). In patients with high-risk disease, the 8-year CSM rates for IMRT versus observation were 5.8% versus 10.5%, respectively (P < 0.001). The corresponding NNT was 21. When high-risk patients were stratified according to age (<73 versus ≥73), and Charlson comorbidity index (≤1 versus >1) the 8-year CSM rates for IMRT versus observation were 4.3% versus 9.4% and 6.9% versus 11.9% and 5.3% versus 11.4% and 6.1% versus 10.1%, respectively (all Ps < 0.001). The corresponding NNTs were 19, 21, 16, and 25, respectively. In multivariate analyses, the protective effect of IMRT was more evident in high-risk patients with younger age and lower comorbidities. CONCLUSIONS: IMRT leads to a survival advantage only in patients with high-risk disease. Conversely, patients with low/intermediate-risk disease did not benefit from IMRT at 8-year follow-up.

Effects of Difaprost® on voiding dysfunction, histology and inflammation markers in patients with benign prostatic hyperplasia who are candidates for surgical treatment.

AIM: Although previous studies assessed the effects of Serenoa repens, quercetin and ß-sitosterol on inflammatory parameters, no randomized studies have tested the combination of these agents neither on BPH symptoms nor on the inflammatory pattern. The aim of this trial was to evaluate the effects of Difaprost® on voiding dysfunction, histological inflammatory alterations and apoptotic molecular mechanisms in BPH patients. METHODS: We included 36 patients affected by BPH with obstructive symptoms eligible for surgery. Patients were randomly assigned to two groups: 18 patients received Difaprost® for three months before surgery, and 18 patients did not receive any additional therapy and were scheduled for surgery. All patients receiving Difaprost® were evaluated with uroflowmetry with post-void residual volume (PVR) evaluation, serum PSA, and IPSS questionnaire before and after treatment. Moreover, we evaluated inflammatory patterns in prostatic specimens at final pathology. RESULTS: Even without statistically significant differences on inflammatory pattern between patients receiving Difaprost® and controls, patients receiving Difaprost® had lower presence of edema and angiectasia at histological evaluation of prostate specimens. Moreover, patients included in the treatment group had a clinically significant reduction of PVR (46.1 vs. 25.2 mL; P=0.1) and a slight increase in Qmed (5.6 vs. 6.5 mL/s; P=0.9) after three months of chronic treatment with Difaprost®. No statistically significant differences were recorded in other clinical parameters between patients receiving Difaprost® and controls. CONCLUSION: Although not statistically significant, patients treated with Difaprost® showed an improvement in voiding function compared to controls (namely, an increase in Qmed and a reduction of PVR). Future trials with a larger number of patients and a longer treatment period could be necessary to evaluate the clinical efficacy of Difaprost®.

Extended pelvic lymph node dissection in prostate cancer: a 20-year audit in a single center.

BACKGROUND: We set to assess the impact of stage migration in prostate cancer (PCa) on the evolution of the pN1 rate and tumor characteristics in pN1 patients over the last two decades. PATIENTS AND METHODS: We evaluated 5274 PCa patients treated with radical prostatectomy and anatomically extended pelvic lymph node dissection (ePLND) between 1990 and 2010. Year-per-year trends of clinical and pathological characteristics were examined. Logistic regression analyses addressed predictors of pN1. RESULTS: The median number of lymph nodes (LNs) removed was 16.0. Overall, the pN1 rate was 13.8% and it decreased from 26.1% to 15.6% between 1990 and 2010 (P < 0.001). For the same period, the pN1 rate changed from 0% to 3% in the low-risk PCa, from 20% to 7% in the intermediate-risk PCa, and from 33% to 44% in the high-risk PCa (P ≤ 0.01). In pN1 patients, pre-operative cancer characteristics and the median number of positive LNs (three in 1990 versus two in 2010) did not significantly change overtime (all P ≥ 0.1). Year of surgery was not an independent predictor of pN1 (all P ≥ 0.06). CONCLUSION: Based on ePLND outcomes, contemporary patients with intermediate- and high-risk PCa's still harbor a significant LNI risk. In consequence, stage migration does not justify omitting or limiting the extent of PLND in these individuals.

Diagnosis of BPH and treatment of LUTS among GPs: a European survey.

AIMS OF THE STUDY: This survey was conducted in France, Germany, Italy, Spain and UK, with the aim to assess diagnosis and therapy of BPH patients in clinical practice. METHODS USED TO CONDUCT THE STUDY: A selected cohort of 455 general practitioners (GPs) in Europe were asked to report information on BPH patients with lower urinary tract symptoms (LUTS), including patient characteristics, diagnostic procedures, severity of illness, symptoms duration and underlying conditions. The GPs provided data relating to 886 patients. RESULTS OF THE STUDY: The diagnostic work-up included description of symptoms (74.9-85.1%), rectal examination (55.4-82.1%) and the determination of PSA (79.1-94.7%). Transrectal sonography was popular in Italy and France (51.1% and 55.9%, respectively), less so in Germany (15.3%) and Spain (13.1%) and not at all in the UK (2.3%). At diagnosis, the most common symptom was nocturia (71-88%), followed by frequency (15-79%), urgency (43-68%) and weak stream (47-64%). The most common combination was the triad nocturia-frequency-feeling of incomplete emptying (22-31%). The mean ± SD LUTS severity score was similar in all countries: The main aim of treatment was the resolution of nocturia, which had an average score that reflected an important need (> 3.5) closely followed by frequency (3.3-3.9). CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: This survey has shown that the most common LUTS is nocturia. Analyses of the symptoms' pattern revealed that the most common combination appears to be the triad nocturia-frequency-feeling of incomplete emptying. An association between LUTS and heart disease, diabetes and hypertension suggests that the pharmacological treatment should be devoid of effects on the cardiovascular system. With alpha blockers as first line treatment of LUTS, respondents were more concerned with hypotensive episodes resulting in falls, rather than about other typical side effects (e.g. ejaculation disorders and lowered libido). The survey highlights educational needs in diagnostics.

Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates.

BACKGROUND: As the clinical effects of the available α1-adrenoceptors (ARs) blockers are usually considered comparable for treatment in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic enlargement, officially recognised guidelines do not make specific recommendations regarding the choice of which agent should be considered according to the patient's characteristics. AIM: To analyse data supporting the use of silodosin, a highly selective once-daily dosing α1-ARs blocker, in different daily clinical practice scenarios. MATERIALS AND METHODS: A structured literature review was performed using data retrieved from articles assessing the role of silodosin in the management of LUTS secondary to benign prostatic hyperplasia (BPH). A literature search of English language publications was performed using MEDLINE(®) and Web of Science from 2000 to 2012 using the terms LUTS; BPH; silodosin; α1-ARs blockers. The papers with the highest level of evidence were identified and represent the basis of the present review. RESULTS: Available data coming from basic research analyses, randomised trials and prospective studies showed that silodosin is efficacious for the initial management of patients with LUTS. Clinical developmental safety data from patients receiving silodosin with concomitant antihypertensive therapy do not indicate an increase in risk of orthostatic hypotension. In this context, a recent study demonstrated that silodosin can be safely administered to patients who are consensually assuming phosphodiesterase type 5 inhibitors. A recent randomised crossover study comparing the efficacy of silodosin and tamsulosin in patients with LUTS showed that further significant improvement was observed after switching to silodosin treatment, while worsening or little improvement was observed after switching to tamsulosin treatment. Preliminary results seem to demonstrate a potential role of silodosin in the treatment of chronic prostatitis/chronic pelvic pain syndrome and to facilitate ureteral stone passage, as well. DISCUSSION: When considering the above cited pharmacological and clinical characteristics of the drug, silodosin can be considered in the following clinical scenario: patients suffering from moderate-severe nocturia, patients with low normal blood pressure levels and patients concomitantly treated with antihypertensive medications, patients concomitantly treated with phosphodiesterase type 5 inhibitors, patients not satisfied (for efficacy or tolerability) with previous treatment with other α1-ARs blockers. CONCLUSION: Silodosin is efficacious for the initial management of patients with LUTS. Silodosin has a good cardiovascular safety profile and can be considered an option in patients with cardiovascular co-morbidities. It seems to be especially beneficial in patients with nocturia alone or presenting with the symptomatic trial nocturia-frequency-incomplete emptying. Patients on phosphodiesterase type 5 inhibitors treatment can be safely managed with silodosin.

Distribution of metastatic sites in renal cell carcinoma: a population-based analysis.

BACKGROUND: We assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases. PATIENTS AND METHODS: Patients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998-2007). Age was stratified into four groups: <55, 55-64, 65-74 and ≥ 75 years. Cochran-Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of multiple metastatic sites. Finally, we examined the rates of brain or bone metastases according to the presence of other metastatic sites. RESULTS: In 11,157 mRCC patients, the rate of multiple metastatic sites decreased with increasing age (P < 0.001). This phenomenon was confirmed in patients with lung, bone, liver and brain metastases (all P ≤ 0.01). The rate of bone metastases was 10% in patients with exclusive abdominal metastases and 49% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 2% in patients with exclusive abdominal metastases and 16% in patients with thoracic and bone metastases. CONCLUSIONS: The proportion of patients with multiple metastatic sites is higher in young patients. The rates of bone (10%-49%) and brain (2%-16%) metastases are nonnegligible in mRCC patients.