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

Summary 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

Words of Wisdom RE: Low adherence to guidelines in nonmuscle-invasive disease

Non peer reviewedPostprin

Effect of allogeneic intraoperative blood transfusion on survival in patients treated with radical cystectomy for nonmetastatic bladder cancer: Results from a single high-volume institution

Transfusion has been related to poor survival after surgery in several cancers. Recently, timing of transfusion has been proposed as crucial in the determination of poor survival expectanies after surgery, in fact, intra- operative but not postoperative transfusion were found to be related. We confirmed these findings in patients who underwent radical cystectomy because of bladder cancer; physicians should avoid use of transfusion intraoperatively. Background: Previous studies have demonstrated that perioperative blood transfusion (BT) is associated with a significantly increased risk of cancer recurrence and mortality after radical cystectomy (RC). Recently, it was shown for the first time that intraoperative transfusion has a detrimental effect on cancer survival. The aim of the current study was to validate this finding in a single European institution. Patients and Methods: The study focused on 1490 consecutive nonmetastatic bladder cancer patients treated with RC at a single tertiary care referral center between January 1990 and August 2013. KaplaneMeier analyses and Cox regression analyses were used to assess the effect of timing of BT administration (no transfusion vs. intraoperative transfusion vs. postoperative transfusion vs. intra- operative and postoperative transfusion) on cancer-specific mortality (CSM), overall mortality (OM), and disease recurrence. Results: Mean age at the time of RC was 67 years. Overall, 322 (21.6%) patients received intraoperative BT and 97 (6.5%) received postoperative BT. At a mean follow-up time of 125 months (median, 110 months), the 5- and 10-year CSM rate was 846 (58%) and 715 (48%), respectively. In multivariable analyses patients who received intraoperative BT had greater risk of disease recurrence (hazard ratio [HR], 1.24; P .2). Conclusion: Our study confirms that intraoperative, but not postoperative BT, are related to a detrimental effect on survival after RC. These results should be take into account by physicians to administer BT using the correct timing

Sense and Nonsense of an Extended Pelvic Lymph Node Dissection in Prostate Cancer

Lymph node metastases associated with prostate cancer (PCa) has been shown to be a poor prognostic factor. The role of pelvic lymph node dissection (PLND) itself in relation to survival remains unclear, however. A Medline search was conducted to address this issue. The following conclusions were drawn. Only recently, improved survival due to completion of radical prostatectomy (RP) (compared to abandoning RP) in known or presumed lymph-node-positive patients has been shown. Lymph node sampling can only be considered representative if an adequate number of nodes is removed. While several authors have suggested that a therapeutic benefit in patients undergoing RP is not provided by PLND, the reliability of these studies is uncertain. Contrary to this, several studies have indicated the possibility of long-term survival even in the presence of limited lymph node metastases. The role and timing of initiation of adjuvant androgen deprivation therapy (ADT) in patients who have node-positive disease after RP is controversial. Recent studies suggest that delaying ADT may not adversely impact survival

Cittadinanza attiva e Costituzione

Il percorso formativo si propone di fornire le conoscenze basilari del Diritto costituzionale in una prospettiva di maturazione negli studenti dei fondamenti culturali della cittadinanza attiva, che rappresenta una condizione indispensabile nel processo di sviluppo della persona e nell’ambito delle relazioni sociali, con particolare riguardo a quelle che interessano il contesto del lavoro. Il programma si articolerà in un primo incontro con il coordinatore scientifico Prof. Alberto Lucarelli di impostazione seminariale, in occasione del quale verranno illustrati i principi fondativi del modello di Stato democratico rappresentativo che sono sanciti nella nostra Carta costituzionale. A seguire, verranno realizzati dei moduli laboratoriali su specifici temi che verranno trattati sulla base di un più diretto coinvolgimento degli studenti, attraverso ad esempio simulazioni, realizzazione di mappe concettuali, etc

Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial

Objectives To determine the efficacy of intraoperative treatment with low dose tranexamic acid in reducing the rate of perioperative transfusions in patients undergoing radical retropubic prostatectomy

Does prostate acinar adenocarcinoma with Gleason Score 3 + 3 = 6 have the potential to metastasize?

Background: There is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer. Case description: We report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3 + 3 = 6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (<5% of the whole tumor) of Gleason pattern 4 (poorly formed glands) was found in an extraprostatic position. Conclusion: The epilogue was that the additional finding changed the final Gleason score to 3 + 3 = 6 with tertiary pattern 4 and the stage to pT3a. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/13000_2014_19

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

Can Bayesian Network empower propensity score estimation from Real World Data?

A new method, based on Bayesian Networks, to estimate propensity scores is proposed with the purpose to draw causal inference from real world data on the average treatment effect in case of a binary outcome and discrete covariates. The proposed method ensures maximum likelihood properties to the estimated propensity score, i.e. asymptotic efficiency, thus outperforming other available approach. Two point estimators via inverse probability weighting are then proposed, and their main distributional properties are derived for constructing confidence interval and for testing the hypotheses of absence of the treatment effect. Empirical evidence of the substantial improvements offered by the proposed methodology versus standard logistic modelling of propensity score is provided in simulation settings that mimic the characteristics of a real dataset of prostate cancer patients from Milan San Raffaele Hospital

Elective nodal radiotherapy in prostate cancer

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy