Therapeutic Advances in Urology

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  • ISSN
    1756-2880

Publications in this journal

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    ABSTRACT: Prostate cancer is the second leading cause of cancer death in men and there is an urgent clinical need to improve its detection and treatment. The introduction of prostate-specific antigen (PSA) as a biomarker for prostate cancer several decades ago represented an important step forward in our ability to diagnose this disease and offers the potential for earlier and more effective treatment. PSA measurements are now routinely conducted alongside digital rectal examination, with raised PSA levels leading to biopsy. PSA is also used to monitor disease and assess therapeutic response. However, there are some important limitations to its use, not least its lack of specificity for prostate cancer, and increased PSA screening may have resulted in overdiagnosis and overtreatment of early, low-risk prostate cancer. Therefore, there is a need for more specific and sensitive biomarkers for the diagnosis and monitoring of prostate cancer and treatment response; in particular, biomarkers of response to hormonal treatments in prostate cancer and predictive biomarkers to identify who is most likely to respond to these treatments. Here we review the current utilization of PSA and data on potentially more specific and sensitive biomarkers for the diagnosis and monitoring of prostate cancer: prostate cancer antigen 3 (PCA3) and the TMPRSS2-ERG fusion gene. A description of the design of an ongoing study of the 6-month extended release formulation of leuprorelin acetate (Eligard(®) 45 mg) will provide preliminary data on the potential utility of these new biomarkers for detecting therapeutic response after hormonal therapy.
    Therapeutic Advances in Urology 12/2014; 6(6):245-252.
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    ABSTRACT: To define the profile of patients with prostate cancer (PCa) receiving a 3-month or 6-month formulation of luteinizing hormone-releasing hormone (LHRH) agonist in France and the reasons for choosing between formulations. This prospective 1-year observational study included patients with PCa starting LHRH agonist therapy in everyday practice. Reasons for prescription and patient preference were recorded at inclusion, 3 or 6 months, and 12 months. The percentage of patients with a renewed initial prescription was recorded during follow up. A total of 1438 patients with PCa were included. Hormonotherapy was initiated more frequently with a 6-month (n = 903; 62.8%) than with a 3-month formulation (n = 535; 37.2%). The initial prescription was renewed in most patients after 3 or 6 months (86.1%) and 12 months (71%); 170 patients switched from a 3-month to a 6-month formulation during follow up. Presence of metastases influenced initial prescription (odds ratio 0.439; 95% confidence interval 1.095-1.892), with a 3-month formulation more often prescribed than a 6-month formulation to men with metastatic PCa at diagnosis (21.3% versus 15.8%, respectively). The most frequent reasons given by physicians for choosing the 6-month formulation were 'simplification of therapeutic regimen' (86.9%) or 'fewer unnecessary visits' (46.8%). Similar reasons were given for switching from a 3-month to a 6-month formulation during follow up. The most frequent reasons given by physicians to initiate therapy with a 3-month formulation were 'usual practice/habit' (55.5%) or 'closer patient management' (46.2%). 'Closer patient management' and 'reassuring effect upon patient' were the main reasons for switching from a 6-month to a 3-month formulation during follow up. Approximately 80% of patients were satisfied with the formulation they were prescribed and patients' reasons for preferring one formulation over another were similar to the physicians' reasons for prescribing these formulations. Slow-release formulations of LHRH agonists are useful therapies for physicians treating patients with PCa and there may be a preference for the 6-month formulation.
    Therapeutic Advances in Urology 12/2014; 6(6):205-214.
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    ABSTRACT: The aim of the study was to increase the efficiency of treatment for severe symptoms of overactive bladder (OAB) with antimuscarinic drugs in elderly men and women. A total of 341 patients over 65 years of age (average age 69.9; 186 women and 155 men) with severe symptoms of OAB (frequency of incontinence episodes [IEs] ≥ 3/day) underwent examination. Patients were distributed into three main groups: A (n = 58; trospium 60 mg/day + solifenacin 20): three cycles, each cycle 8 weeks, with an 8-week interval; B (n = 55; trospium 30 mg/day + solifenacin 10), regimen was the same as in group A; C (n = 62; trospium 30 mg/day + solifenacin 10) daily during 1 year. The most successful treatment for the clinical and urodynamic symptoms of OAB was observed in group A, without an increase in the quantity or intensity of side effects (IEs = 4.8 (0.9) → 1.4 (0.8); p ≤ 0.01). Groups B and C also demonstrated positive effects for most of the markers for lower urinary tract state with statistical significance p ≤ 0.01. Nonparametric correlation between decrease in IEs and relative number of patients who accurately fulfilled prescriptions was in group A, r = 0.53, p ≤ 0.05; in group B, r = 0.61; p ≤ 0.05; in group C, r = 0.55, p ≤ 0.05. Cyclic therapy with two different spectrum antimuscarinics appears to be effective for controlling severe OAB in elderly patients. One-year cyclic therapy with a trospium and solifenacin combination provides a high compliance level (76-84%). However, continuous therapy with standard doses of trospium and solifenacin results in low adherence and high rates of treatment withdrawals (≥ 66%) despite satisfactory clinical and urodynamic results.
    Therapeutic Advances in Urology 12/2014; 6(6):215-223.
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    ABSTRACT: Priapism is a prolonged erection that persists beyond or is unrelated to sexual stimulation. It is associated with significant morbidity: psychological, socioeconomic, and physical, including pain and potentially irreversible compromise of erectile function. There are three major types of priapism: ischemic, nonischemic, and stuttering. Establishing the type of priapism is paramount to safely and effectively treating these episodes. Ischemic priapism represents a urological emergency. Its treatment may involve aspiration/irrigation with sympathomimetic injections, surgical shunts, and as a last resort, penile prosthesis implantation. Nonischemic priapism results from continuous flow of arterial blood into the penis, most commonly related to penile trauma. This is not an emergency and may be managed conservatively initially, as most of these episodes are self-limiting. Stuttering priapism involves recurrent self-limiting episodes of ischemic priapism. The primary goal of therapy is prevention, but acute episodes should be managed in accordance with guidelines for ischemic priapism. In this paper we review the diagnosis and treatment of the three priapism variants, as well as discuss future targets of therapy and novel targets on the horizon.
    Therapeutic Advances in Urology 12/2014; 6(6):230-244.
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    ABSTRACT: Vulvovaginitis has a known association with urinary tract infections (UTIs) in girls. We hypothesize that vulvovaginitis is a major contributor to UTIs in prepubertal girls by increasing periurethral colonization with uropathogens. Periurethral swabs and urine specimens were obtained from a total of 101 girls (58 with vulvovaginitis and 43 without vulvovaginitis). Specimens were cultured for bacterial growth. The dominant organism in the periurethral swabs and urine cultures was recorded and antibiotic sensitivity profiles were compared. Periurethral swabs from children with vulvovaginitis were associated with a statistically significant increase in uropathogenic bacteria (79% Enterococcus species or Escherichia coli) as the dominant culture compared with swabs from girls without vaginitis (18%) (p < 0.05). In children with vulvovaginitis, 52% of the urine cultures were positive for UTIs, and the dominant organism in the urine cultures matched the species and antibiotic sensitivity profile of the corresponding periurethral swab. Only 11% of the urine cultures from girls without vulvovaginitis were positive for UTIs. Vulvovaginitis may cause UTIs by altering the perineal biome such that there is increased colonization of uropathogens.
    Therapeutic Advances in Urology 12/2014; 6(6):224-229.
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    ABSTRACT: The objective was to conduct a US multicenter, retrospective medical record study examining the effectiveness, safety, and patterns of use of valrubicin for treatment of nonmuscle-invasive bladder cancer (NMIBC) by clinicians since the 2009 reintroduction of valrubicin.
    Therapeutic Advances in Urology 10/2014; 6(5):181-191.
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    ABSTRACT: Peyronie's disease (PD) is a chronic wound-healing disorder characterized by formation of fibrous inelastic scarring of the tunica albuginea resulting in a variety of penile deformities. In most cases, PD is accompanied by a physical and psychological impact. Xiaflex® is an injectable collagenase clostridium histolyticum (CCh) preparation consisting of a predetermined mixture of two distinct collagenases. Recently the US Food and Drug Administration (FDA) approved Xiaflex® for the nonsurgical treatment of men with PD with curvature of 30° or more and tangible scar tissue plaque in their penis.
    Therapeutic Advances in Urology 10/2014; 6(5):192-197.
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is a rare hematologic disorder with affected patients having complications of frequent infections and possible transformation to a more aggressive malignancy. The occurrence of CLL in the bladder is a rare event, with few reported cases. As a result, its aggressiveness and the optimal course for treatment are unknown. Despite this, its presence in the bladder warrants continued surveillance, as recurrence and progression to other bladder malignancies are possible. We present a 71-year-old woman initially diagnosed with CLL who was plagued by recurrent hematuria and dysuria for over a decade, which lead to multiple negative urologic workups. However, these continued workups eventually lead to her diagnosis of bladder CLL with a subsequent finding of carcinoma in situ that was prompted by a suspicious surveillance cystoscopy performed 4 months after her initial bladder diagnosis. Hence, infiltration of CLL in the urinary bladder merits close follow up, including additional urologic procedures.
    Therapeutic Advances in Urology 10/2014; 6(5):198-200.
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    ABSTRACT: Epidemiological data link erectile dysfunction (ED) and benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS), two highly prevalent conditions in aging men, assuming common pathophysiological pathways. Tadalafil 5 mg once daily has been approved for the treatment of men with LUTS with or without comorbid ED. The aim of this review is to provide an overview of current knowledge on the epidemiological and pathophysiological links between ED and LUTS and to focus on tadalafil as a new treatment option in men with BPH-associated LUTS. A Medline search was completed using the Medical Subject Headings (MESH® keywords) 'prostatic hyperplasia' and 'phosphodiesterase inhibitors'. This search revealed 125 relevant references (entire Medline database up to 11 March 2014). The efficacy of tadalafil 5 mg once daily for the treatment of LUTS has been reported by several well-designed studies. Tadalafil improves significantly the total International Prostate Symptom Score (IPSS), the voiding and storage subscores, the IPSS Quality of Life (QoL) and the BPH Impact Index (BII). Its efficacy is irrelevant to the erectile function status of the patients. However, in the majority of these studies tadalafil is not associated with improvement in maximum urine flow or post-void residual volume (PVR). Its safety profile is well established and no new or unexpected adverse events other than those reported in ED studies have been recorded. Tadalafil is today a new treatment alternative to other established drugs for LUTS such as the α-adrenergic antagonists or 5α-reductase inhibitors. However, it is not just an alternative, since sexual adverse events associated with these drugs are avoided and tadalafil is the only drug that can treat both ED and LUTS at the same time.
    Therapeutic Advances in Urology 08/2014; 6(4):135-47.
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    ABSTRACT: The purpose of this article is to review normal developmental bladder physiology in infants and bladder dysfunction in conditions such as neurogenic bladder, posterior urethral valves and high grade vesicoureteric reflux. We contrast the classical concept that bladder function in nontoilet-trained children is thought to be 'reflexive' or 'uninhibited', with the results of more recent research showing that infants most commonly have a stable detrusor. The infant bladder is physiologically distinct from the state seen in older children or adults. The voiding pattern of the infant is characterized by an interrupted voiding stream due to lack of proper urinary sphincter relaxation during voiding. This is called physiologic detrusor sphincter dyscoordination and is different from the pathologic 'detrusor sphincter dyssynergy' seen in patients with neurogenic bladder. Urodynamic abnormalities in neonates born with spina bifida are common and depend on the level and severity of the spinal cord malformation. Upper neuron lesions most commonly lead to an overactive bladder with or without detrusor sphincter dyssynergy while a lower neuron lesion is associated with an acontractile detrusor with possible denervation of the external urinary sphincter. In infants with neurogenic bladder, the role of 'early prophylactic treatment (clean intermittent catheterization and anticholinergics)' versus initial 'watchful waiting and treatment as needed' is still controversial and needs more research. Many urodynamic-based interventions have been suggested in patients with posterior urethral valves and are currently under scrutiny, but their impact on the long-term outcome of the upper and lower urinary tract is still unknown. Cumulative data suggest that there is no benefit to early intervention regarding bladder function in infants with high-grade vesicoureteric reflux.
    Therapeutic Advances in Urology 08/2014; 6(4):148-64.
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    ABSTRACT: In its 2012 global report on tuberculosis, the World Health Organization estimated that 3-7% (range 2.1-5.2%) of new cases and 20% (range 13-26%) of previously treated cases had multidrug-resistant tuberculosis (defined as tuberculosis caused by Mycobacterium tuberculosis isolates that are resistant to rifampicin and isoniazid). In many countries in Eastern Europe and central Asia, 9-32% of new patients and more than 50% of previously treated patients have multidrug-resistant tuberculosis. Ninety-three patients with suspected prostate tuberculosis were enrolled in this study and all underwent prostate biopsy. This method allowed confirmation of diagnosis in 32 patients (34.4%): 23 by histology, six by culture and five by polymerase chain reaction (PCR) (among them, two also had positive culture). The efficiency of an optimized scheme for the therapy of prostate tuberculosis (the second part of the study) was estimated in 53 patients. The first group (25 patients) was treated with a standard scheme of chemotherapy; the second group (28 prostate tuberculosis patients) received ofloxacin in addition for 2 months during the intensive phase. The phase continuation in both groups was identical, with rifampicin and isoniazid administered for 6 months. Optimization of the standard therapy by additional administration of ofloxacin improved results of the treatment in 33.8% of patients.
    Therapeutic Advances in Urology 08/2014; 6(4):129-34.
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    ABSTRACT: Advances in the management of Wilms' tumor have been dramatic over the past half century, not in small part due to the institution of multimodal therapy and the formation of collaborative study groups. While different opinions exist in the management of Wilms' tumors depending on where one lives and practices, survival rates have surpassed 90% across the board in Western societies. With more children surviving into adulthood, the concerns about morbidity have reached the forefront and now represent as much a consideration as oncologic outcomes these days. Innovations in treatment are on the horizon in the form of potential tumor markers, molecular biological means of testing for chemotherapeutic responsiveness, and advances in the delivery of chemotherapy for recurrent or recalcitrant tumors. Other technological innovations are being applied to childhood renal tumors, such as minimally invasive and nephron-sparing approaches. Risk stratification also allows for children to forego potentially unnecessary treatments and their associated morbidities. Wilms' tumor stands as a great example of the gains that can be made through protocol-driven therapy with strenuous outcomes analyses. These gains continue to spark interest in minimization of morbidity, while avoiding any compromise in oncologic efficacy. While excitement and innovation are important in the advancement of treatment delivery, we must continue to temper this enthusiasm and carefully evaluate options in order to continue to provide the highest standard of care in the management of this now highly curable disease.
    Therapeutic Advances in Urology 08/2014; 6(4):165-76.
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    ABSTRACT: The objective of this study was to examine the effects of a green and black tea extract blend [AssuriTEA Men's Health (AMH)] in men with lower urinary tract symptoms (LUTS).
    Therapeutic Advances in Urology 06/2014; 6(3):89-96.
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    ABSTRACT: Iatrogenic injury to the ureter is a potentially devastating complication of modern surgery. The ureters are most often injured in gynecologic, colorectal, and vascular pelvic surgery. There is also potential for considerable ureteral injury during endoscopic procedures for ureteric pathology such as tumor or lithiasis. While maneuvers such as perioperative stenting have been touted as a means to avoid ureteral injury, these techniques have not been adopted universally, and the available literature does not make a case for their routine use. Distal ureteral injuries are best managed with ureteroneocystostomy with or without a vesico-psoas hitch. Mid-ureteral and proximal ureteral injuries can potentially be managed with ureteroureterostomy. If the distal segment is unsuitable for anastomosis then a number of techniques are available for repair including a Boari tubularized bladder flap, transureteroureterostomy, or renal autotransplantation. In rare cases renal autotransplantation or ureteral substitution with gastrointestinal segments may be warranted to re-establish urinary tract continuity. Laparoscopic and minimally invasive techniques have been employed to remedy iatrogenic ureteral injuries.
    Therapeutic Advances in Urology 06/2014; 6(3):115-124.
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    ABSTRACT: Epidemiological studies have shown that lower urinary tract symptoms, including overactive bladder, commonly occur in both men and women, with an age-related increase in both sexes. Vascular endothelial dysfunction and urological symptoms are common in the metabolic syndrome; they also occur during the human ageing process and are independent risk factors for the development of atherosclerosis and hypertension. Pelvic arterial insufficiency may lead to impaired lower urinary tract perfusion and play an important role in the development of bladder dysfunction such as detrusor overactivity and overactive bladder. It seems reasonable, but has not been definitely established clinically, that chronic ischemia-related bladder dysfunction will progress to bladder underactivity. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension, oxidative stress, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. Several types of drug may be able to prevent some of these changes. Even if the α1-adrenoceptor blocker, silodosin, the phosphodiesterase type 5 inhibitor, tadalafil, the β3-α1-adrenoceptor agonist, mirabegron, and the free radical scavenger, melatonin, were unable to prevent the development of neointimal hyperplasia and consequent luminal occlusion in animal models, they all exerted a protecting effect on urodynamic parameters, and on the functional and morphological changes of the bladder demonstrable in vitro. The different mechanisms of action of the drugs suggest that many factors are involved in the pathogenesis of chronic ischemia-induced bladder dysfunction and can be targets for intervention. Since several of the agents tested are used clinically and effectively for relieving lower urinary tract symptoms, the results from animal models of chronic bladder ischemia seem to have translational value. Animal models may be of relevance for designing clinical studies to demonstrate if a certain drug may prevent progression of ischemia-related functional and morphological bladder changes.
    Therapeutic Advances in Urology 06/2014; 6(3):105-114.
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    ABSTRACT: For decades, cytotoxic therapy was considered ineffective for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Earlier therapies such as estramustine and mitoxantrone received regulatory approval based upon improvement in palliative endpoints. In 2004, docetaxel became the first treatment to demonstrate a significant survival benefit in patients with mCRPC based on two randomized phase III studies, TAX327 and SWOG 99-16. Cabazitaxel, a third-generation taxane, was chosen for clinical development based on its decreased affinity for the drug efflux pump, p-glycoprotein, which is a frequent cause of drug resistance in docetaxel-resistant preclinical models. In 2010, cabazitaxel was approved by the US Food and Drug Administration as the first therapy to show a survival benefit for the treatment of patients with docetaxel-refractory mCRPC. This review summarizes the existing literature on the use of cabazitaxel, focusing on its efficacy and safety in combination with prednisone in the treatment of mCRPC, as well as its role in an era of new therapeutic options.
    Therapeutic Advances in Urology 06/2014; 6(3):97-104.
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    ABSTRACT: Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological consequences. Pharmacotherapy of PE with off-label antidepressant selective serotonin reuptake inhibitors (SSRIs) is common, effective and safe. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill an unmet treatment need. The objective of this article is to review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE. MEDLINE, Web of Science, PICA, EMBASE and the proceedings of major international and regional scientific meetings were searched for publications or abstracts published during the period 1993-2012 that used the word 'dapoxetine' in the title, abstract or keywords. This search was then manually cross referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase I, II and III studies, independent postmarketing and pharmacovigilance efficacy and safety studies and drug-interaction studies. Dapoxetine is a potent SSRI which is administered on demand 1-3 h prior to planned sexual contact. It is rapidly absorbed and eliminated, resulting in minimal accumulation, and has dose-proportional pharmacokinetics which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in five industry-sponsored randomized, double-blind, placebo-controlled studies in 6081 men aged at least 18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, Clinical Global Impression of Change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine versus placebo (all p <0.001). The most common treatment-related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (5.9% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use. Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.
    Therapeutic Advances in Urology 10/2012; 4(5):233-51.