Therapeutic Advances in Urology

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ISSN 1756-2880

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Voiding dysfunction encompasses a wide range of urologic disorders including stress urinary incontinence and overactive bladder that have a detrimental impact on the quality of life of millions of men and women worldwide. In recent years, we have greatly expanded our understanding of the pathophysiology of these clinical conditions. However, current gold standard therapies often provide symptomatic relief without targeting the underlying etiology of disease development. Recently, the use of stem cells to halt disease progression and reverse underlying pathology has emerged as a promising method to restore normal voiding function. Stem cells are classically thought to aid in tissue repair via their ability for multilineage differentiation and self-renewal. They may also exert a therapeutic effect via the secretion of bioactive factors that direct other stem and progenitor cells to the area of injury, and that also possess antiapoptotic, antiscarring, neovascularization, and immunomodulatory properties. Local injections of mesenchymal, muscle-derived, and adipose-derived stem cells have all yielded successful outcomes in animal models of mechanical, nerve, or external urethral sphincter injury in stress urinary incontinence. Similarly, direct injection of mesenchymal and adipose-derived stem cells into the bladder in animal models of bladder overactivity have demonstrated efficacy. Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects. Although many challenges remain to be addressed prior to the clinical implementation of this technology, novel stem-cell-based therapies are an exciting potential therapy for voiding dysfunction.
    Therapeutic Advances in Urology 02/2015; 7(1):22-40. DOI:10.1177/1756287214553968
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    ABSTRACT: Desmoid tumors are rare soft-tissue masses originating from the proliferation of fibroblasts in the fibroconnective tissues. Intra-abdominal desmoid tumors pose special diagnostic challenge due to multiplicity of differential diagnoses, and difficulty to well characterize the lesions on imaging studies. Desmoid tumors can have atypical presentation making clinical correlation challenging to unsuspecting urologists. Only a few cases have been reported in the urology literature. In this report, we present a case of desmoid tumor presenting with gross hematuria.
    Therapeutic Advances in Urology 02/2015; 7(1):49-51. DOI:10.1177/1756287214553969
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    ABSTRACT: Enzalutamide is an oral androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling pathway. In the randomized phase III AFFIRM study, significant improvements in survival versus placebo were observed when enzalutamide was used as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) following prior treatment with docetaxel. Additional benefits included significant delay in time to first skeletal-related event, and improvement in several measures of pain and health-related quality of life. Treatment effects were consistent across all prespecified subgroups. The phase III PREVAIL study evaluated enzalutamide versus placebo in patients with mCRPC who had not received chemotherapy. Enzalutamide significantly decreased the risk of radiographic progression and death. There were also significant improvements in all secondary and prespecified exploratory endpoints, including delayed initiation of chemotherapy, reduction in risk of first skeletal-related event and a high percentage of patients with objective response compared with placebo. Enzalutamide was also studied in hormone naïve patients (as monotherapy) in a small, open-label phase II study in patients with prostate cancer who were eligible for androgen-deprivation therapy. A prostate-specific antigen (PSA) response, defined as ⩾80% decline in PSA level from baseline at week 25, was achieved in 92.5% of patients. Long-term follow up is ongoing. Despite differences between these three trials, enzalutamide displayed a favorable safety profile in all three patient populations. Similar rates of adverse events between the enzalutamide and placebo groups were observed in AFFIRM and PREVAIL, with fatigue, diarrhea, back pain and hot flashes being more common with enzalutamide than with placebo. Hypertension was reported at a higher rate in the enzalutamide group than in the placebo group in PREVAIL. Breast-related disorders associated with enzalutamide treatment were also reported in the Monotherapy trial. Few seizures were reported in any trial. Enzalutamide is being studied in several early disease state populations.
    Therapeutic Advances in Urology 02/2015; 7(1):9-21. DOI:10.1177/1756287214555336
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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. DOI:10.1177/1756287214542096
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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. DOI:10.1177/1756287214542097
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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. DOI:10.1177/1756287214544896
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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. DOI:10.1177/1756287214545328
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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. DOI:10.1177/1756287214542418
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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. DOI:10.1177/1756287214535461
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    ABSTRACT: Introduction: 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. Method: This article presents a comprehensive review of the updated information on the use of Xiaflex® for the nonsurgical treatment of PD. Results: Mean improvements in penile curvature ranging from 29% to 34% and in bother domain scores have been reported. The majority of the reported adverse effects are mild or moderate and 79% resolve without intervention. Conclusion: The combined results of these trials have led to the FDA approval of CCh for the treatment of PD. However, the long-term effects and results need further investigation, with large follow-up series. Considering these results, future perspectives will probably result in the use of a combined or sequential therapy including CCh.
    Therapeutic Advances in Urology 10/2014; 6(5):192-197. DOI:10.1177/1756287214537331
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    ABSTRACT: Objectives: 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. Methods: Patients ≥ 18 years with NMIBC who received had one or more instillations of valrubicin (October 2009- September 2011) were eligible. The primary endpoint was event-free survival (EFS). Safety and tolerability were also assessed. Results: The medical records of 113 patients met the inclusion criteria; 100 patients (88.5%) completed valrubicin treatment. The median age was 75 years (range 42-95 years). The median NMIBC duration was 31 months since diagnosis: 51.3% (58/113) had carcinoma in situ (CIS) alone, and 31.9% (36/113) had unspecified NMIBC. Most patients, 94.7% (107/113), had more than three valrubicin instillations and 70.8% (80/113) completed a full course. The EFS rate (95% confidence interval) was 51.6% (40.9-61.3%), 30.4% (20.4-41.1%), and 16.4% (7.9-27.5%) at 3, 6, and 12 months, respectively. Median time to an event was 3.5 (2.5-4.0) months after the first valrubicin instillation. Local adverse reactions (LARs) were experienced by 49.6% (56/113) of patients; most LARs were mild (93.6%). The most frequent LARs were hematuria, pollakiuria, micturition urgency, bladder spasm, and dysuria. In total, 4.4% (5/113) of patients discontinued valrubicin because of adverse events or LARs. Conclusions: Data from the present retrospective study are consistent with previous prospective clinical trials that demonstrated valrubicin effectiveness and tolerability for select patients with CIS, before considering cystectomy. Additional prospective studies are warranted to evaluate valrubicin safety and efficacy in the broader patient population with NMIBC.
    Therapeutic Advances in Urology 10/2014; 6(5):181-191. DOI:10.1177/1756287214541798
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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. DOI:10.1177/1756287214529005
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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. DOI:10.1177/1756287214531639
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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. DOI:10.1177/1756287214528745
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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. DOI:10.1177/1756287214528023
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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. DOI:10.1177/1756287214528557