ISMH » Scientific Spotlight http://www.ismh.org/en International Society for Men's Health Tue, 14 May 2013 08:53:36 +0000 en-US hourly 1 http://wordpress.org/?v=3.5.1 Latest Update on Prostate Cancer Screening at the AUA Meeting, May 2013 http://www.ismh.org/en/ismh-news/latest-update-on-prostate-cancer-at-the-aua-meeting-may-2013/ http://www.ismh.org/en/ismh-news/latest-update-on-prostate-cancer-at-the-aua-meeting-may-2013/#comments Mon, 13 May 2013 20:38:32 +0000 Daniela http://www.ismh.org/en/?p=3547 At the American Urological Association Annual Meeting earlier this week, new guidelines from the AUA now recommend that men aged 55 to 69 who are considering prostate cancer screening discuss the benefits and potential harms of screening with their doctors, then to proceed based upon personal values and preferences.  This recommendation is based upon high-quality evidence that suggests the screening benefit over 2- to 4-year intervals would allow 1 man per 1,000 to avert death from prostate cancer over a decade, yet the benefit extrapolated over a man's lifetime may actually be greater. 

The AUA guidelines state that screening for prostate cancer in men less than 40 years of age is not recommended, nor is routine screening in men 40 to 54 years of age at average risk.  To reduce harms of screening, a screening interval of 2 years may be preferable over annual screening in low-risk men who have engaged in shared-decision making with their physician.  Lastly, routine prostate cancer screening in men over 70, or in men with a less than 10- to 15-year life expectancy is not recommended.

Reference: American Urological Association Annual Meeting, May 4-8, 2013, San Diego, California, USA

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Osteoporosis management program in patients with prostate cancer receiving androgen deprivation therapy http://www.ismh.org/en/scientific-spotlight/osteoporosis-management-program-in-patients-with-prostate-cancer-receiving-androgen-deprivation-therapy/ http://www.ismh.org/en/scientific-spotlight/osteoporosis-management-program-in-patients-with-prostate-cancer-receiving-androgen-deprivation-therapy/#comments Mon, 13 May 2013 20:05:11 +0000 Daniela http://www.ismh.org/en/?p=3551 Approximately one third of patients with prostate cancer receive androgen deprivation therapy (ADT). This treatment is associated with higher incidence of fractures and increased mortality of fractures. However, only a minority of patients receiving ADT has their bone mineral density (BMD) documented before or after initiation of ADT. Therefore, the aim of this study was to determine whether the implementation of a screening and treatment protocol reduced the rate of osteoporotic fractures in men with prostate cancer receiving ADT.

This study included 1482 patients with prostate cancer receiving leuprolide identified in the electronic medical system of Kaiser Permanente Southern California. Of them, 1071 were included in the Healthy Bone Program (HBP) comprising BMD measurement by dual energy X-ray absorptiometry and treatment. The indications of anti-osteoporotic treatment were established using T-score corresponding to the number of standard deviations below the mean in young healthy adult men. Men with T-score ≥-2.5 were advised on smoking cessation, regular exercise, adequate calcium intake (1200 mg/d) and adequate vitamin D intake (400-800 IU/d). Men with T-score <-2.5 were also treated with pharmacological intervention (mainly bisphosphonates). The remaining 411 men received standard care. Strict exclusion criteria were used to reduce the selection bias.

The men who were included in the HBP had much lower incidence of hip fracture (5 vs 18 fractures per 1000 person-years). After adjustment for confounders, patients who were not enrolled in the HBP had a fourfold higher risk of hip fracture compared with the HBP patients (hazard risk = 4.19, 95% confidence interval 1.92 – 9.13, p<0.001).

In this study men with prostate cancer receiving ADT and enrolled in an active screening and treatment protocol experienced 72% lower rate of hip fracture compared with the nonscreened group. This difference may seem astonishingly high; however, two facts need to be remembered. Some older men have low BMD and high risk of fracture. ADT accelerates bone turnover leading to a rapid bone loss associated with a deterioration of bone microarchitecture and higher bone fragility. This rapid bone loss may be particularly dangerous in men with low BMD at baseline. ADT-induced hypogonadism may also result in rapid loss of muscle mass and strength leading to a higher risk of falling. Thus, the detection and treatment of men with low BMD may decrease markedly the risk of fracture. Moreover, the implementation if lifestyle changes may have a beneficial effect on bone and muscle.

Some limitations of the study have to be recognized: retrospective identification of patients, observational design, potential imbalance in risk factors and medical care between two groups of men. However, despite these limitations, the paper and accompanying comment are important because they raise two major points. Firstly, ADT increases bone fragility. Thus, critical judgment of indications for ADT is necessary before its initiation in order to avoid the severe adverse effects. Secondly, the implementation of an osteoporosis management program in patients with prostate cancer receiving ADT may have a beneficial effect.

Reference: Zhumkhawala AA, Gleason JM, Cheetham TC, Niu F, Loo RK, Dell RM, Jacobsen SJ, Chien GW. Osteoporosis management program decreases incidence of hip fracture in patients with prostate cancer receiving androgen deprivation therapy Urology. 2013 May; 81(5):1010-7.

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Naftopidil in the Management of BPH http://www.ismh.org/en/scientific-spotlight/naftopidil-in-the-management-of-bph/ http://www.ismh.org/en/scientific-spotlight/naftopidil-in-the-management-of-bph/#comments Wed, 01 May 2013 12:08:34 +0000 Daniela http://www.ismh.org/en/?p=3544 Naftopidil has affinity for both α1A- and α1D-adrenoreceptors for the treatment of benign prostatic obstruction and benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS).  It was originally developed as an α-adrenoceptor antagonistic anti-hypertensive drug.  It has been evaluated in both prazosin-controlled and double-blind-controlled trials in Japan that verified dose-dependent effects, and therefore has had an indication for treatment of BPH in Japan, China, and South Korea.  Several tamsulosin-controlled trials have suggested a potentially higher efficacy for alleviating storage symptoms with naftopidil.  The optimal dose is 50-75mg per day according to characteristics including baseline IPSS.  Well-designed randomized trials are warranted to confirm long-term outcomes regarding management of men with storage symptoms including nocturia, through comparisons of quality of life measures with other α-adrenergic blockers.

Reference: Hara N, Mizusawa T, Obara K, Takahashi K.  The role of naftopidil in the management of benign prostatic hyperplasia.  Ther Adv Urol 2013;5(2)111-119.

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Udenafil in the Management of ED http://www.ismh.org/en/scientific-spotlight/udenafil-in-the-management-of-ed/ http://www.ismh.org/en/scientific-spotlight/udenafil-in-the-management-of-ed/#comments Wed, 01 May 2013 12:03:29 +0000 Daniela http://www.ismh.org/en/?p=3542 Udenafil is a novel PDE5-inhibitor approved for treatment of ED in Korea.  It has an onset of action of 1-1.5 hours and a half-life of 11-13 hours, suitable for both on-demand and daily use.  It has been tested across various levels of trials (through Phase III studies) in subjects with ED and concomitant diabetes mellitus, hypertension, and BPH.  It appears to be safe and well-tolerated, resulting in significant improvements in men with ED according to IIEF parameters.

Commonly reported adverse effects include headache, facial flushing, and febrile sensation, and none were considered to be of moderate or severe intensity.  In a multiple-dose study, a color discrimination abnormality was reported that affected the blue-green region of the visual spectrum, yet this adverse effect spontaneously resolved upon successive testing defined as 1.5 hours after the fourth dose.  There were no clinically significant findings in routine laboratory parameters including platelet aggregation tests, bleeding time, or semen analysis.

Udenafil appears to have a longer onset time compared with vardenafil and a shorter duration compared to tadalafil.  Larger cohort, multi-ethnic trials will be required to more accurately assess its efficacy for worldwide use.

Reference: Kang SG, Kim JJ.  Udenafil: efficacy and tolerability in the management of erectile dysfunction.  Ther Adv Urol 2013;5(2):101-110.

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Personalized PSA Testing May Reduce Prostate Biopsies http://www.ismh.org/en/scientific-spotlight/personalized-psa-testing-may-reduce-prostate-biopsies/ http://www.ismh.org/en/scientific-spotlight/personalized-psa-testing-may-reduce-prostate-biopsies/#comments Wed, 01 May 2013 12:01:59 +0000 Daniela http://www.ismh.org/en/?p=3540 Recent studies have identified genetic variants associated with increased PSA levels and prostate cancer risk, raising the possibility of diagnostic bias.  By correcting for these variants, it has been postulated that a “personalized� cut-off for PSA levels could be determined which could help to better stratify patients for prostate biopsy to rule out cancer.  Genetic correction of PSA was performed by dividing a subject's PSA value by his combined genetic risk. 

Four single nucleotide polymorphisms associated with PSA levels have been identified in healthy subjects without prostate cancer.  Genetic correlation of PSA results in 964 Caucasian men was associated with a significantly decreased percentage of men reaching biopsy thresholds, estimating a 15% to 20% relative reduction in biopsies using a threshold of 2.5ng/ml or greater or 4.0ng/ml or greater, respectively.  In addition, genetic correlation could results in an 18% to 22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses.

Limitations of this study include a small cohort of only Caucasian men, suggesting the need for a larger study across various ethnicities.  The influence of genetic correction on clinical outcomes requires further prospective study in a large, independent cohort.  Lastly, the applicability of cost-effectiveness must be considered, since genetic testing may not be readily available across practices.

Reference: Helfand BT, Loeb S, Hu Q, et al.  Personalized prostate specific antigen testing using genetic variants may reduce unnecessary prostate biopsies.  J Urol 2013;189:1697-1701.

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Effects of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction http://www.ismh.org/en/scientific-spotlight/effects-of-testosterone-replacement-on-response-to-sildenafil-citrate-in-men-with-erectile-dysfunction/ http://www.ismh.org/en/scientific-spotlight/effects-of-testosterone-replacement-on-response-to-sildenafil-citrate-in-men-with-erectile-dysfunction/#comments Thu, 18 Apr 2013 16:30:20 +0000 Daniela http://www.ismh.org/en/?p=3528 Testosterone is a major regulator of sexual desire, spontaneous sexual thoughts, motivation, attentiveness to erotic stimuli, and sexual activity in men. Experimental studies show that testosterone regulates penile nitric oxide synthase and blood flow. These data lead to speculation that, in men with erectile dysfunction (ED), normal testosterone level is necessary to achieve an optimum response to phosphodiesterase type 5 (PDE5) inhibitors.

This randomized, parallel group trial was performed in 140 men aged 40 to 70 with ED and low levels of total or free testosterone levels (<330 ng/dl or <50 pg/ml, respectively). First, dose of sildenafil was optimized for 3 to 7 weeks (25-100 mg/d). Then, participants were randomized (1:1) to testosterone (Testim, Auxilium Pharmaceuticals, Malvern) or placebo gel. Men were treated for 14 weeks and testosterone was adjusted on the basis of testosterone measurements. During the treatment, erectile and sexual functions as well as ED-related quality of life were assessed using standardized and validated questionnaires.

During the first phase, sildenafil administered alone increased testosterone levels by ~100 ng/dl. Later on, in the testosterone-treated group, testosterone levels increased further to the average level of 649 ng/dl. Sildenafil alone induced a substantial increase in all domains of the International Index of Erectile Function (IIEF) such as erectile function, sexual desire, orgasmic function, or intercourse satisfaction. Sildenafil alone also improved substantially all domains of the Sexual Encounter Profile (SEP), e.g. frequency of sexual encounters, vaginal penetration or ejaculation. Further, sildenafil also improved the ED-related quality of life. Importantly, there was no difference between men who did or did not take testosterone (in addition to sildenafil) as concerns the evaluated parameters of sexual function. The analysis limited to men who completed 14 weeks of treatment provided similar results. The effect of testosterone on ED did not vary by the testosterone levels, age or body mass index.

Thus, sildenafil plus testosterone did not improve sexual function compared with sildenafil plus placebo. This may seem surprising in light of preclinical data. However, sildenafil may have increased testosterone levels higher than the upper limit of dose-response relationship of testosterone for erectile function. Testosterone and sildenafil may share common mechanistic pathways and the optimized dose of sildenafil may have maximally induced these pathways. The results are not related to methodological problems: this was a randomized, double-blind and placebo-controlled trial, dropout rate was low, patients responded robustly to sildenafil, duration of testosterone treatment was sufficient to induce a therapeutic response.

Thus, in summary, these results do not support the routine addition of testosterone therapy for improving erectile response to selective PDE5 inhibitors in men with ED who have low testosterone levels.

Reference: Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, Mazer NA, KNapp PE, Hanka S, Lakshman KM, Ulloor J, Zhang A, Orwoll K, Eder R, Collins L, Mohammed N, Rosen RC, DeRogatis L, Bhasin S. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012 157(10):681-91.

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Erectile dysfunction is associated with higher cardiovascular risk and all cause mortality http://www.ismh.org/en/scientific-spotlight/erectile-dysfunction/erectile-dysfunction-is-associated-with-higher-cardiovascular-risk-and-all-cause-mortality/ http://www.ismh.org/en/scientific-spotlight/erectile-dysfunction/erectile-dysfunction-is-associated-with-higher-cardiovascular-risk-and-all-cause-mortality/#comments Wed, 20 Feb 2013 17:10:58 +0000 Daniela http://www.ismh.org/en/?p=3518 Cardiovascular (CV) disease and erectile dysfunction (ED) share common risk factors, whereas evidence-based studies have identified pathophysiological links as endothelial dysfunction and inflammation. Thus, identifying ED may be a useful predictor of future CV events.

Vlachopoulos et al. (1) performed the meta-analysis of 14 studies including jointly 92757 men (various outcomes have not necessarily been studied in all men). Total CV events were defined as CV death, myocardial infarction, revascularization, cerebrovascular events (stroke, transient ischemic attacks, intracranial hemorrhage), peripheral vascular disease, angina, heart failure and arrhythmia. ED was associated with a significantly higher (by 44%) risk of total CV events. The risk was significantly increased in the intermediate-risk group (by 51%) and in the high-risk group (by 30%), but not in the low-risk group. In an analysis performed in the studies in which the analyses were adjusted for main CV confounders, the increase in the risk of total CV event associated with ED was similar to the overall combined estimated risk. It shows that the higher CV risk in men with ED was independent of their higher baseline CV risk. The increase in the CV risk associated with ED was higher in studies in which ED was diagnosed with a validated questionnaire (by 61%) compared with a single question (by 27%).

ED was also associated with a significantly higher risk of myocardial infarction (by 62%) and of cerebrovascular event (by 39%). ED was associated with a significantly higher all-cause mortality (by 25%), mainly in men with known CV disease, but not with CV mortality. The findings of the meta-analyses were not related to the publication bias. Finally, meta-regression analyses showed that ED was predictive of CV events mainly in younger men, smokers as well as in men with higher total cholesterol and lower HDL-cholesterol levels.

Thus, screening and diagnosing ED can be important for primary prevention in the clinical practice because ED assessment offers an easy, low-cost alternative for CV biomarkers. The risk conferred by ED on the CV events is of a magnitude similar to that of the risk conferred by established risk predictors such as hypertension or dyslipidemia. ED can describe the CV risk particularly in men belonging to the intermediate-risk category. This group requires further risk reclassification and ED may be an additional predictor permitting to better assess the individual CV risk. Furthermore, the use of a validated questionnaire improves the diagnosis of ED and provides a stronger association between ED and the CV risk.

Overall these findings show that the assessment of ED using a validated method may help to estimate the CV risk in the clinical practice.

Reference: Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes. 2013 6:99-109.

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Zoledronic acid decreases the risk of vertebral fracture in osteoporotic men http://www.ismh.org/en/scientific-spotlight/osteoporosis/zoledronic-acid-decreases-the-risk-of-vertebral-fracture-in-osteoporotic-men/ http://www.ismh.org/en/scientific-spotlight/osteoporosis/zoledronic-acid-decreases-the-risk-of-vertebral-fracture-in-osteoporotic-men/#comments Mon, 31 Dec 2012 12:15:28 +0000 ismh http://www.ismh.org/en/?p=3492 Osteoporotic fractures in men are a major health issue. However, studies involving men with osteoporosis have focused on the surrogate outcomes such as bone mineral density (BMD) and biochemical bone turnover markers (BTM). By contrast, data from randomized, double-blind, clinical trials assessing anti-fracture efficacy in men are lacking. Therefore, the recent multicenter randomized prospective trial assessing the effect of zoledronic on the risk of vertebral fracture in osteoporotic men as a primary end point is of particular interest. Previously, zoledronic acid reduced highly significantly fracture incidence in postmenopausal women and increased BMD in several studies carried out in men with low BMD.

This study was performed in 1199 men aged 50 to 85. Eligible men without fracture had BMD T-score≤-2.5 at total hip, femoral neck or lumbar spine. Eligible men with fracture had BMD T-score≤-1.5 and one to three vertebral fractures. (T-score was calculated as the number of SDs below or above the mean in young men.) Men were randomly assigned to receive zoledronic acid at a dose of 5 mg or placebo administered as a 15 to 30 minute i.v. infusion at baseline and month 12. All men received daily calcium (1000-1500 mg) and vitamin D (800-1200 IU). Men were followed up for 24 months; almost 90% of men completed the study.

Vertebral fracture incidence was 67% lower in the zoledronic acid group compared with the placebo group (RR= 0.33, 95% confidence interval: 0.16-0.70, p=0.002). Loss of height was smaller in the zoledronic acid group vs placebo group (2.2 vs 4.5 mm, p=0.002). Zoledronic acid induced a significant increase in BMD at the lumbar spine, total hip and femoral neck. The difference vs the placebo group was statistically significant for all the skeletal sites. Serum levels of bone formation markers (N-terminal propeptide of type I procollagen [PINP], bone-specific alkaline phosphatase) were significantly lower in men who received zoledronic acid than in men who received placebo. Levels of bone resorption markers (serum C-terminal telopeptide of type I collagen, urinary N-terminal telopeptide of type I collagen) were also significantly lower in men receiving zoledronic acid. The effect of zoledronic acid on the fracture incidence, BMD and BTM levels (except PINP) was similar in men with testosterone levels of >350 ng/dl and in men with testosterone levels of 350 ng/dl or less.

The most frequent adverse effect of zoledronic acid was the influenza-like syndrome (pyrexia, myalgia, arthralgia, headaches, chills, pain in the extremities). It occurred in 15% of men and subsided spontaneously. No case of osteonecrosis of the jaw and no case of subtrochanteric or atypical fracture were observed. No significant differences were observed between the groups with respect to death, cardiac arrhythmias or renal dysfunction, except for myocardial infarction which was slightly more frequent in the zoledronic acid group. However, the analysis of each case showed that these events were not related to the study drug.

A key strength of this study was a population that was large enough to detect the anti-fracture efficacy of zoledronic acid in the osteoporotic men in the framework of a placebo-controlled, randomized, prospective trial. Zoledronic acid increased BMD and decreased bone turnover rate. The effect of zoledronic acid was independent of total testosterone levels. The reduction of fracture risk, the increase in BMD, the decrease in bone turnover rate and the safety profile were similar to those found in postmenopausal women treated with zoledronic acid. These results provide support for the value of antiresorptive therapy in osteoporotic men. They may also contribute to a better definition of treatment recommendations of osteoporosis in men.

Reference: Boonen S et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med 2012, 367:1714-1723.

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Sex Disparities in Cancer Mortality: The Risks of Being a Man in the US http://www.ismh.org/en/scientific-spotlight/cancer/sex-disparities-in-cancer-mortality-the-risks-of-being-a-man-in-the-us/ http://www.ismh.org/en/scientific-spotlight/cancer/sex-disparities-in-cancer-mortality-the-risks-of-being-a-man-in-the-us/#comments Fri, 28 Dec 2012 19:05:00 +0000 ismh http://www.ismh.org/en/?p=3490 A novel descriptive epidemiologic study that will be published in the Journal of Urology is the first study to quantify the differential mortality rates between sexes from non-gender-specific cancers and compare their cancer stage distribution.  This study hypothesized that men die more commonly from their cancers than their female counterparts, even after the increased male incidence is accounted for.

Between 1975 and 2004, the National Institutes of Health reported the total cancer burden in the US was higher in males compared to females with an incidence ratio of 1.14; when sex-specific cancers were excluded, the ratio increased to 1.77.  Moreover, the yearly male to female cancer mortality ratio was 1.89.

The authors determined that over the last 10 years, the number of men diagnosed with cancer has consistently been 1.5 times greater than the rate for women.  While the overall mortality rates attributable to cancer have decreased over 10% for both men and women, the mortality rate for men still exceeds that for women, even for the same type of cancer.  While a descriptive study does not explain the reasons for gender differences in oncologic outcomes, previous studies have highlighted differences in modifiable risk factors, differences in healthcare utilization, and intrinsic biological differences between the sexes.  In the US, 27% of men report not being evaluated by a physician within the last year compared to 14% of women. 

In summary, the authors concluded that men develop and die more often from cancers that should affect men and women equally.  However, the number of men diagnosed with non-gender-specific cancer is 50% higher than the number of women diagnosed with cancer.  After controlling for higher male incidence of cancers, men have a 12.6% higher mortality rate than women for the same types of cancer.

Reference: Najari BB, Rink M, Li PS, Karakiewicz PI, Scherr DS, Shabsigh R, Meryn S, Schlegel PN, Shariat SF.  Sex disparities in cancer mortality: the risks of being a man in the US.  J Urol 2012, doi:10.1016/j.juro.2012.11.153.

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Using MRI to Validate Scoring System for Prostate Cancer http://www.ismh.org/en/scientific-spotlight/prostate-cancer/using-mri-to-validate-scoring-system-for-prostate-cancer/ http://www.ismh.org/en/scientific-spotlight/prostate-cancer/using-mri-to-validate-scoring-system-for-prostate-cancer/#comments Sun, 16 Dec 2012 18:59:54 +0000 ismh http://www.ismh.org/en/?p=3488 Until recently, wide variations in acquisition protocols and the lack of robust diagnostic criteria make magnetic resonance imaging (MRI) detection of prostate cancer (PCa) one of the most challenging fields in radiology and urology.  A recent trial sought to validate the recently proposed European Society of Urogenital Radiology (ESUR) scoring system for multiparametric MRI (mpMRI) of the prostate, taking advantage of the development of MRI/transrectal ultrasonography (TRUS) fusion technology to evaluate the predictive values of the ESUR scoring system in a cohort of 129 consecutive patients with a total of 1514 cores.

A prospective study from May to November 2011, 129 consecutive patients with a history of negative TRUS-guided biopsies of the prostate were referred for repeat biopsies. A total of 129 consecutive patients (mean age: 64.7 ± 6.9 yr [range: 47–79]) were enrolled for repeat biopsies (mean number of prior biopsy sessions: 1.3 ± 0.7 [range: 1–4]). Digital rectal examination (DRE) was unremarkable in 107 patients and suspicious in 22 patients (nodule smaller than half a lobe). Mean prostate-specific antigen (PSA) at biopsy was 9.6 ± 5.9 ng/ml (range: 2.7–40.0), and prostate volume (MRI estimate) was 51.1 ± 28.1 cm3 (range: 12–192).  A threshold of ESUR-S (EUR Score Sum) ≥ 9 exhibited the following characteristics: sensitivity: 73.5%; specificity: 81.5%; positive predictive value: 38.2%; negative predictive value: 95.2%; and accuracy: 80.4%.

Although this trial was not designed to compare repeat biopsy strategies, more targeted cores than random systematic cores were found to be positive for cancer (36.3% compared with 4.9%, p < 0.00001).  Given the inherent challenges of choosing patients for repeat biopsy, the ESUR scoring system was shown to provide clinically relevant stratification of the risk of showing PCa in a given location.  Although the ESUR system was based on literature evidence and consensus, it still lacked validation in a real-life setting.  Only a few cancers were detected solely by random core biopsy specimens, as opposed to the larger yield of cores targeted at mpMRI-suspicious locations.  The validation of the ESUR scoring system and precise targeting of TRUS-guided biopsies now provide convincing leverage in the challenging field of PCa diagnosis.

Reference: Portalez D, Mozur P, Cornud F, et al.  Validation of the European Society of Urogenital Radiology Scoring System for Prostate Cancer Diagnosis on Multiparametric Magnetic Resonance Imaging in a Cohort of Repeat Biopsy Patients.  Eur J Urol 2012;62:986-996.

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