Raimondo Giardina

Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis

Abstract Lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in adult men. Several drugs used for LUTS/BPO may strongly affect sexual function and bother. The aim of this systematic review and meta-analysis was to evaluate the impact of combination therapy with alpha-blockers (AB), 5-alpha reductase inhibitors (5-ARI) on the risk of erectile dysfunction(ED) and libido alterations (LA) from randomized clinical trial (RCT). Based on the inclusion and exclusion criteria, five RCTs involving 6131 patients were included in the analysis. According to the analysis, the overall prevalence of ED and LA were significantly greater in the combination treatment group than in the AB group (7.93% versus 4.66%; OR 1.81; p < 0.0001 and 3.69% versus 2.36%; OR 1.58; p = 0.003, respectively). The combination therapy increased the risk of ED compared to monotherapy with 5-ARI (7.93% versus 6.47%; OR 1.25; p = 0.04) but not the risk of LA (3.51% versus 3.37; OR 1.03; p = 0.84). In our systematic meta-analysis, we demonstrated that combination therapy with ABs and 5-ARIs was associated with significantly higher risk of ED and LA compared with single monotherapy. Combination therapy showed similar risk of LA compared with 5-ARI monotherapy.

Determinants of Sexual Impairment in Multiple Sclerosis in Male and Female Patients with Lower Urinary Tract Dysfunction: Results from an Italian Cross‐Sectional Study

INTRODUCTION Sexual dysfunction (SD) is prevalent in multiple sclerosis (MS) patients and affects quality of life. Furthermore, lower urinary tract dysfunction (LUTD) is common in MS patients. AIMS This study aims to evaluate the relationship between SD, neurological disability, depression, anxiety, and urodynamic alterations in patients with MS and LUTD. METHODS From January 2011 to September 2013, 135 consecutive patients with MS in remission phase and LUTD underwent first urodynamic examination, according to the International Continence Society criteria. Depression and anxiety were evaluated with the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A), neurological impairment was assessed using the Expanded Disability Status Scale (EDSS), and SD was investigated with the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-15). MAIN OUTCOME MEASURES Multivariate logistic regression analyses were carried out to identify variables for predicting female sexual dysfunction (FSD) (FSFI < 26.55), male SD (IIEF-15 < 60), or moderate-severe erectile dysfunction (IIEF-EF ≤ 16), after adjusting for confounding factors. RESULTS Total IIEF-15 and all subdomains (all P < 0.01), total FSFI, FSFI-arousal, FSFI-lubrication, and FSFI-orgasm (all P < 0.05) were lower in subjects with EDSS ≥ 4.5. We found inverse relationship between IIEF-15 and relative subdomains with EDSS (all P < 0.01) and between FSFI and relative subdomains with EDSS (all P < 0.01), HAM-D (all P < 0.01), and HAM-A (all P < 0.01). Continuous EDSS (odds ratio [OR] = 1.54; P = 0.03) and categorical EDSS (≥4.5) (OR = 6.0; P = 0.03), HAM-D (OR = 4.74; P = 0.03), and HAM-A (OR = 4.10; P = 0.02) were significantly associated with FSD (FSFI < 26.55). Detrusor overactivity (DO) was an independent predictor of moderate-severe ED (IIEF-EF ≤ 16) (OR = 2.03; P < 0.01), and of FSD (OR = 9.73; P = 0.04). CONCLUSIONS Neurological disability, depression and DO are significantly predictive of SD in MS patients, irrespective of gender. An EDSS ≥ 4.5 may significantly predict the presence of SD.

A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Prostate Health Index and 4-Kallikrein Panel Score in Predicting Overall and High-grade Prostate Cancer

Abstract Markers for prostate cancer (PCa) have progressed over recent years. In particular, the prostate health index (PHI) and the 4‐kallikrein (4K) panel have been demonstrated to improve the diagnosis of PCa. We aimed to review the diagnostic accuracy of PHI and the 4K panel for PCa detection. We performed a systematic literature search of PubMed, EMBASE, Cochrane, and Academic One File databases until July 2016. We included diagnostic accuracy studies that used PHI or 4K panel for the diagnosis of PCa or high‐grade PCa. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. Twenty‐eight studies including 16,762 patients have been included for the analysis. The pooled data showed a sensitivity of 0.89 and 0.74 for PHI and 4K panel, respectively, for PCa detection and a pooled specificity of 0.34 and 0.60 for PHI and 4K panel, respectively. The derived area under the curve (AUC) from the hierarchical summary receiver operating characteristic (HSROC) showed an accuracy of 0.76 and 0.72 for PHI and 4K panel respectively. For high‐grade PCa detection, the pooled sensitivity was 0.93 and 0.87 for PHI and 4K panel, respectively, whereas the pooled specificity was 0.34 and 0.61 for PHI and 4K panel, respectively. The derived AUC from the HSROC showed an accuracy of 0.82 and 0.81 for PHI and 4K panel, respectively. Both PHI and the 4K panel provided good diagnostic accuracy in detecting overall and high‐grade PCa.

Relationship between urodynamic findings and sexual function in multiple sclerosis patients with lower urinary tract dysfunction

Sexual dysfunction (SD) is prevalent in multiple sclerosis (MS) patients and affects quality of life. Furthermore, lower urinary tract dysfunction (LUTD) is common in MS patients. Our aim was to determine the relationship between urodynamic findings and SD in a cohort of MS patients with LUTD.

Confirmatory biopsy of men under active surveillance: extended versus saturation versus multiparametric magnetic resonance imaging/transrectal ultrasound fusion prostate biopsy

Abstract Objective: The aim of this study was to evaluate the detection rate for clinically significant prostate cancer (PCa) after multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion biopsy versus extended biopsy or saturation prostate biopsy (SPBx) in men enrolled on active surveillance (AS). Materials and methods: From May 2013 to January 2016, 100 men with very low-risk PCa were enrolled on AS. Eligible criteria were: life expectancy greater than 10 years, cT1c, prostate-specific antigen (PSA) below 10 ng/ml, PSA density less than 0.20 ng/ml², three or fewer unilateral positive biopsy cores, Gleason score (GS) equal to 6 and greatest percentage of cancer in a core 50% or lower. All patients underwent 3.0 T pelvic mpMRI before confirmatory transperineal extended biopsy (20 cores) and SPBx (median 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (median four cores) of suspicious lesions [Prostate Imaging Reporting and Data System (PI-RADS) 3–5]. Clinically significant PCa was defined as the presence of at least one core with a GS of 4 or higher. Results: After confirmatory biopsy, 16 out of 60 (26.6%) patients showed significant PCa. Targeted biopsy of PI-RADS 4–5 versus PI-RADS 3–5 lesions diagnosed six out of 16 (37.5%) and 12 out of 16 (87.5%) significant PCa, respectively, with two false positives (5%). The detection rate for significant PCa was equal to 68.8% on mpMRI/TRUS fusion biopsy, 75% on extended biopsy and 100% on SPBx. mpMRI/TRUS targeted biopsy and extended biopsy missed five out of 16 (31.2%) and four out of 16 (25%) PCa, respectively. Conclusions: Although mpMRI may improve the diagnosis of significant PCa in men under AS, SPBx had a higher detection rate for clinically significant PCa.

Comparison between Briganti, Partin and MSKCC tools in predicting positive lymph nodes in prostate cancer: a systematic review and meta-analysis

Abstract Objective: The aim of this study was to analyze the discriminative capabilities of Briganti, Partin and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms in predicting lymph-node invasion (LNI) and to perform a meta-analysis to yield pooled area under the receiver operating characteristics curves (AUCs) for model comparison. Materials and methods: An electronic search of the MEDLINE and Embase databases up to October 2016 was undertaken. The AUC value, total number of patients and rate of LNI were extracted from the included references. After excluding redundant literature, 19 studies were identified including 86,338 patients. The Briganti, Partin and MSKCC nomograms were validated in 6629, 69,681 and 10,028 patients, respectively. Results: The pooled AUCs for Briganti, Partin, and MSKCC nomograms were 0.793, 0.778 and 0.780, respectively. The Mantel–Haenszel-derived comparison of AUC values revealed no statistical differences of predictive capabilities for Briganti vs Partin (p = 0.23), Briganti vs MSKCC (p = 0.83) and Partin vs MSKCC (p = 0.26). The accuracy of Briganti, Partin and MSKCC models is statistically similar in predicting the presence of LNI. International guidelines could consider these findings by reporting similarities in the accuracy of these models. Conclusions: The accuracy of Briganti, Partin and MSKCC was similar in predicting the presence of LNI. Based on these results, patients and clinicians may use any of these nomograms without significant advantages.

Detection rate for significant cancer at confirmatory biopsy in men enrolled in Active Surveillance protocol: 20 cores vs 30 cores vs MRI/TRUS fusion prostate biopsy

INTRODUCTION The detection rate for significant prostate cancer of extended vs saturation vs mMRI/TRUS fusion biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol. Mterials and methods: From May 2013 to September 2016 75 men aged 66 years (median) with very low risk PCa were enrolled in an AS protocol and elegible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density < 0.20, 2 < unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core < 50%. All patients underwent 3.0 Tesla pelvic mpMRI before confirmatory transperineal extended (20 cores) or saturation biopsy (SPBx; 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (4 cores) of suspicious lesions (PI-RADS 3-5). RESULTS 21/75 (28%) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI lesions PI-RADS 4-5 vs PI-RADS 3-5 diagnosed 9/21 (42.8%) vs 16/21 (76.2%) significant PCa with 2 false positives (6.5%). The detection rate for significant PCa was equal to 76.2% (mpMRI/TRUS fusion biopsy) vs 81% (extended) vs 100% (SPBx) (p = 0.001); mpMRI/TRUS targeted biopsy and extended biopsy missed 5/21 (23.8%) and 4/21 (19%) significant PCa which were found by SPBx (p = 0.001) being characterised by the presence of a single positive core of GS ≥ 7 with GPC < 10%. CONCLUSIONS Although mpMRI improve the diagnosis of clinically significant PCa, SPBx is provided of the best detection rate for PCa in men enrolled in AS protocols who underwent confirmatory biopsy.

Association Between the Neurogenic Bladder Symptom Score and Urodynamic Examination in Multiple Sclerosis Patients With Lower Urinary Tract Dysfunction.

Purpose: To determine the relationship between the neurogenic bladder symptoms score (NBSS) and urodynamic examination in patients affected by multiple sclerosis (MS) and related lower urinary tract dysfunction (LUTD). Methods: We recruited 122 consecutive patients with MS in remission and LUTD from January 2011 to September 2013 who underwent their first urodynamic examination. Neurological impairment was assessed using the Expanded Disability Status Scale (EDSS) and bladder symptoms were studied with the NBSS. Results: Median NBSS was 20.0 (interquartile range, 12.75–31.0). Neurogenic detrusor overactivity (NDO) was discovered in 69 patients (56.6%). The concordance between patients with NDO and maximum detrusor pressure during involuntary detrusor contraction (PdetmaxIDC)≥20.0 cm H2O was 0.89 (κ-Cohen; P<0.05). Patients with EDSS scores of ≥4.5 had a greater NBSS (25.41 vs. 20.19, P<0.05), NBSS-incontinence (8.73 vs. 4.71, P<0.05), NBSS-consequence (4.51 vs. 3.13, P<0.05) and NBSS-quality of life (2.14 vs. 1.65, P<0.05). The NBSS was not associated with PdetmaxIDC≥20 cm H2O (P=0.77) but with maximum cystometric capacity<212 mL (odds ratio, 0.95; P<0.05). Conclusions: The NBSS cannot give adequate information the way urodynamic studies can, in patients with MS and LUTD.

Tailored treatment including radical prostatectomy and radiation therapy + androgen deprivation therapy versus exclusive radical prostatectomy in high-risk prostate cancer patients: results from a prospective study

PURPOSE To evaluate outcomes of patients with high risk prostate cancer (PCa) who underwent radical prostatectomy (RP) in a context of a multidisciplinary approach including adjuvant radiation (RT) + androgen deprivation therapy (ADT). MATHERIALS AND METHODS 244 consecutive patients with high risk localized PCa underwent RP and bilateral extended pelvic lymph node dissection at our institution. Adjuvant RT + 24 months ADT was carried out in subjects with pathological stage ≥ T3N0 and/or positive surgical margins or in patients with local relapse. RESULTS After a median follow-up was 54.17 months (range 5.4-117.16), 13 (5.3%) subjects had biochemical progression, 21 (8.6%) had clinical progression, 7 (2.9%) died due to prostate cancer and 15 (6.1%) died due to other causes. 136 (55.7%) patients did not receive any adjuvant treatment while 108 (44.3%) received respectively adjuvant or salvage RT+ADT. Multivariate Cox proportional hazard analysis showed that pre-operative PSA value at diagnosis is a significant predictive factor for BCR (HR: 1.04, p < 0.05) and that Gleason Score 8-10 (HR: 2.4; p < 0.05) and PSMs (HR: 2.01; p < 0.01) were significant predictors for clinical progression. Radical prostatectomy group was associated with BPFS, CPFS, CSS and OS at 5-years of 97%, 90%, 95% and 86% respectively, while adjuvant radiation + androgen deprivation therapy group was associated with a BPFS, CPFS and CSS at 5-years of 91%, 83%, 95% and 88%, without any statistical difference. CONCLUSIONS Multimodality tailored treatment based on RP and adjuvant therapy with RT+ADT achieve similar results in terms of OS after 5-years of follow-up.