Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample

PURPOSE: The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. METHODS: A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. RESULTS: A total of 392 men (65.4 +/- 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 +/- 0.1 ng/ml) than in those with the CC-genotype (1.7 +/- 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 +/- 2.0 vs. 32 +/- 0.8 ml, P = 0.02) and lower PSA levels (1.6 +/- 0.3 vs. 1.9 +/- 0.1 ng/ml). CONCLUSIONS: The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameter

The Long-Term Effect of Radical Prostatectomy on Erectile Function, Urinary Continence, and Lower Urinary Tract Symptoms: A Comparison to Age-Matched Healthy Controls

Introduction. To analyze the impact of radical prostatectomy (RPE) on erectile function and lower urinary tract function in comparison to age-matched healthy men. Materials and Methods. Patients who underwent radical retropubic prostatectomy completed questionnaires containing the IIEF-5, the Bristol female LUTS questionnaire, and the International Prostate Symptom Score (IPSS). Results. Patients after RPE were included (n=363). Age-matched healthy men (n=363) were included. The mean IIEF-5 of patients aged 61–70 yrs after RPE was 10.4±6.6 versus 18.8±5.3 in the control cohort; the respective values for men aged 71–80 yrs after RPE were 7.2±6.5 versus 13.6±7.7 in the control cohort. Urinary incontinence after RPE was reported in 41.9% (61–70 years) and 37.7% (71–80) versus 7.5% and 15.1% in the control cohort. The mean IPSS of patients after RPE aged 61–70 yrs was 5.0±4.4 versus 5.5±4.9 in the control cohort; the respective values for men aged 71–80 yrs were 6.0±4.9 versus 7.5±5.7 in the healthy cohort. Conclusions. The negative effect of radical prostatectomy on erectile and urinary incontinence remains substantial. The physiologically declining erectile and lower urinary tract function with ageing reduces the difference between healthy men and those after surgery. Healthy men have a higher IPSS presumably due to the presence of bladder outlet obstruction

The influence of family history on prostate cancer risk: implications for clinical management

A family history of prostate cancer has long been identified as an important risk factor for developing the disease. This risk factor can be easily assessed in clinical practice and current guidelines recommend to initiate prostate cancer early detection 5 years earlier (i.e. around the age of 40 years) than in men without a positive family history. This review elucidates the close association between the proximity of relatedness, greater number of affected family members and earlier age at diagnosis of the family members and prostate cancer risk. The evidence for prostate cancer risk reduction by 5 alpha-reductase inhibitors has potential to expand management options for men at high risk for developing prostate cancer beyond more frequent and/or earlier surveillance. center dot The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. center dot Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. center dot These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5 alpha-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. center dot Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment

The influence of family history on prostate cancer risk: implications for clinical management.

A family history of prostate cancer has long been identified as an important risk factor for developing the disease. This risk factor can be easily assessed in clinical practice and current guidelines recommend to initiate prostate cancer early detection 5 years earlier (i.e. around the age of 40 years) than in men without a positive family history. This review elucidates the close association between the proximity of relatedness, greater number of affected family members and earlier age at diagnosis of the family members and prostate cancer risk. The evidence for prostate cancer risk reduction by 5 alpha-reductase inhibitors has potential to expand management options for men at high risk for developing prostate cancer beyond more frequent and/or earlier surveillance. center dot The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. center dot Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. center dot These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5 alpha-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. center dot Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment

High BMI, Aggressive Tumours and Long Console Time Are Independent Predictive Factors for Symptomatic Lymphocele Formation after Robot-Assisted Radical Prostatectomy and Pelvic Lymph Node Dissection

Introduction: Lymphocele (LC) formation is a common complication which may cause severe symptoms after robot-assisted radical prostatovesiculectomy (RARP) with concomitant pelvic lymph node dissection (PLND). Compared to open radical prostatectomy, the amount of data on potential risk factors for LC formation is still limited. The aim of the present study was to identify risk factors for symptomatic LC formation (sLC) after RARP with PLND. Methods: We used the data of a prospective multicentre series of 232 RARP patients which were treated between March 2017 and December 2017. The primary endpoint was the presence of sLC within 90 days. Asymptomatic LC (aLC) formation was also recorded. We evaluated clinical, perioperative, and histopathological criteria and compared their distribution in patients with and without post-operative sLC. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify potential predictors for LC formation. Regarding the influence of patients’ BMI, 2 models were calculated: BMI continuously (model 1) and BMI dichotomized with cut-off 30 kg/m2 (WHO definition, model 2). Results: Post-operative sLC was present in 21 patients (9.1%), while aLC was detected in 49 patients (21.1%) 90 days after RARP with PLND. Patients with sLC showed higher median baseline PSA levels (9.8 vs. 8.1 ng/mL), higher prevalence of obesity (BMI >30; 42.9 vs. 19.9%), and longer median console time (180 vs. 165 min) compared to patients without sLC. On MVA higher BMI {model 1: OR 1.145 (confidence interval [CI] 1.025–1.278); model 2: OR 2.761 (1.045–7.296)}, longer console time (model 1: OR 1.013 [1.005–1.021]; model 2: OR 1.013 [1.005–1.020]) and an ISUP grade ≥3 (model 1: OR 3.247 [1.182–8.917]; model 2: OR 2.791 [1.050–7.423]) were identified as independent predictors for sLC development. Conclusion: Patients with aggressive tumours and higher BMI should be informed about a potentially increased risk for sLC formation. In case of a long console time, a close and regular follow-up should be considered to check for LC development

Peritoneal Flap in Robot-Assisted Radical Prostatectomy

Background: Lymphocele is the most common complication arising after pelvic lymph node dissection (PLND) in the setting of robot-assisted radical prostatectomy (RARP). The only data available until now on the utility of a peritoneal flap to prevent lymphocele were retrospectively acquired. Methods: A randomized, controlled, multi-center trial with blinded assessment of endpoints was carried out on 232 patients with prostate cancer who underwent RARP with PLND. The patients in the intervention group were given a peritoneal flap; in the control group, surgery was performed without this modification. The two joint primary endpoints were the rates of symptomatic lymphocele during the same hospitalization as the operative procedure (iT1) and within 90 days of surgery (iT2). The secondary endpoints were lymphocele volume, the need for treatment of lymphocele, complications requiring an intervention, and the degree of postoperative stress incontinence. German Clinical Trials Register number: DRKS00011115. Results: The data were evaluated in an intention-to-treat analysis, which, in this trial, was identical to an as-treated analysis. 108 patients (46.6%) were allotted to the intervention group. There were no statistically significant intergroup differences with respect to any clinical or histopathological criteria. A median of 16 lymph nodes were removed (interquartile range, 11-21). A symptomatic lymphocele arose in 1.3% (iT1) and 9.1% (iT2) of the patients, without any statistically significant difference between the two trial groups (p = 0.599 and p = 0.820, respectively). Nor did the groups differ significantly with respect to lymphocele volume (p = 0.670 on hospital discharge [T1], p = 0.650 90 days after surgery [T2]) or the type and frequency of need for subsequent surgical intervention (p = 0.535; iT2). 81.5% of all patients (n = 189) had no complications at all in the first three months after surgery. Nor were there any intergroup differences at 90 days with respect to the degree of stress urinary incontinence (p = 0.306) or complications (p = 0.486). Conclusion: A peritoneal flap after RARP was not found to influence the rate of postoperative lymphocele, whether asymptomatic or requiring treatment