Fabiana Cancrini

Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis.

To assess the association between physical activity, evaluated by the Physical Activity Scale for the Elderly (PASE) questionnaire, and prostate cancer risk in a consecutive series of men undergoing prostate biopsy.

Serum levels of chromogranin A are not predictive of high-grade, poorly differentiated prostate cancer: results from an Italian biopsy cohort.

OBJECTIVES To explore the association of chromogranin A (CgA) levels and the risk of poorly differentiated prostate cancer (CaP) in men undergoing prostate biopsy. MATERIALS AND METHODS Between 2006 and 2012, we prospectively enrolled 1,018 men with no history of CaP undergoing prostate biopsy. The risk of detecting poorly differentiated CaP as a function of CgA concentration was evaluated using crude and adjusted logistic regressions. Further analyses were performed to determine whether CgA was a significant predictor of high-grade CaP in men with low PSA (<10 ng/ml). RESULTS We found a significantly higher level of CgA in men with poorly differentiated CaP. CgA was however co-linear with age, and serum CgA levels were not significantly associated with the overall risk of CaP, and the specific risk of poorly differentiated CaP (OR 1.001 95% CI 0.99-1.01, P = 0.74). Moreover, in men with low PSA levels (<10 ng/ml), CgA was not a significant predictor of high grade-disease on univariate (OR 1.00; 95% CI 0.99-1.01; P = 0.66) and multivariate analysis (P = 0.85). CONCLUSIONS In our cohort of patients, the serum level of CgA is not a significant predictor of poorly differentiated CaP on initial prostate biopsy, even in men with low PSA levels (<10 ng/ml). According to our experience, CgA should not be considered a reliable marker to predict poorly differentiate cancer in the setting of initial prostate biopsy.

Contribution of Genome-Wide Association Studies to Scientific Research: A Pragmatic Approach to Evaluate Their Impact

The factual value of genome-wide association studies (GWAS) for the understanding of multifactorial diseases is a matter of intense debate. Practical consequences for the development of more effective therapies do not seem to be around the corner. Here we propose a pragmatic and objective evaluation of how much new biology is arising from these studies, with particular attention to the information that can help prioritize therapeutic targets. We chose multiple sclerosis (MS) as a paradigm disease and assumed that, in pre-GWAS candidate-gene studies, the knowledge behind the choice of each gene reflected the understanding of the disease prior to the advent of GWAS. Importantly, this knowledge was based mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway-oriented comparisons of old and new knowledge in MS by confronting an unbiased list of candidate genes in pre-GWAS association studies with those genes exceeding the genome-wide significance threshold in GWAS published from 2007 on. At the single gene level, the majority (94 out of 125) of GWAS-discovered variants had never been contemplated as plausible candidates in pre-GWAS association studies. The 31 genes that were present in both pre- and post-GWAS lists may be of particular interest in that they represent disease-associated variants whose pathogenetic relevance is supported at the phenotypic level (i.e. the phenotypic information that steered their selection as candidate genes in pre-GWAS association studies). As such they represent attractive therapeutic targets. Interestingly, our analysis shows that some of these variants are targets of pharmacologically active compounds, including drugs that are already registered for human use. Compared with the above single-gene analysis, at the pathway level GWAS results appear more coherent with previous knowledge, reinforcing some of the current views on MS pathogenesis and related therapeutic research. This study presents a pragmatic approach that helps interpret and exploit GWAS knowledge.

Serum levels of 17-β-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort

OBJECTIVES To explore the association between serum levels of 17-β-estradiol (17BE) and prostate cancer (PCa) risk in men undergoing prostate biopsy. METHODS AND MATERIALS Between 2006 and 2012, we prospectively enrolled 894 patients, with no history of PCa, undergoing prostate biopsy. Before biopsy was performed, general data, digital rectal examination (DRE), body mass index, 17BE, and prostate-specific antigen (PSA) were recorded. The risk of detecting cancer and high-grade cancer was assessed as a function of 17BE using crude and adjusted logistic regressions. RESULTS Serum levels of 17BE were not associated with an increased risk of PCa or high-grade disease. Age (odds ratio [OR] 1.05; 95% confidence interval [CI]: 1.03-1.07; P = 0.000), DRE(OR 2.81; 95% CI: 1.98-4.00; P = 0.000), and PSA(OR 1.07; 95% CI: 1.04-1.10; P = 0.000) were found to be independent predictors of PCa risk. Age (OR 1.05; 95% CI: 1.01-1.09; P = 0.007), DRE (OR 3.04; 95% CI: 1.79-5.17; P = 0.000), body mass index (OR 1.07; 95% CI: 1.01-1.150; P = 0.040), and PSA (OR 1.08; 95% CI: 1.03-1.12; P = 0.000) were found to be independent predictors of high-grade disease. CONCLUSION In our cohort of patients, serum levels of 17BE are not predictive of PCa or high-grade disease. In patients at risk of PCa, 17BE should not be considered a reliable marker to predict poorly differentiated PCa in the setting of initial prostate biopsy.

MP13-06 PHARMACOLOGICAL TREATMENT OF LOWER URINARY TRACT SYMPTOMS AFTER A TRANSURETHRAL RESECTION OF THE PROSTATE IS PREDICTIVE OF A NEW SURGICAL TREATMENT: 10 YEARS FOLLOW-UP

INTRODUCTION AND OBJECTIVES: To evaluate the longterm (at least 10 years) characteristics of patients with persistent LUTS after a TURP and continue their medical therapy post-operatively. METHODS: A consecutive series of patients with LUTS and Benign prostatic enlargement (BPE) underwent TURP in our center in 2004-2005 and they were then followed up to 2016. Patients were assessed at baseline, 3-, 6months post-operatively and yearly thereafter with medical history (concomitant medication, reintervention), IPSS, PSA, prostate volume, maximal urinary flow rate (Qmax), post void residual urine (PVR). Reoperation was defined as the requirement of a new TURP to relieve bothersome LUTS. Multivariate logistic regression was used to determine covariates associated with reoperation rate and the Kaplan-Meier curve assessed the time to reoperation. RESULTS: Overall 92 patients were enrolled. Mean age was 79 7 years; mean PSA was 3.2 2.5 ng/ml; mean TRUS volume was 57.5 18.6 ml; mean Qmax was 8.7 4 ml/s; mean IPPS was 23 6 respectively at baseline. Mean follow-up was 140 8 months (median 142 months). Overall 20/92 (21.7%) patients received medical treatment (alpha-blockers and/or 5 alpha-reductase inhibitors) after TURP. 13 patients underwent re-TURP during follow-up (reoperation rate was 14%); out of them 9/13 (69%) received medical treatment for persistent LUTS, while the remaining 4 patients received no additional pharmacological treatment (p1⁄4 0.001). Out of the 13 patients treatedwith re-TURP, 12 (92%) underwent surgery within 5 years of follow-up. Median time to reintervention was 26 months, interquartile range 14/46. The need of LUTS/BPE pharmacological treatment after TURP is an independent risk factor for re-intervention (Odds Ratio 13.93; 95% Confidence Interval 3.63-53.48, p1⁄4 0.000). Cumulative re-TURP free probability, according to post-operative continuing medical treatment, is showed in Figure 1. CONCLUSIONS: In our study, a small number of patients (21.7%) still required pharmacological treatment for persistent LUTS. This need was a predictive factor of a re-TURP. Considering that more that 90% of re-TURP were performed during the first 5 years of followup, it is assumable that a follow-up longer than 5 years is not needed in such group of patients.

Analysis of the relationship between benign prostatic hyperplasia/lower urinary tract symptoms and total serum testosterone level

Study design, materials and methods From 2009 onwards, a consecutive series of patients with LUTS related to BPE were prospectively enrolled. Patients were evaluated using the International prostatic symptom score (IPSS), ultrasound prostate volume assessment. Body mass index (BMI) as well as waist circumferences were measured. Blood samples were collected and tested for: PSA levels, testosterone, Sex Hormone Binding Globuline (SHBG), 17-Beta estradiol. We evaluated the association between hormone serum levels and LUTS/BPE using logistic regression analyses and Spearman correlation test.