Simone Albisinni

Abdominal obesity as risk factor for prostate cancer diagnosis and high grade disease: A prospective multicenter Italian cohort study

OBJECTIVE To evaluate the association between abdominal obesity and prostate cancer (CaP) diagnosis and grade in patients undergoing prostate biopsy. MATERIALS AND METHODS Between 2008 and 2011, we prospectively enrolled patients referred to 3 clinics in Italy who were scheduled for transrectal ultrasound (TRUS) guided prostate biopsy. Before biopsy, digital rectal examination (DRE), prostate specific antigen (PSA), body mass index (BMI), and waist circumference (WC) were measured. Men were categorized in 4 groups of body habitus, according to BMI and waist circumference values. Crude and adjusted logistic regressions were performed to assess the association of BMI (continuous), waist circumference (continuous), body habitus (categorical), and CaP diagnosis and grade. RESULTS Six hundred sixty-eight patients were enrolled. CaP was detected in 246 patients (38%), of whom 136 had low-grade (Gleason score ≤ 6) and 110 high-grade cancer (Gleason score ≥ 7). Logistic regression multivariate analysis showed that BMI (OR 1.05 per unit, CI 95% 1.00-1.10 P = 0.033) and waist circumference (OR 1.02 per cm, CI 95% 1.00-1.04 P = 0.026) were significant predictors of CaP diagnosis. BMI (OR 1.11 95% CI 1.04-1.18 P = 0.001) and WC (OR 1.04 95% CI 1.02-1.06 P = 0.001) were also associated with high-grade CaP. Furthermore, obesity with central adiposity (BMI ≥ 30 kg/m(2) and WC ≥ 102 cm) was significantly associated with CaP diagnosis (OR 1.66, CI 95% 1.05-2.63, P = 0.03) and high-grade disease (OR 2.56, CI 95% 1.38-4.76, P = 0.003). CONCLUSIONS Obesity defined by BMI and WC seems to be associated with CaP and, more specifically, with high-grade disease at the time of biopsy. The relationship between obesity and CaP is complex and remains to be further addressed.

Predictive value of digital rectal examination for prostate cancer detection is modified by obesity.

The American Cancer Societys updated screening guidelines for prostate cancer (CaP) render digital rectal examination (DRE) optional. We investigated the impact of DRE on CaP detection among obese men. Data from 2794 men undergoing initial prostate biopsy at three centers were analyzed to assess CaP risk attributed to abnormal DRE across body mass index (BMI) categories. Predictive accuracies of a combination of PSA, age, race, center and biopsy year including or excluding DRE findings were compared by areas under the receiver-operating characteristics curves. In all cohorts, obese men were less likely to have abnormal DREs diagnosed than non-obese men. As BMI category increased, abnormal DREs became stronger predictors for overall CaP in individual (P-trends⩽0.05) and combined (P-trend<0.001) cohorts, and for high-grade CaP in the Italian (P-trend=0.03) and combined (P-trend=0.03) cohorts. DRE inclusion improved the predictive accuracy for overall and high-grade CaP detection among all obese men (P⩽0.032) but not normal-weight men (P⩾0.198). DRE inclusion also near-significantly improved overall CaP detection in obese men with PSA<4 ng ml–1 (P=0.081). In conclusion, the predictive value of DRE is dependent on obesity and is significantly higher among obese men than normal-weight men.

Greater Percent-free Testosterone Is Associated With High-grade Prostate Cancer in Men Undergoing Prostate Biopsy

OBJECTIVE To analyze the serum androgen concentrations in men who underwent an initial prostate biopsy, focusing on the percent-free testosterone (%FT) as a predictor of low- and high-grade prostate cancer (PCa). Most studies have suggested that the absolute serum testosterone and free testosterone levels are not related to PCa risk. However, to date, the concurrent effect of free and total testosterone levels has not been evaluated. In particular, the association of the %FT (free testosterone/total testosterone) with PCa risk has not been explored. METHODS From 2006 to 2010, we collected data on 812 white Italian men with no history of PCa who underwent 12-core biopsy. The testosterone, free testosterone, and %FT (free testosterone/total testosterone) were examined as predictors of low-grade (Gleason score of ≤ 6) and high-grade (Gleason score ≥ 7) PCa using crude and adjusted multinomial logistic regression analysis. RESULTS On multivariate analysis, testosterone (P ≥ .11) and free testosterone (P ≥ .45) were not significantly associated with low- or high-grade PCa. A greater %FT level significantly predicted high-grade PCa on both crude (P = .01) and multivariate (P = .02) analysis but not low-grade PCa (P ≥ .38). When examined in tertiles, men in the greatest %FT tertile had a significant twofold increased risk of high-grade PCa (odds ratio 2.04, 95% confidence interval 1.23-3.37, P = .005). CONCLUSION In white Italian men, a greater %FT level was associated with an increased risk of high-grade PCa on initial prostate biopsy. These findings suggest that a high %FT level, rather than the absolute androgen levels, might be associated with high-grade PCa. Additional studies are needed to confirm our findings.

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.

The Role of Inflammation in the Progression of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is the most frequent urological occurrence in elderly males, and recently prostatic inflammation has been involved in the pathogenesis and progression of the disease. Inflammatory infiltrates determine cytokine release in the prostatic microenvironment, with consequent tissue damage and subsequent chronic tissue healing that results in the development of BPH. Clinical trials have reported an association between prostatic inflammation and the risk of BPH progression. Moreover, men with metabolic syndrome appear to be at increased risk of BPH, probably for the concomitance of systemic inflammation associated with such syndrome. Understanding the immune pathways associated with BPH will aid in identifying novel therapeutic targets and improve the management of the disorder. The aim of this review is to evaluate the available evidence on the role of prostatic inflammation on BPH and its progression and to discuss the possible clinical implications.

Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: A 12 months analysis after three consecutive prostate biopsies

PURPOSE To evaluate the risk of prostate cancer (PCa) on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN). MATERIALS AND METHODS From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE) were scheduled for trans-rectal ultrasound (TRUS) guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. RESULTS A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22%) men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34%) still showed HGPIN, 15 (35%) were diagnosed with PCa and 9 (21%) presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04). Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. CONCLUSIONS Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.