Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Fluctuation in prostate cancer gene 3 (PCA3) score in men undergoing first or repeat prostate biopsies.

OBJECTIVE: To evaluate the variability in prostate cancer gene 3 (PCA3) score over time in men with elevated serum prostate-specific antigen (PSA) levels who are undergoing first or repeat prostate biopsy. PATIENTS AND METHODS: A total of 360 men from two Italian institutions who had undergone at least two PCA3 assessments were selected. Of these, 97.5% were scheduled for first or repeat prostate biopsy because of elevated PSA level and/or positive digital rectal examination (DRE). We compared the PCA3 scores in men with a negative biopsy (normal parenchyma, benign prostatic hyperplasia [BPH], chronic prostatitis, high-grade prostate intraepithelial neoplasia [HG-PIN]) with those in men with a positive biopsy. We evaluated PCA3 repeated measures biological variability and its possible association with basic patient characteristics (age, family history of prostate cancer, DRE, prostate volume, BPH, prostatitis and HG-PIN). Three different thresholds were used to evaluate the possible changes in risk class: the standard threshold (a PCA3 score of 35), a US Food and Drug Administation-approved PCA3 threshold of 25 and a threshold selected based on our previous research which was a PCA3 score of 50. RESULTS: The PCA3 scores varied significantly (P < 0.001) when comparing men with a negative biopsy with those with a positive biopsy (median [range] PCA3 score: 25 [2-276] vs 43 [7-331]). There was no significant difference in PCA3 scores in men with chronic prostatitis and HG-PIN compared with other men with negative biopsies. The median (range) time between the two PCA3 assessments was 16.2 (3-53.7) months. No association was found between PCA3 repeated measures modifications and age, family history of prostate cancer, DRE, BPH, prostatitis, HG-PIN and use of 5-α-reductase inhibitors. The variability of PCA3 scores on repeated measures confirmed the risk class for about 80% of patients; of the remaining 20% of patients, the risk class was upgraded in two thirds and downgraded in one third. CONCLUSION: PCA3 score can be considered a stable marker over time in most cases but there is a group of men among whom there is clinically notable risk class change. Further investigation is required to determine the genesis of this phenomenon.

Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy.

PURPOSE: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

Histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia do not influence urinary prostate cancer gene 3 score.

UNLABELLED: What's known on the subject? and What does the study add? While the relationship between PCA3 score and clinical or histological prostatitis was quite proven even in small patient groups, conversely the relationship between PCA3 score and HG-PIN is still under debate. We demonstrated in a large series (432 patients) that histologically documented chronic prostatitis and HG-PIN have similar PCA3 scores to patients with BPH and/or normal parenchyma at biopsy. OBJECTIVE: To determine whether histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia (HG-PIN) influence the prostate cancer gene 3 (PCA3) score in Italian patients with an elevated prostate-specific antigen (PSA) level and a negative digital rectal examination (DRE) who were undergoing a first or repeat prostate biopsy. PATIENTS AND METHODS: A urinary PCA3 test was prospectively performed in 432 consecutive patients who were admitted to Gradenigo Hospital (Turin, Italy) between January and December 2011 and scheduled for first or repeat prostate biopsy as a result of an elevated PSA level and negative DRE. A comparison of the PCA3 score and patients with a negative biopsy (normal parenchyma, benign prostatic hyperplasia, chronic prostatitis, HG-PIN) or positive biopsy was performed. RESULTS: PCA3 median (range) scores varied significantly (P < 0.001) in men with a negative vs positive biopsy: 33 (2-212) and 66 (5-324), respectively. By contrast, men with chronic prostatitis and HG-PIN showed no significant difference with respect to PCA3 score compared to other negative biopsy patients. No correlation was found between the number of positive cores for chronic prostatitis, HG-PIN and PCA3 score. Of all patients with a positive biopsy, 23 (20%) of 114 men had a PCA3 score ≤ 35. In total, 79 (40%) of 197 men with a negative biopsy (normal parenchyma and benign prostatic hyperplasia), 24 (37.5%) of 64 men with chronic prostatitis and 19 (39.6%) of 48 men with HG-PIN had a PCA3 score >35. CONCLUSION: At this early stage of clinical evaluation, cancer specificity of the urinary PCA3 test appears to be maintained in the face of chronic prostatitis and HG-PIN.

[Benign prostate hypertrophy and sexual health]. / Hyperplasie prostatique bénigne et santé sexuelle.

This article is centered on the possible impact of benign prostate hypertrophy on the male sexual life. Not only concerning the symptomatology of this affection but also concerning the side-effects of medication as well as, if necessary, a surgical intervention. A particular attention is given to the possibility of using new associations between medication, for instance between alpha-blockers and inhibitors of 5-phosphodiesterases.

Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.

Pathological patterns of prostate biopsy in men with fluctuations of prostate cancer gene 3 score: a preliminary report.

BACKGROUND: To evaluate pathological patterns of prostate biopsy in men with changes in risk class by prostate cancer gene 3 (PCA3) score and with elevated serum prostate-specific antigen (PSA) or positive digital rectal examination (DRE), undergoing a repeat biopsy. PATIENTS AND METHODS: A total of 108 males of two Italian Institutions who had undergone at least two PCA3 score assessments with changed PCA3 risk class were selected. Comparison of PCA3 score in patients with negative re-biopsy [normal parenchyma, benign prostatic hyperplasia (BPH), chronic prostatitis, high-grade prostate intraepithelial neoplasia (HG-PIN), atypical small acinar prostate (ASAP)] or positive re-biopsy was performed. RESULTS: The up- and down-grading rates for PCA3 score were 71.3% (n=77) and 28.7% (n=31), respectively. Among the 77 up-graded patients, the median change in PCA3 score was 24 (range=4-69), while among the 31 down-graded ones, the median change was 17 (2 to 55). The PCA3 score in 24 out of 29 (82.7%) patients with prostate cancer (PCa) was up-graded. No association was found for correlation of PCA3 score change with age >65 years (p=0.975), family history of prostate cancer (p=0.796), positive DRE (p=0.179), use of 5-alpha-reductase inhibitors (p=0.793) and BPH/prostatitis/HG-PIN/ASAP diagnosis (p=0.428). CONCLUSION: PCA3 score can be considered a marker that is stable over time in most cases; notably, up to 20% of patients have a clinically relevant change of risk class. The rate of PCa was higher in patients whose PCA3 score was up-graded, even if no robust cut-off for PCA3 score fluctuation was identified.

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

OBJECTIVE: To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). PATIENTS AND METHODS: In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). RESULTS: Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. CONCLUSION: In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

AIM: To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). PATIENTS AND METHODS: in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). RESULTS: The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). CONCLUSION: The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN.

Biopsy and radical prostatectomy pathological patterns influence Prostate cancer gene 3 (PCA3) score.

AIM: To evaluate the relationship between Prostate cancer gene 3 (PCA3) score and prostate cancer as assessed by Gleason Score (GS) and pathological stage in a series of Italian patients, with elevated Prostate specific antigen (PSA) undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A total of 222 patients underwent RP for clinically localized prostate cancer; total PSA, free-PSA (%fPSA) and PCA3 score were collected and the possible associations among PCA3 and histological grade/pathological stage at biopsy and RP were investigated. RESULTS: Median PCA3 scores by GS at radical prostatectomy were 51 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), while scores at the biopsy were 56 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), and in pT2 vs. pT3 patients they were 54 vs. 80 (p=0.001). Positive digital rectal examination (DRE) (odds ratio (OR)=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main risk factors for the presence of an aggressive disease (GS ≥ 7 at RP). CONCLUSION: PCA3 score could play an interesting role in predicting significant disease: positive DRE (OR=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main independent risk factors for GS ≥ 7 at RP.

Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer: a validation study on an Italian patient population undergoing first and repeat biopsy.

OBJECTIVE: To determine an optimal prostate cancer gene 3 (PCA3) cutoff in predicting prostate cancer in Italian patients undergoing first or repeat biopsy. STUDY DESIGN: In this observational multicenter study 1246 men with elevated prostate specific antigen (PSA) and negative digital rectal examination, with prostate biopsy after PCA3 assessment, were divided into two groups submitted to PCA3 testing before or after previous negative biopsies. Ideal PCA3 cutoff was identified using area under the curve of the receiver operating characteristic analysis. Various cutoff values were used to determine the best predictive score. Univariate and multivariate logistic regression models compared age, PSA, free-PSA, and PCA3 score to predict prostate cancer. RESULTS: PCA3 cutoff 39-50 had the highest accuracy in the repeat biopsy group in which cutoff of 39 could have avoided 51.9% negative repeat biopsies, eventually missing 7.8% of cancers (all low risk); cutoff of 50 would have prevented 56.5% of negative repeat biopsies, missing 29 tumors (10.3%), 5 potentially aggressive. The PCA3 test performed poorly in the first biopsy group. CONCLUSION: We confirm the usefulness of PCA3 in Italian men with a previous negative biopsy. We achieved the best performance at a cutoff of 39. PCA3 did not perform better than PSA in non-biopsy-selected men.

Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies.

Exposure to 4-aminobiphenyl (4-ABP) is an important determinant of urinary bladder cancer in humans. We have analyzed by gas chromatography-mass spectrometry the DNA adducts of 4-ABP in 75 bladder cancer biopsies. The purpose was to understand whether smoking, N-acetyltransferase 2 (NAT2) polymorphism, diet or tumor grade were determinants of 4-ABP-DNA levels. 4-ABP-DNA adducts were above the detection limit of 0.1 fmol/microg DNA for 37/75 patients. Overall the level of adducts was 2.7 +/- 0.7 (mean +/- SE) fmol/microg DNA (86 +/- 22 adducts/10(8) normal nucleotides, mean +/- SE). A strong association with grade was observed. In the group of patients with detectable 4-ABP-DNA adducts the odds ratio for having a tumor grade of 2 or 3 was respectively 4.3 (95% CI 0.8-21.9) and 6 (1.3-27.5), compared with grade 1. A non-statistically significant association was found between adduct levels and the deduced slow acetylator phenotype in grades 2 and 3. The intake of fruit and vegetables produced a lower frequency of detectable adducts, though the association was not statistically significant. Detectable 4-ABP-DNA adducts were clearly associated with current smoking in higher tumor grades (grade 3 versus grades 1 + 2, odds ratios 10.4; 95% CI 1.7-63.1). Overall, our findings indicate that higher levels of DNA adducts characterize more invasive tumors (higher tumor grades). This seems to be facilitated by smoking and contrasted by the intake of fruit and vegetables.