Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia.

OBJECTIVE: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA). METHODS: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis. RESULTS: Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3-3.3 µM], P <.01) and the PIN (1.9 µM [1.2-6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6-1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH. CONCLUSION: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.

Hyperglycemia and T Cell infiltration are associated with stromal and epithelial prostatic hyperplasia in the nonobese diabetic mouse.

BACKGROUND: Prostatic inflammation and various proinflammatory systemic comorbidities, such as diabetes and obesity are associated with human benign prostatic hyperplasia (BPH). There is a paucity of in vivo models reflecting specific aspects of BPH pathogenesis. Our aim was to investigate the nonobese diabetic (NOD) mouse as a potential model for subsequent intervention studies. MATERIALS AND METHODS: We used the NOD mouse, a model of autoimmune inflammation leading to type 1 diabetes to examine the effects of systemic inflammation and diabetes on the prostate. We assessed changes in prostatic histology, infiltrating leukocytes, and gene expression associated with aging and diabetic status. RESULTS: Both stromal expansion and epithelial hyperplasia were observed in the prostates. Regardless of diabetic status, the degree of prostatic hyperplasia varied. Local inflammation was associated with a more severe prostatic phenotype in both diabetic and nondiabetic mice. Testicular atrophy was noted in diabetic mice, but prostate glands showed persistent focal cell proliferation. In addition, a prostatic intraepithelial neoplasia (PIN)-like phenotype was seen in several diabetic animals with an associated increase in c-Myc and MMP-2 expression. To examine changes in gene and cytokine expression we performed microarray and cytokine array analysis comparing the prostates of diabetic and nondiabetic animals. Microarray analysis revealed several differentially expressed genes including CCL3, CCL12, and TNFS10. Cytokine array analysis revealed increased expression of cytokines and proteases such as LDLR, IL28 A/B, and MMP-2 in diabetic mice. CONCLUSION: Overall, NOD mice provide a model to examine the effects of hyperglycemia and chronic inflammation on the prostate, demonstrating relevance to some of the mechanisms present underlying BPH and potentially the initiation of prostate cancer.

Statin use linked with a decrease in the conversion from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer.

The roles of obesity, metabolic dysregulation and systemic inflammation to advance prostate carcinogenesis are unclear. This study investigates metabolic and inflammatory factors in the transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). We prospectively followed 160 men diagnosed with HGPIN at biopsy and therefore at high-risk and clinically monitored for PC. Analyses investigated body mass index (BMI), waist circumference, waist-hip ratio (WHR), height, fat mass, lean mass percent body fat, NSAIDs, statins, metformin, diabetes, hypertension, hypercholesterolemia representing metabolic dysregulation on the risk of a PC diagnosis during follow-up. Systemic inflammation was estimated through measurement of 13 plasma cytokine levels. Statin use was significantly linked with overall PC at follow-up [odds ratio (OR) = 0.45, (0.23, 0.91), P = 0.03], with a somewhat stronger link with high-grade [OR = 0.39, (0.15, 1.04), P = 0.06] PC compared with low-grade PC [OR = 0.50, (0.23, 1.12), P = 0.09]. Non-statin cholesterol-lowering medications, BMI, WHR, diabetes, hypertension and percent body fat were not significantly associated with PC. Although blood IL-12p70, IL-2 and IL-1ß levels were significantly lower among statin users, inflammatory markers were not significantly linked with PC and did not explain the observed relationship between statins and lower PC risk. In summary, this prospective study of HGPIN patients at high risk for PC finds that statin use was significantly associated with reduced risk of PC detection at follow-up. Systemic markers of inflammation did not mediate this association, suggesting that statins affect PC progression through alternative pathways.

Pretreatment Serum Cystatin C Levels Predict Renal Function, but Not Tumor Characteristics, in Patients with Prostate Neoplasia.

To evaluate the role of Cystatin C (Cys-C) in tumorigenesis and progression of prostate cancer (PCa), we retrospectively collected the clinical information from the records of 492 benign prostatic hyperplasia (BPH), 48 prostatic intraepithelial neoplasia (PIN), and 173 PCa patients, whose disease was newly diagnosed and histologically confirmed. Pretreatment serum Cys-C levels were compared across the various groups and then analyzed to identify relationships, if any, with clinical and pathological characteristics of the PCa patient group. There were no significant differences in serum Cys-C levels among the three groups (P > 0.05). In PCa patients with normal SCr levels, patient age was correlated with serum Cys-C level (P ≤ 0.001) but did not correlate with alkaline phosphatase (AKP), lactate dehydrogenase (LDH), prostate specific antigen (PSA), Gleason score, or bone metastasis status (P > 0.05). Age and SCr contributed in part to the variations in serum Cys-C levels of PCa patients (r = 0.356, P ≤ 0.001; r = 0.520, P ≤ 0.001). In conclusion, serum Cys-C levels predict renal function in patients with prostate neoplasia, but were not a biomarker for the development of prostate neoplasia, and were not correlated with the clinicopathological characteristics of PCa.

"Finding the needle in a haystack": oncologic evaluation of patients treated for LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral resection of the prostate (TURP).

PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy, resected prostate weight, and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP, respectively, the choice of procedure had no influence on the detection of iPCa (p = 0.593). However, a higher rate of false-negative preoperative prostate biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007). In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI 1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as independent predictors for the detection of iPCa. CONCLUSIONS: Despite differences in oncologic parameters, the choice of technique had no influence on the detection of iPCa. Increased patient age and higher PSA density were associated with iPCa. A higher rate of false-negative preoperative prostate biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS patients requires a more adapted approach to exclude malignancy, especially in those with larger prostates.

Promoter methylation of MCAM, ERα and ERß in serum of early stage prostate cancer patients.

BACKGROUND: Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.8 % and specificity is 41.1%. As a result, the serum PSA test leads to numerous unneeded biopsies. Therefore, a rigorous search for biomarkers for early detection of PC is ongoing. In this study, we aim to assess a panel of epigenetic markers in an intend to develop an early detection test for PC. RESULTS: The sensitivity and specificity of hypermethylation of MCAM was 66% and 73% respectively which is an improvement from the sensitivity and specificity of PSA. Considering a combination marker panel of MCAM, ERα and ERß increased the sensitivity to 75% and the specificity became 70% for the minimally invasive early detection test of PC. MATERIALS AND METHODS: Sixteen primary matched tumor and serum were analyzed by quantitative methylation specific PCR (QMSP) to determine analytical and clinical sensitivity of the genes tested (SSBP2, MCAM, ERα, ERß, APC, CCND2, MGMT, GSTP1, p16 and RARß2). Additionally, serum samples from eighty four cases of PC, thirty controls and seven cases diagnosed as high grade Prostatic Intraepithelial Neoplasia (HGPIN) were analyzed. CONCLUSIONS: Promoter methylation of MCAM, ERα and ERß have a potential to be utilized as biomarker for the early detection of prostate PC as their sensitivity and specificity seem to be better than serum PSA in our cohort of samples. After robust validation in a larger prospective cohort, our findings may reduce the numbers of unwarranted prostate biopsies.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result

Abstract Introduction: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a positive second biopsy in males considered for re-biopsy. Material and Methods: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testosterone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. Results: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). Conclusion: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.

Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result.

INTRODUCTION: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a posi¬tive second biopsy in males considered for re-biopsy. MATERIAL AND METHODS: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testos¬terone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. RESULTS: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). CONCLUSION: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?

BACKGROUND: Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP). METHODS: From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. RESULTS: Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 µM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non-cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). CONCLUSION: Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.

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.

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.

Detection rate of anterior prostate cancer in 226 patients submitted to initial and repeat transperineal biopsy.

OBJECTIVE: To evaluate the detection rate of anterior zone (AZ) prostate cancer (PCa) in patients submitted to initial and repeat transperineal prostate biopsy. METHODS: From January 2013 to August 2013, 226 patients (median age 64 years) with negative digital rectal examination underwent initial (144 cases) and repeat (82 cases) transperineal prostate biopsy for PSA >10 ng/ml, PSA 4.1-10.0 or 2.6-4.0 ng/ml with free/total PSA ≤25% and ≤20%, respectively. A median of 22 versus 32 cores were performed, including 4 cores of the AZ versus 6 cores (4 anterior plus 2 cores of the transition zone, TZ) at initial versus repeat biopsy, respectively. The detection rate of PCa of the peripheral zone (PZ), AZ and TZ was prospectively evaluated. RESULTS: The median PSA was 7.6 ng/ml; overall, a stage cT1c PCa was found in 104/226 (46%) patients, in 70 (48.6%) and 34 (41.5%) of the men who underwent initial and repeat biopsy, respectively. An AZ PCa was found in 11.5 vs. 8.8% (p = 0.32) of the patients submitted to initial versus repeat biopsy, respectively. AZ cancers demonstrated a number of positive cores (p = 0.03), greatest percentage of cancer (p = 0.001) and total percentage of cancer (p = 0.001) significantly lower in comparison with PZ PCa; moreover, 56.2 vs. 36.5% of AZ versus PZ PCa were characterized by a microfocus of cancer (p = 0.001), respectively. CONCLUSIONS: AZ biopsies increase the detection rate of PCa (about 10% of cases) at initial and repeat biopsy, allowing reduction of the biopsy false-negative rate.

Limited significance of activated Akt-mammalian target of rapamycin signaling pathway in prostate cancer progression.

OBJECTIVE: The objective of this study was to investigate the significance of the activated Akt-mammalian target of rapamycin (Akt-mTOR) signaling pathway in the progression of prostate cancer. MATERIALS AND METHODS: The expression levels of Akt, phosphorylated Akt (p-Akt), mTOR and phosphorylated mTOR (p-mTOR) in 175 prostate specimens, including 61 normal prostate tissues as a control, 24 high-grade prostatic intraepithelial neoplasias (HGPINs) and 90 clinically localized prostate cancers, were evaluated by immunohistochemical staining. p-Akt and p-mTOR ratios, which were defined as the expression level of p-Akt in relation to that of Akt and the expression level of p-mTOR in relation to that of mTOR, respectively, in these specimens were calculated. RESULTS: Expression levels of all four molecules, including Akt, p-Akt, mTOR and p-mTOR, were significantly greater in the HGPIN group compared with the normal control and prostate cancer groups. Furthermore, the p-Akt ratio in the prostate cancer group was significantly lower than that in the HGPIN group, while there was no significant difference in the p-mTOR ratio between the HGPIN and prostate cancer groups. In the prostate cancer group, no significant relationships were observed between major clinicopathological parameters and the expression levels as well as the ratios of p-Akt or p-mTOR. CONCLUSIONS: The Akt-mTOR signaling pathway may play a limited role in the progression of prostate cancer.

Prostate biopsy: results and advantages of the transperineal approach--twenty-year experience of a single center.

PURPOSE: Detection rate for prostate cancer (PCa) and complications following transperineal prostate biopsy (TPBx) were reported. METHODS: From January 1991 to December 2012, 4,000 men underwent TPBx; from 1991 to 2001, the patients underwent biopsy for suspicious DRE or PSA values >4 ng/mL; moreover, from 2002, the indications were abnormal DRE, PSA >10 ng/mL, PSA values between 4.1 and 10, 2.6 and 4 and <2.5 ng/mL with F/T PSA <25, <20 <15 %, respectively. In case of initial biopsy, the number of needles cores increased from 6 (1991-1996) to 12 (1997-2012) and 18 cores (2002-2012); in case of repeat biopsy, since 2005 a saturation biopsy (SPBx) with >24 cores was performed. RESULTS: Overall, PCa, normal parenchyma, HGPIN and ASAP were found in 1,379 (34.5 %), 2,400 (60 %), 175 (4.4 %) and 46 (1.1 %) patients, respectively; in case of initial TPBx, the scheme at 18 showed a greater PCa detection in comparison with scheme at 6-12 cores (p < 0.05). In case of repeat biopsy, a higher detection of microfocus of cancer was found performing a SPBx; moreover, 15 % of cancers were localized in the anterior zone. Incidence of hemospermia and urinary retention were correlated with the number of needle cores resulting equal to 30.4 versus 11.1 % in case of SPBx (p < 0.05); moreover, none developed sepsis. CONCLUSIONS: Transperineal prostate biopsy (TPBx) resets the risk of sepsis; moreover, in case of repeat SPBx, the transperineal approach detects a high number of significant PCa localized in the anterior zone (15 % of the cases).

Concomitant high-grade prostatic intraepithelial neoplasia is associated with good prognosis factors and oncologic outcome after radical prostatectomy.

OBJECTIVES: To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP). MATERIAL AND METHODS: We prospectively collected a single-institution database of 2,351 patients who underwent RP between 1998 and 2011. RESULTS: 1,272 (54.1%) patients had HGPIN on specimens. The mean follow-up was 28 months. Presence of HGPIN was significantly associated with a favorable preoperative risk status and with pathological factors of poor prognosis in RP specimens. Patients without HGPIN had a worse biochemical recurrence-free survival compared with those with HGPIN in RP specimen (log-rank test: p = 0.015). The 3-year RFS rate was 73.9% for the HGPIN group versus 67.2%. The absence of HGPIN was also significantly correlated with the use of androgen deprivation treatment during the follow-up (p < 0.001). In Cox multivariate analysis, taking into account the other prognostic pathological factors, HGPIN was not an independent predictive factor for PSA failure (p = 0.868). CONCLUSION: HGPIN is associated with factors of good prognosis but fails to show independent significance when classical pathological prognostic factors are taken into account.

Impact of PSA and DRE on histologic findings at prostate biopsy in Turkish men over 75 years of age.

Prostate specidic antigen (PSA) and digital rectal examination (DRE) are the known predictive factors for positive prostate biopsies differing according to the age, region and race. There have been only very limited studies about the impact of PSA on histological findings at prostate biopsy in Turkey. The aim of this study was to evaluate the impact of PSA and clinical stage on histologic findings of prostate biopsy in men older than 75 years of age as a first study in the Turkish population. A total of 1,645 consecutive prostate biopsies were included, with 194 men aged 75 or older. Cancer was identified in 104 patients (53.6%). Of the 104 positive biopsies, Gleason scores were less than 7 in 53 (49%) patients, 7 or greater in 51 (51%) patients. Positive prostate biopsies were significantly correlated with advanced age (p=0.0001), abnormal DRE (p=0.0001) and raised PSA (p=0.0001). The prostate volume was significantly correlated with advanced age especially in prostate cancer patients over 75 years, compared with those under 75 (p=0.0001). These results are useful for counseling men older than 75 years for prostate cancer detection. However, PCa screening decisions are currently based on urologist judgment and detection of latent asymptomatic disease is an important concern regarding costs, overdiagnosis, overtreatment and quality of life (QOL) for men aged 75 years and older. Healthy old patients with a long life expectancy need to be carefully evaluated for eligibility for PCa screening.

Sixth joint meeting of J-CaP and CaPSURE--a multinational perspective on prostate cancer management and patient outcomes.

This report summarizes the presentations and discussions that took place at the Sixth Joint Meeting of J-CaP and CaPSURE held in San Francisco, USA, in August 2012. The J-CaP and CaPSURE Joint Initiative was established in 2007 with the objective of analyzing, reviewing, comparing and contrasting data for prostate cancer patients from Japan and the USA within the two important large-scale, longitudinal, observational databases-J-CaP and CaPSURE. Since this initial collaboration between teams in the USA and Japan, the initiative has now expanded to include representatives of other Asian countries, several of whom have either established or are planning their own national prostate cancer databases. Several key topics were considered at this Sixth Joint Meeting including the current status of the J-CaP and CaPSURE databases and opportunities for collaboration with the more recently developed Asian prostate cancer databases. The latest comparative data from J-CaP and CaPSURE regarding outcomes following androgen deprivation therapy and combined androgen blockade were also reviewed. The possibility of a global chemoprevention trial to investigate the influence of soy isoflavones on prostate cancer incidence was considered. In addition, the ongoing debate regarding the role of screening and the use of active surveillance as a treatment option in the USA was discussed. The collaborators agreed that sharing of data and treatment practices on a global scale would undoubtedly benefit the clinical management of prostate cancer patients worldwide.

[Pilot study on predictive value of plasmatic levels of 9 angiogenetic biomarkers in selection of patients candidate to prostate biopsy]. / Studio pilota sul valore predittivo dei livelli plasmatici di 9 fattori angiogenetici nella selezione di pazienti candidati alla biopsia prostatica.

To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potential cut-off level was computed. Fifty patients were entered. Median PSA was 6.8 ng/mL. A prostate nodule was palpable in 18 (36%) patients. The median number of biopsy cores was 12. Prostate cancer was detected in 25 (50%) and ASAP and PIN in 2 more patients (4%) respectively. Among the 9 considered biomarkers, only leptin showed an interesting diagnostic performance with an AUC of 0.781, at a cut-off value of 2.11 ng/mL, demonstrating a sensitivity of 78%, a specificity of 77% and a positive predictive value of 85%. Main limitations of our study are the exploratory design and the criteria adopted for patients' selection determining a detection rate for prostate cancer above the usual range. Leptin only, in our preliminary study, shows promising diagnostic accuracy for the selection of patients candidate to prostate biopsy. Further studies are required to confirm its diagnostic value and its relation with BMI.

Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy patients.

BACKGROUND: The PCA3 urinary assay has shown promise in predicting the presence of prostate cancer. We evaluated the value of this test in patients undergoing initial and repeat prostate biopsy. METHODS: PCA3 and PSA levels were obtained from 456 men with no known personal history of prostate cancer prior to prostate biopsy. Two hundred eighty-nine men underwent an initial prostate biopsy and 167 underwent a repeat prostate biopsy. PCA3 and PSA levels were compared to the prostate biopsy results. RESULTS: PCA3 score was shown to be independent of prostate volume (P = 0.162) and PSA level (P = 0.959). PCA3 scores were significantly higher in patients with cancer on prostate biopsy compared to patients with negative biopsy results (P < 0.0001). In logistic regression, PCA3 showed a significantly higher AUC than PSA (0.726 vs. 0.512, P = 0.0001). This difference persisted when examining the initial biopsy subgroup, with PCA3 out-performing PSA (AUC 0.772 vs. AUC = 0.552, P < 0.0001), but not in the repeat biopsy subgroup (AUC = 0.605 vs. AUC = 0.500, P = 0.2488). CONCLUSIONS: PCA3 was found to be a better predictor of prostate cancer than PSA in the total population as well as the initial biopsy population, but was not superior to PSA in the repeat biopsy population. Prostate 73: 48-53, 2013. © 2012 Wiley Periodicals, Inc.