Men Undergoing Prostate Needle Biopsy Research Articles

Circulating microRNAs in plasma as potential biomarkers for the early detection of prostate cancer.

MicroRNAs (miRNAs) have been linked to prostate cancer (PC) risk; however, their role as a screening biomarker for PC has yet to be determined. We examined whether circulating miRNAs in plasma could be potential biomarkers for the early detection of PC among men undergoing prostate needle biopsy. Men who had a prostate biopsy due to an abnormal screening test were recruited. Linear regression was used to examine the association between miRNAs in plasma and PC status and to model individual miRNA expression on serum PSA and age to calculate the partial correlation coefficient (r). There were 134 men, aged 46-86 years, included, with 66 men with a PC diagnosis (cases), eight men with no PC diagnosis but atypical lesion, and 60 men without a PC diagnosis (controls). The most statistically significant PC circulating miRNAs were miR-381, miR-34a, miR-523, miR-365, miR-122, miR-375, miR-1255b, miR-34b, miR-450b-5p, and miR-639 after adjusting for age (P-values ≤0.05); however, they were no longer statistically significant after P-value adjustment for multiple comparisons. MiR-671-3p was differentially expressed between black and white cases (P-value = 0.03). Moderate positive correlations with serum PSA were observed for miR-381 overall and among controls (r = 0.43-0.60; P-values ≤0.05) and miR-34a among cases (r = 0.46; P-value = 0.02). There was no miRNA associated with PC diagnosis after adjusting for age and P-values; however, moderate correlations between miRNAs and serum PSA were observed. Further investigation between miRNAs and PC risk is warranted in a larger population at high risk for PC.

Preoperative urine culture is unnecessary in asymptomatic men prior to prostate needle biopsy.

To determine the clinical utility of preoperative urine cultures in asymptomatic men undergoing prostate needle biopsy (PNB). One hundred fifty asymptomatic men had urine cultures obtained 14-days prior to PNB. As per study protocol, positive cultures were not treated. Antibiotic prophylaxis prior to PNB included ciprofloxacin 500mg the night before and morning of the biopsy. Repeat urine cultures were obtained immediately prior to PNB with colony-forming units (CFUs) annotated. Infectious complications post-biopsy were recorded. Of the 150 men, six patients (4%) had evidence of asymptomatic bacteriuria with>10,000CFU/mL on office urine culture. Repeat urine cultures on morning of biopsy in all 150 patients noted a mean bacterial count of 55CFU/mL (range 0-1000). All six patients with positive office urine cultures had<100CFU/mL at time of PNB. Following biopsy, four patients (2.7%) developed an infectious complication including two with sepsis and two with culture-positive UTIs. The causative organism in all cases was quinolone-resistant E. coli. None of the six patients with preoperative positive urine cultures developed an infectious complication following PNB. In this prospective observational study, under 5% of asymptomatic men had positive office cultures prior to PNB. Furthermore, repeat urine culture on the morning of biopsy showed resolution in these patients, and none developed post-biopsy infectious complications. Routine office urine culture in the asymptomatic male prior to PNB was unnecessary.

Abstract 4241: Circulating microRNAs in plasma of men screened for prostate cancer

Abstract Introduction: Although microRNAs (miRNAs) have been linked to prostate cancer risk, their role as a screening biomarker for prostate cancer (PC) has yet to be determined. We examined whether circulating miRNAs in plasma could be potential biomarkers for the early detection of PC among men undergoing prostate needle biopsy. Methods: Men who had a prostate biopsy due to an abnormal screening test were recruited. Demographics, medical history, clinical information, and blood processed into plasma were collected. TaqMan Low Density Arrays were used for the expression profiling of 733 miRNAs in plasma. Wilcoxon test was used to compare expression levels between men with and without a PC diagnosis. Logistic regression was used to examine the association between miRNAs and PC status, after adjusting for age and Bonferroni-correction. Results: There were 131 men, aged 46 to 86 years, included in the final analysis, with 66 men diagnosed with PC on prostate biopsy and 65 men without a PC diagnosis. Majority were white (72.5%) followed by black race (13.5%). Men with PC were older (median: 64 vs. 62 years; p-value = 0.16) and had statistically significantly higher serum PSA (median: 5.8 vs. 5.1 ng/mL; p-value = 0.01) compared to men without a PC diagnosis. The most statistically significant PC circulating miRNAs in plasma were miR-381, miR-523, miR-450B-5p, miR-34a, miR-34b, miR-639, and miR-365, after adjusting for age (p-values ≤ 0.05). The detection rate of these miRNAs in plasma ranged from 23.7% to 83.2%. These miRNAs were no longer statistically significant with PC diagnosis, after adjusting for multiple comparison (FDR q-value = 1.00). Conclusion: Among the 733 miRNAs evaluated, there was no miRNA found to be associated with PC diagnosis after adjusting for multiple comparison. Studies that examine a larger number of miRNAs which include the discovery of new miRNAs and their relationship with PC risk are warranted. Citation Format: Alicia C. Mcdonald, Jing Shen, Manish Vira, Martin Sanda, Jason Liao, Martin L. Lesser, Dattatraya Patil, Jay D. Raman, Emanuela Taioli. Circulating microRNAs in plasma of men screened for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4241. doi:10.1158/1538-7445.AM2017-4241

Neutrophil-to-lymphocyte ratio predicts prostatic carcinoma in men undergoing needle biopsy

Neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammatory response, has been demonstrated as an independent prognosticator for some solid malignancies, including prostate cancer. In the present study, we evaluated the role of NLR in men who underwent prostate needle biopsy for their initial diagnosis of prostatic carcinoma. Both complete blood counts and free/total (F/T) prostate-specific antigen (PSA) ratio were examined in a total of 3,011 men in our institution. Of these, 1,207 had a PSA level between 4 and 10 ng/mL, and 357 of 810 who subsequently underwent prostate needle biopsy were found to have prostatic adenocarcinoma. NLR value was significantly higher in men with PSA of ≥ 20 ng/mL than in those with PSA of < 20 ng/mL (p < 0.001). NLR was also significantly higher in men with positive biopsy than in those with negative biopsy (p < 0.001). Using NLR cut-off point of 2.40 determined by the AUROC curve, positive/negative predictive values of NLR alone and NLR combined with F/T PSA ratio (cut-off: 0.15) were 56.6%/60.8% and 80.7%/60.1%, respectively. Multivariate analysis revealed that not only F/T PSA ratio (HR = 3.13) but also NLR (HR = 2.21) was an independent risk factor for prostate cancer. NLR is thus likely elevated in patients with prostate cancer. Accordingly, NLR, with or without combination with F/T PSA ratio, may function as a new biomarker to predict prostate cancer in men undergoing prostate needle biopsy.

Metformin effects on biochemical recurrence and metabolic signaling in the prostate.

Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. One thousand seven hundred and thirty four men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa. Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use.

MP55-15 INVOLVEMENT OF MIR-181B-MEDIATED EZH2/IGF-1R SIGNALLING PATHWAY IN THE GROWTH AND ENERGY METABOLISM OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Metformin has received considerable attention as a potential anti-cancer agent. Animal and invitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. This may include increased AMPK activity or a reduction of hyperinsulinemia and insulin signaling. We studied the effect of pharmacologic metformin dosages on prostate gland expression of AMPK, insulin and IGF-1 receptor activity. METHODS: Subjects were identified from a clinical and tissue database from the Seattle-Puget Sound Veteran’s Affairs Medical Center. Cases included men who were continuously taking metformin ( 500mg daily) for at least 6 months prior to the biopsy compared to controls not taking metformin. Controls were matched 1:1 to cases on age, race, BMI and whether PCa was detected. AMPK, insulin receptor (IR), insulin-like growth factor 1 receptor (IGF-IR) and AKT protein expression was assessed by immunohistochemistry. Differences in the mean IHC scores between the two groups were compared with linear regression adjusted for age, race, BMI and fasting glucose based on (1) presence or absence of prostate cancer and (2) metformin exposure. RESULTS: We identified 48 patients taking metformin and 41 controls who underwent prostate biopsy. Of these, 46% had cancer detected. The majority of men were Caucasian (82%), obese (59%) and over the age of 65 (58%). In patients with PCa detected at biopsy, significant increases in IGF-1R (p1⁄40.002), IR (p<0.001), AKT (p<0.001) and AMPK (p<0.001) were found compared to men with negative prostate biopsies. Among metformin users, IGF-1R remained significantly elevated (p1⁄40.01) in men with cancer detected whereas pAMPK expression (p1⁄40.05) was greater only in those without prostate cancer. CONCLUSIONS: In men undergoing prostate needle biopsy, AMPK, IR, and IGF-1R are increased in those with PCa detected compared to those with negative biopsies. When stratified by metformin, AMPK was elevated in negative biopsies while IGF-1R remained elevated in those with cancer. This suggests a mechanistic affect of metformin use on decreased insulin signaling/reception while maintaining elevated AMPK signaling. This may provide a therapeutic benefit in prostate cancer development by decreasing downstream activation of mammalian target of rapamycin (mTOR) signaling and subsequent proliferation. Further longitudinal study is needed to assess dose response and confirm this relationship.

MP55-14 METFORMIN USE AND METABOLIC SIGNALING IN MEN UNDERGOING PROSTATE NEEDLE BIOPSY

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2015MP55-14 METFORMIN USE AND METABOLIC SIGNALING IN MEN UNDERGOING PROSTATE NEEDLE BIOPSY Brian Winters, Sarah Holt, Xiaotun Zhang, Colm Morrissey, Daniel Lin, Stephen Plymate, and Jonathan Wright Brian WintersBrian Winters More articles by this author , Sarah HoltSarah Holt More articles by this author , Xiaotun ZhangXiaotun Zhang More articles by this author , Colm MorrisseyColm Morrissey More articles by this author , Daniel LinDaniel Lin More articles by this author , Stephen PlymateStephen Plymate More articles by this author , and Jonathan WrightJonathan Wright More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2057AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. This may include increased AMPK activity or a reduction of hyperinsulinemia and insulin signaling. We studied the effect of pharmacologic metformin dosages on prostate gland expression of AMPK, insulin and IGF-1 receptor activity. METHODS Subjects were identified from a clinical and tissue database from the Seattle-Puget Sound Veteran's Affairs Medical Center. Cases included men who were continuously taking metformin (≥ 500mg daily) for at least 6 months prior to the biopsy compared to controls not taking metformin. Controls were matched 1:1 to cases on age, race, BMI and whether PCa was detected. AMPK, insulin receptor (IR), insulin-like growth factor 1 receptor (IGF-IR) and AKT protein expression was assessed by immunohistochemistry. Differences in the mean IHC scores between the two groups were compared with linear regression adjusted for age, race, BMI and fasting glucose based on (1) presence or absence of prostate cancer and (2) metformin exposure. RESULTS We identified 48 patients taking metformin and 41 controls who underwent prostate biopsy. Of these, 46% had cancer detected. The majority of men were Caucasian (82%), obese (59%) and over the age of 65 (58%). In patients with PCa detected at biopsy, significant increases in IGF-1R (p=0.002), IR (p<0.001), AKT (p<0.001) and AMPK (p<0.001) were found compared to men with negative prostate biopsies. Among metformin users, IGF-1R remained significantly elevated (p=0.01) in men with cancer detected whereas p-AMPK expression (p=0.05) was greater only in those without prostate cancer. CONCLUSIONS In men undergoing prostate needle biopsy, AMPK, IR, and IGF-1R are increased in those with PCa detected compared to those with negative biopsies. When stratified by metformin, AMPK was elevated in negative biopsies while IGF-1R remained elevated in those with cancer. This suggests a mechanistic affect of metformin use on decreased insulin signaling/reception while maintaining elevated AMPK signaling. This may provide a therapeutic benefit in prostate cancer development by decreasing downstream activation of mammalian target of rapamycin (mTOR) signaling and subsequent proliferation. Further longitudinal study is needed to assess dose response and confirm this relationship. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e678 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian Winters More articles by this author Sarah Holt More articles by this author Xiaotun Zhang More articles by this author Colm Morrissey More articles by this author Daniel Lin More articles by this author Stephen Plymate More articles by this author Jonathan Wright More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prostate cancer diagnosis is associated with an increased risk of erectile dysfunction after prostate biopsy

To evaluate prospectively the characteristics, erectile function and lower urinary tract symptoms (LUTS) of men undergoing prostate needle biopsy (PNBx). From 2008 to 2011, 134 men were prospectively administered the International Index of Erectile Function (IIEF), American Urological Association Symptom Index (AUA-SI), and quality-of-life (QoL) questionnaires before and after undergoing a single 12-core PNBx. Comparisons of IIEF and AUA-SI scores before and after PNBx, based upon baseline characteristics and prostate cancer (PCa) diagnosis, were performed. Univariable and multivariable logistic regression models were used to characterize predictors of change in IIEF scores. In the 85 men who fulfilled the inclusion criteria, there were no significant differences between the mean (sd) total pre-biopsy and the mean (sd) post-biopsy IIEF scores: 57.8 (12.9) vs 54.3 (17.2). Subgroup analysis showed that men who had biopsy-proven PCa had significantly greater changes in their post-biopsy IIEF scores compared with men without (-10.1 vs. 1.0; P < 0.001). After specific analyses of the IIEF domains in these groups we found significant decreases in every domain, including erectile function (P = 0.01). On multivariate analyses, only PCa diagnosis was associated with a significant change in IIEF (odds ratio 7.2; P = 0.003). There were no differences in AUA-SI or QoL scores in the overall population or in subgroups. Cancer diagnosis appears to have an adverse effect on the erectile function of men undergoing PNBx but no effect on LUTS. This study highlights a potential negative psychological confounder that may influence erectile function before the treatment of PCa. Additional prospective trials evaluating these relationships are warranted.

Is high-grade prostatic intraepithelial neoplasia on needle biopsy different in an Asian population: A clinicopathologic study performed in Singapore

Objectives To evaluate the incidence, pathologic findings, and follow-up of high-grade prostatic intraepithelial neoplasia (HGPIN) in a series of prostate core biopsies from Singaporean men. Methods We studied isolated HGPIN diagnosed on prostate core biopsies and the incidence of cancer discovered in men who had undergone repeat biopsies from 1999 to 2003 at the Department of Pathology, Singapore General Hospital. Results Of 1219 men undergoing prostate needle biopsy, 56 (4.6%) had isolated HGPIN. Most cases affected a single prostate core (44 cases, 78.6%). Twenty-nine men (51.8%) underwent repeat biopsies. Cancer was discovered in 7 (24.1%) of the 29 men within two repeat biopsies. Conclusions The incidence of isolated HGPIN on prostate needle core biopsies in Asian men, as well as the likelihood of subsequent cancer detection, are comparable to the rates reported for Western populations. The relatively low yield of cancer detection on repeat biopsy supports the need to re-evaluate recommendations for rebiopsy strategies.

Are men with larger prostates and bothersome voiding symptoms less likely to have significant prostate cancer?

4656 Background: Gleason Sum (GS) predicts clinically significant prostate cancer (CAP) and prostate specific antigen (PSA) survival in men undergoing prostatectomy for CAP. BPH can also elevate PSA. Objective: evaluate prostate gland volume (PV) and American Urologic Symptom Score (AUASS) in men undergoing prostate needle biopsy (PNB) to detect CAP. Analysis endpoints: 1) CAP and 2) GS ≥7. Methods: From 1/2000–7/2005, 1,078 men undergoing PNB were prospectively examined. Urinary voiding symptoms were measured by AUASS. All men were examined by 1 surgeon: DRE and Transrectal Ultrasound (TRUS) were given levels of suspicion (LOS) from 1 = low suspicion (smooth DRE, homogeneous TRUS) to 5 = high suspicion (hard DRE, hypoechoic lesion). LOS ≥3 was abnormal. Prebiopsy parameters: PSA, DRE, age, race, biopsy history, prostate volume (PV), TRUS lesion, and AUASS. All men had 10-core biopsy. 1) Predictors for CAP were evaluated by Univariate (UVA) and multivariate (MVA) analysis (logistic regression) for 1,078 men. 2) Predictors for GS≥7 were evaluated in men with no prior biopsy (NOPB). Results: Median PSA = 5.4 ng/ml (mean 10.4), 38% and 52% had abnormal TRUS &amp; DRE respectively. Mean patient age = 64 years. Mean AUASS = 10.4. Positive biopsy rate = 38%. AUASS: 47% had low symptoms scores (&lt;7), 39% had moderate scores (8–19), and 14% had severe scores (20–35). UVA &amp; MVA (N = 1,078) showed that PSA was not an independent predictor of CAP (p = 0.18), but abnormal DRE, age, low AUASS, no prior biopsy (NOPB), race (AA), abnormal TRUS, and low PV were all independent predictors (p &lt; 0.03). Subset MVA analysis of men in PSA range of 2.5–10 (N = 738), demonstrated that low AUASS (p = 0.05) &amp; low PV (p = 0.00001) were predictors of CAP, while DRE, NOPB, and age were also independent predictors. MVA of men with NOPB (N = 790), indicated that low PV, PSA, DRE, and Age were independent predictors for CAP (p &lt; 0.0001). The multivariate risk of having GS ≥7 on biopsy was independently associate with both low PV (p = 0.001) and abnormal DRE (p = 0.001). The relationship between PV and GS ≥7 showed that for every 1 cc increase in gland volume the risk of GS ≥7 CAP decreases by 2.2%. Conclusions: Men with smaller prostates are more likely to have cancer and are more likely to have significant disease. No significant financial relationships to disclose.

Prostate Specific Antigen Remains an Independent Predictor of Cancer at Prostate Biopsy in Black American Men But Not in White Men: Results from a Consecutive Series of 914 Men

Black American men may be at increased risk for prostate cancer but differences in prebiopsy parameters between black and white men have not been fully examined. Therefore, we identified the prebiopsy parameters that may be predictive of prostate cancer in black and white men. From January 2000 to July 2004, 914 consecutive men undergoing prostate needle biopsy were prospectively examined by a single urologist. Urinary symptoms were measured by AUASS. Prebiopsy parameters recorded were PSA, free PSA, DRE, age, race, biopsy history, prostate volume, TRUS lesion and AUASS. Prostate biopsy was performed in 914 men with a mean age of 63.9 years. Mean PSA in the entire cohort was 11.2 ng/ml (median 5.8). Abnormal TRUS and abnormal DRE were found in 37% and 52% of men, respectively. Mean AUASS was 9.6. The overall positive biopsy rate was 37%. In black and white men the positive biopsy rate was 44% and 34%, respectively. Analysis of AUASS indicated that 47% of patients had low symptom scores (less than 7), 39% had moderate scores (8 to 19) and 14% had severe scores (20 to 35). Multivariate analysis revealed that PSA was an independent predictor of positive biopsy in black but not in white men (p = 0.001 and 0.79, respectively). Multivariate analysis also showed that race alone was an independent predictor of positive prostate biopsy (p = 0.013). PSA remains an independent predictor of positive prostate biopsy on multivariate analysis. Other independent predictors are black race, age, low AUASS, prostate volume, abnormal DRE, no previous biopsy and abnormal TRUS. In the black group low AUASS, PSA, no previous biopsy and DRE were unique independent predictors, while in the white group age and abnormal TRUS were unique predictors.

PREDICTORS OF UTILITIES FOR HEALTH STATES IN EARLY STAGE PROSTATE CANCER

When faced with treatment choices for early stage prostate cancer, patients must balance the survival benefit of a treatment with its morbidity. Little is known about how patients balance these trade-offs. To further our understanding of patient decision making we assessed patient utilities for prostate cancer treatment related morbidities. We determined whether patient utilities were predicted by sociodemographic characteristics or baseline genitourinary function. We evaluated 401 men undergoing prostate needle biopsy for suspicion of prostate cancer at university, Veterans Affairs and public hospitals. Study design included a prospective cross-sectional cohort with correlation and multivariate analysis. Subjects were studied with 2 established health related quality of life instruments. Patient utilities were assessed with an interactive software application. On multivariate analysis utility for current general health was a significant predictor of utilities for treatment related morbidities. Surprisingly baseline urinary, sexual and bowel function scores did not correlate well with respective utilities for potential incontinence, impotence or radiation proctitis. In other words, men with good and imperfect baseline function were equally willing to risk impairment to preserve life. Men who perceived that general health was better appear to place higher value on quantity of life, while those who already are suffering from poor general health place higher value on quality of life. Ethnicity appears to modify some effects of other variables on patient preference. Utility assessment provides a quantitative tool to aid physicians in counseling patients when making treatment decisions for localized prostate cancer.