Background: To examine whether diagnostic biopsy (B1), for patients on active surveillance (AS) for prostate cancer, performed at an outside referral centre (external) compared with our in-house tertiary center (internal), increased the risk of re-classification on the second (confirmatory) biopsy (B2). Methods: Patients on AS were identified from our tertiary center database (1997–2012) with PSA<10, Gleason sum (GS) ⩽6, clinical stage ⩽cT2, ⩽3 positive cores, <50% of single core involved, age ⩽75 years and having a B2. Patients who had <10 cores at B1 and delay in B2 >24 mo were excluded. Depending on center where B1 was performed, men were dichotomized to internal or external groups. All B2 were performed internally. Multivariate logistic regression examined if external B1 was a predictor of re-classification at B2. Results: A total of 375 patients were divided into external ( n =71, 18.9%) and internal groups ( n =304, 81.1%). At B2, more men in the external group re-classified (26.8%) compared with the internal group (13.8%)( P =0.008). On multivariate analysis, external B1 predicted grade-related re-classification (odds ratio (OR) 4.14, confidence interval (CI) 2.01–8.54, P <0.001) and volume-related re-classification (OR 3.43, CI 1.87–6.25, P <0.001). Other significant predictors for grade-related re-classification were age (OR 2.13 per decade, CI 1.32–3.57, P <0.001), PSA density (OR 2.56 per unit, CI 1.44–4.73, P <0.001), maximum % core involvement (OR 1.04 per percentage point, CI 1.01–1.09, P =0.02) and time between B1 and B2 (OR 1.43 per 6 months, CI 1.21–1.71, P <0.001). Conclusion: At our institution, patients on AS who had their initial B1 performed externally were more likely to have adverse pathological features and re-classify on internal B2.

Background: Many men (21-52%) are reported to have no cancer on the second, also known as the confirmatory, biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased.Objective: To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression.Design, setting, and participants: Men were identified from our tertiary care center AS prostate cancer database (1995-2012). Eligibility criteria were prostate-specific antigen (PSA) <= 10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2.Intervention: AS.Outcome measurements and statistical analysis: Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model.Results and limitations: Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5-61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively (p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29-0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20-0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12-2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00-1.10; p = 0.04). Retrospective analysis was the major limitation of the study.Conclusions: Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 20111780 5-ALPHA REDUCTASE INHIBITORS DIMINISH THE RATE OF PROGRESSION IN MEN WITH LOW RISK PROSTATE CANCER ON ACTIVE SURVEILLANCE Antonio Finelli, Greg Trottier, Nathan Lawrentschuk, Robert J. Sowerby, Alexandre R. Zlotta, Lenny Radomski, Narhari Timilshina, Andrew Evans, Theodorus H. van der Kwast, Ants Toi, Micheal A.S. Jewett, John Trachtenberg, and Neil E. Fleshner Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Nathan LawrentschukNathan Lawrentschuk Toronto, Canada More articles by this author , Robert J. SowerbyRobert J. Sowerby Toronto, Canada More articles by this author , Alexandre R. ZlottaAlexandre R. Zlotta Toronto, Canada More articles by this author , Lenny RadomskiLenny Radomski Toronto, Canada More articles by this author , Narhari TimilshinaNarhari Timilshina Toronto, Canada More articles by this author , Andrew EvansAndrew Evans Toronto, Canada More articles by this author , Theodorus H. van der KwastTheodorus H. van der Kwast Toronto, Canada More articles by this author , Ants ToiAnts Toi Toronto, Canada More articles by this author , Micheal A.S. JewettMicheal A.S. Jewett Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , and Neil E. FleshnerNeil E. Fleshner Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2130AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 5-alpha reductase inhibitors (5ARIs) have been shown to prevent prostate cancer in two large randomized controlled trials. No prior work has shown the effect of 5ARIs on those already diagnosed with low risk prostate cancer. Our goal was to determine the effect of 5ARIs on pathologic progression in men on active surveillance for prostate cancer. METHODS This was a single institution retrospective cohort study comparing men taking a 5ARI versus no 5ARI while on active surveillance for prostate cancer. All men had at least two biopsies. Inclusion criteria for active surveillance were PSA <10 ng/ml, clinical stage T1c/T2a, Gleason score <6, and <3 cores positive with no more than 50% of a core involved at initial diagnostic biopsy. Pathologic progression was evaluated and defined as Gleason score >6, or maximum core involvement >50% or >3 cores positive on a follow-up prostate biopsy. Univariate, multivariate and Kaplan-Meir analyses were conducted. RESULTS A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 months (IQR 23.6–59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%, p=0.004) and were less likely to abandon active surveillance (20% vs 37.6%, p=0.006). The median time to progression was longer in the 5ARI group (42.5 months) compared to the non-5ARI group (31.5 months; p=0.026). On multivariate analysis, lack of 5ARI use was most strongly associated with pathologic progression (OR 2.98, 95% CI 1.5–5.9) followed by age and baseline maximum percentage involvement of any biopsy core. CONCLUSIONS 5ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e715 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Antonio Finelli Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Nathan Lawrentschuk Toronto, Canada More articles by this author Robert J. Sowerby Toronto, Canada More articles by this author Alexandre R. Zlotta Toronto, Canada More articles by this author Lenny Radomski Toronto, Canada More articles by this author Narhari Timilshina Toronto, Canada More articles by this author Andrew Evans Toronto, Canada More articles by this author Theodorus H. van der Kwast Toronto, Canada More articles by this author Ants Toi Toronto, Canada More articles by this author Micheal A.S. Jewett Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Neil E. Fleshner Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PURPOSE:We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance.MATERIALS AND METHODS:Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression.RESULTS:A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02).CONCLUSIONS:Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk.

You have accessJournal of UrologyProstate Cancer: Localized (III)1 Apr 2013662 THE SIGNIFICANCE OF FINDING NO PROSTATE CANCER ON THE ACTIVE SURVEILLANCE CONFIRMATORY BIOPSY: IMPLICATIONS FOR PATHOLOGICAL RE-CLASSIFICATION Lih-Ming Wong, Greg Trottier, Nathan Lawrentschuk, Narhari Timilshina, Girish Kulkarni, Robert Hamilton, John Trachtenberg, Alexandre Zlotta, Ants Toi, Neil Fleshner, and Antonio Finelli Lih-Ming WongLih-Ming Wong Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Nathan LawrentschukNathan Lawrentschuk Toronto, Canada More articles by this author , Narhari TimilshinaNarhari Timilshina Toronto, Canada More articles by this author , Girish KulkarniGirish Kulkarni Toronto, Canada More articles by this author , Robert HamiltonRobert Hamilton Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , Alexandre ZlottaAlexandre Zlotta Toronto, Canada More articles by this author , Ants ToiAnts Toi Toronto, Canada More articles by this author , Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author , and Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.217AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A significant proportion of men are consistently reported to have no cancer on the 2nd, also known as the confirmatory, biopsy (B2) for active surveillance (AS). Intuitively, this group of men may have lower volume disease and could benefit from less intensive follow up. We investigate if men on AS with no cancer found at B2, are less likely to undergo subsequent pathological re-classification. METHODS Patients were identified from our tertiary care referral centre AS database (1997-2012). Eligibility criteria were PSA ≤10, clinical stage ≤T2, ≤ 3 positive cores involved, no core >50% involved and age ≤75. Patients who did not undergo a 3rd or subsequent biopsy, because of either ceasing AS after the 2nd biopsy or having insufficient follow up, were excluded. The patients on AS with ≥3 biopsies (n=286) were dichotomized on the basis of cancer status (yes or no) at B2. A Cox proportional hazards model was used to examine if absence of cancer at B2 was a predictor for re-classification. Pathological re-classification was defined as grade (GS ≥7) and/or volume (PCores >3, >50% single core involved). Re-classification free probability estimates were calculated by the Kaplan-Meier method and comparisons between curves made by the log rank test. RESULTS Of the 286 patients analysed at B2, 149 (52%) had no cancer and 137 (48%) had cancer satisfying eligibility criteria to remain on AS. The median follow-up for our cohort was 41 months, (IQR 26.5-61.9). The proportion of patients that re-classified on subsequent biopsies were 23.5% (no cancer group) and 40.1% (cancer group). The most common method of re-classification for the no cancer group was grade-only (48.6%), whereas for the cancer group, volume-only re-classification (41.8%) occurred the most frequently. The probability of remaining free of pathological re-classification at 2 and 5 years, stratified by cancer status on B2, for the no cancer group was 96.6% and 85.2% and the cancer group 92.7% and 67.3% respectively (log rank, p=0.002). No cancer at B2 was associated with a 54% reduction in risk of subsequent re-classification (HR 0.46, p=0.002). Increasing age (HR 1.06, p=0.001) and PSA density (HR 1.49, p=0.04) were predictors of re-classification. CONCLUSIONS Absence of cancer on the 2nd biopsy is associated with a significant decreased risk of pathological re-classification. When re-classification does occur, it tends to be grade-related. Hence, whilst frequency of re-biopsy could be reduced in this group, re-biopsy remains an essential component of follow-up in all patients on AS. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e270-e271 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Metrics Author Information Lih-Ming Wong Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Nathan Lawrentschuk Toronto, Canada More articles by this author Narhari Timilshina Toronto, Canada More articles by this author Girish Kulkarni Toronto, Canada More articles by this author Robert Hamilton Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Alexandre Zlotta Toronto, Canada More articles by this author Ants Toi Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Markers (II)1 Apr 20132241 VALIDATION OF SERUM ADIPOKINES FOR PREDICTION OF PROSTATE CANCER IN A PROSPECTIVE COHORT STUDY Bimal Bhindi, Girish Kulkarni, David Margel, Haiyan Jiang, Ghazi Al-Edwan, Karen Chadwick, Greg Trottier, and Neil Fleshner Bimal BhindiBimal Bhindi Toronto, Canada More articles by this author , Girish KulkarniGirish Kulkarni Toronto, Canada More articles by this author , David MargelDavid Margel Toronto, Canada More articles by this author , Haiyan JiangHaiyan Jiang Toronto, Canada More articles by this author , Ghazi Al-EdwanGhazi Al-Edwan Toronto, Canada More articles by this author , Karen ChadwickKaren Chadwick Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , and Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2150AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PC) and obesity are both considered diseases of Westernization. Cytokines secreted by adipocytes, called adipokines, may link the two. We previously demonstrated in a small case control pilot study that certain circulating adipokines can help in the prediction of PC among men presenting for a prostate biopsy. The aim of this study was to validate our findings in a larger novel cohort. METHODS We derived patients from our prostate biopsy database and analyzed prospectively collected BioBank specimens. Eligible patients for this study included those presenting for first biopsy who were not diabetic or on a statin. All adipokine assays were performed in a different laboratory than the original pilot cohort. Adipokines studied were resistin, tumor necrosis factor α (TNF-α), interleukin −6 (IL-6), nerve growth factor (NGF), hepatocyte growth factor (HGF) and monocyte chemoattractant protein?1 (MCP-1). Analyzed covariates were age, prostate specific antigen (PSA), and digital rectal exam (DRE) anomalies. As per our pilot study, obese and non-obese patients were analyzed separately. Following univariate statistics, multivariable predictive models were constructed and internally validated. Receiver operator characteristic (ROC) curve analyses were performed to determine associations and marginal benefits of adipokines for clinical PC prediction. RESULTS Of the final cohort of 1061 patients, median age, PSA, and BMI were 61.8 years, 5.3ng/ml, and 26.6kg/m2, respectively. 47.7% had PC at biopsy and 29.5% had high grade (HG) PC (Gleason ≥7). None of the adipokines were strongly correlated with PSA (each ürü<0.1). UNIVARIATE ANALYSES: Among non-obese patients, resistin and high HGF were associated with PC diagnosis, while IL-6 was associated with HG-PC. In obese patients, low MCP-1 was associated with PC diagnosis. ROC ANALYSES: For the model predicting PC diagnosis in non-obese patients, adding resistin, TNF-α and MCP-1 to the model (along with age, DRE and PSA) significantly improved the AUC from 0.70 to 0.74. For predicting HG-PC in non-obese patients, adding IL-6 and MCP-1 increased the AUC from 0.75 to 0.77. In obese patients, adding IL-6 and MCP-1 to the model predicting PC increased the AUC from 0.68 to 0.70. For predicting HG-PC in obese patients, adding HGF and NGF to the model improved the AUC from 0.74 to 0.75. CONCLUSIONS At the present date, there is no single biomarker that alone has strong predictive value for PC. Adipokines show promise in contributing additional predictive value to multivariable models consisting of classical risk factors. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e918-e919 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bimal Bhindi Toronto, Canada More articles by this author Girish Kulkarni Toronto, Canada More articles by this author David Margel Toronto, Canada More articles by this author Haiyan Jiang Toronto, Canada More articles by this author Ghazi Al-Edwan Toronto, Canada More articles by this author Karen Chadwick Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Localized (VII)1 Apr 20131498 ACTIVE SURVEILLANCE PROSTATE RE-BIOPSY SCHEMA: RESULTS OF ROUTINE TRANSITION ZONE BIOPSIES Lih-Ming Wong, Greg Trottier, Ants Toi, Alexandre Zlotta, Narhari Timilshina, Andrew Evans, Theo Van der Kwast, Michael Jewett, Girish Kulkarni, Robert Hamilton, John Trachtenberg, Neil Fleshner, and Antonio Finelli Lih-Ming WongLih-Ming Wong Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Ants ToiAnts Toi Toronto, Canada More articles by this author , Alexandre ZlottaAlexandre Zlotta Toronto, Canada More articles by this author , Narhari TimilshinaNarhari Timilshina Toronto, Canada More articles by this author , Andrew EvansAndrew Evans Toronto, Canada More articles by this author , Theo Van der KwastTheo Van der Kwast Toronto, Canada More articles by this author , Michael JewettMichael Jewett Toronto, Canada More articles by this author , Girish KulkarniGirish Kulkarni Toronto, Canada More articles by this author , Robert HamiltonRobert Hamilton Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author , and Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2977AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate re-biopsy schema for most published active surveillance (AS) cohorts is based on a standard extended template sampling the peripheral zone (PZ). In an AS population, we investigate the effect of routine transition zone (TZ) biopsy by examining the amount of TZ cancer found and its subsequent impact on pathological re-classification. METHODS Patients were identified from our tertiary referral centre AS database (1997-2012). Eligibility criteria included PSA <10, clinical stage ≤2, Gleason score (GS) ≤6, number of positive cores (PCore) ≤3, no single core >50% involved, age ≤75 years and at least 1 prostatic re-biopsy after diagnosis. Biopsies of the TZ were taken routinely after the diagnostic biopsy (B1). By mapping location of all PCores found, patients with cancer and pathological re-classification in the TZ could be identified at each AS biopsy. As the number of TZ cores taken is usually limited to 1-2, pathological re-classification for TZ cancers was defined as GS≥7 and/or >50% single core involved. Number of PCores was not used. Logistical regression was performed to identify features at diagnostic biopsy that could predict TZ-only reclassification on the 2nd, otherwise known as the confirmatory biopsy (B2). RESULTS The frequency of cancer, and reclassification, found in the TZ during subsequent biopsies during AS is shown in Table 1. At each re-biopsy, there was a consistent proportion of men that had TZ cancer detected (13.5-16.6%), and TZ re-classification (7.1-9.8%). After excluding men who re-classified in both TZ and PZ, the frequency of TZ-only re-classification at each biopsy was 4.8-8.4%. There was a total 64 TZ-only re-classification events in our cohort. Breakdown of re-classification type was: >50% single core involved (n=47), GS≥7 (n=12), both criteria (n=5). Of the 17 men with TZ grade-related re-classification, most were GS=3+4 (n=15), with few GS4+3 (n=1) and GS 4+4 (n=1). On univariate analysis, only % of core involved at B1 was predictive of TZ-only re-classification at B2 (OR1.04, 1.01-1.09, p=0.008). CONCLUSIONS Routine TZ biopsy during AS detects cancer in ∼15% of men at each biopsy. However, only 5% of men at each biopsy re-classify in only in the TZ, and most of these are with GS 3+4 disease. Our results suggest TZ biopsy could be performed less frequently or even not performed at all during routine AS re-biopsy. Frequency of TZ cancer and TZ re-classification found at each subsequent biopsy during AS Biopsy Number Total number of patients having biopsy Total number of patients that re-classified on biopsy (⁎) Number of patients with cancer found in the TZ Number of patients that had re-classification in the TZ Number of patients that had TZ-only re-classification (#) Biopsy 2 (̂) 622 145 103 (16.6%, 103/622) 58 (9.3%, 58/622) 35 (5.6%, 35/622) Biopsy 3 318 63 43 (13.5%) 23 (7.2%) 16 (5.0%) Biopsy 4 131 21 20 (15.2%) 13 (9.9%) 11 (8.4%) Biopsy 5 42 5 6 (14.3%) 3 (7.1%) 2 (4.8%) Total 172 97 64 ⁎ Re-classification defined as GS > 6, > 50single core involved, number of positive cores > 3. # Number of positive cores not used. (̂) Biopsy 2, otherwise known as the confirmatory biopsy. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e614 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lih-Ming Wong Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Ants Toi Toronto, Canada More articles by this author Alexandre Zlotta Toronto, Canada More articles by this author Narhari Timilshina Toronto, Canada More articles by this author Andrew Evans Toronto, Canada More articles by this author Theo Van der Kwast Toronto, Canada More articles by this author Michael Jewett Toronto, Canada More articles by this author Girish Kulkarni Toronto, Canada More articles by this author Robert Hamilton Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

OBJECTIVE To investigate if prostate biopsy templates with fewer cores can be used during active surveillance (AS) for prostate cancer.METHODS At present, we use an AS protocol template (ASPT) consisting of 13-17 cores. We hypothesize in the setting of known cancer, sextant (6 cores) or standard extended (10-12 cores) templates, could be used with similar effect. We identified patients in our referral institution database (1997-2009) with entry prostate-specific antigen <10 ng/mL, stage <= cT2, Gleason sum <= 6, <= 3 cores positive for cancer, <50% of single core involved, and age <= 75 years (N = 272). Patients fulfilling standard criteria for pathologic reclassification (N = 94) at any follow-up biopsy were selected for evaluation. By mapping tumor location on the pathologic reclassification determining biopsy, hypothetical scenarios of sextant or standard extended templates (SET) were compared with our ASPT and examined for frequency of cancer detection and pathologic reclassification.RESULTS For the 94 patients analyzed, the median number of cores taken was 9.7 (6-22) at baseline and 15 (14-17) for the reclassification biopsy. The median time between baseline and the pathologic reclassification determining biopsy was 15.4 months. Analysis of subgroupings showed that sextant template would identify 84% of cancers and 47.9% of the reclassification events, whereas SET detected 99% of cancers and 81.9% of patients who pathologically reclassified. When only considering Gleason sum >= 7 related progression events, SET found 16.2% less (n = 57) compared with ASPT (n = 68).CONCLUSION When monitoring patients on AS, a 13-17 core template detects more pathologic reclassification than standard sextant (18.1%) or extended (52.1%) biopsy templates. UROLOGY 82: 405-409, 2013. (C) 2013 Elsevier Inc.

You have accessJournal of UrologyProstate Cancer: Localized (II)1 Apr 2013549 EXTERNAL DIAGNOSTIC PROSTATE BIOPSY IN ACTIVE SURVEILLANCE: A PREDICTOR OF RE-CLASSIFICATION ON CONFIRMATORY BIOPSY Lih-Ming Wong, Sarah Ferrara, Andrew Evans, Theo Van der Kwast, Greg Trottier, Narhari Timilshina, Ants Toi, John Trachtenberg, Girish Kulkarni, Robert Hamilton, Alexandre Zlotta, Neil Fleshner, and Antonio Finelli Lih-Ming WongLih-Ming Wong Toronto, Canada More articles by this author , Sarah FerraraSarah Ferrara Toronto, Canada More articles by this author , Andrew EvansAndrew Evans Toronto, Canada More articles by this author , Theo Van der KwastTheo Van der Kwast Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Narhari TimilshinaNarhari Timilshina Toronto, Canada More articles by this author , Ants ToiAnts Toi Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , Girish KulkarniGirish Kulkarni Toronto, Canada More articles by this author , Robert HamiltonRobert Hamilton Toronto, Canada More articles by this author , Alexandre ZlottaAlexandre Zlotta Toronto, Canada More articles by this author , Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author , and Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1945AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In active surveillance (AS) for prostate cancer, we examine if having an externally performed diagnostic biopsy, compared to an in-house biopsy, predicts re-classification on the 2nd, otherwise known as the confirmatory, biopsy (B2). METHODS We identified patients on AS from the database of our tertiary care referral centre (1997-2012) with PSA <20, Gleason sum (GS) ≤6, stage T1c, ≤3 positive cores (PCore) for cancer, <50% of single core involved, age≤75y years and a repeat biopsy within 48 months after the initial biopsy. Patients were dichotomized on the basis of where their diagnostic biopsy (B1) was performed to internal (in-house) or external. All externally taken biopsies were reported externally. For all patients, B2 was performed internally. Comparison of the internal and external groups, examining both B1 and B2, were made using the Mann-Whitney U and chi-squared tests. Logistical regression was used to assess if having the B1 performed externally was a predictor of re-classification at B2. RESULTS A total of 649 patients were included, divided into external (n=138) and internal biopsy groups (n=511). Baseline age, PSA and prostate volume were similar between the groups. At baseline, patients with externally taken biopsies had more HGPIN (p=0.01) and ASAP (p=0.001) diagnosed, and less identification of TRUS nodules (p=0.001). The total number of cores taken at B1 was not statistically different between internal and external biopsy groups (p=0.07), however the internal group tended to have more cores taken. At B2, patients with external B1, compared to internal, had increases in all 3 pathological re-classification criteria: GS≥7 (24.6% versus 11.6%, p=0.001), PCore >3 (23% versus 11.7%, p=0.001) and highest % core involved ≥50% (18.5% versus 8.3%, p=0.006). They were also more likely to have a TRUS nodule seen on B2 (45.5% versus 32.5%, p=0.003). Predictors of re-classification at B2 are shown in Table 1. CONCLUSIONS At our institution, patients who had their initial diagnostic prostate biopsy performed externally are more likely to have adverse pathological features and re-classify on internal re-biopsy. Given these findings, this group of patients could be prioritized for earlier confirmatory biopsy. Table 1. Predictors of re-classification at B2 Grade re-classification (GS>=7) Volume re-classification (PCore >3 and/or >50% single core involved) external biopsy OR 2.86 (1.37-5.88), p=0.001 external biopsy OR 2.08 (1.09-4.0), p=0.03 PSA density OR 2.91 (1.66-5.08), p=0.001 PSA density OR 2.15 (1.33-3.47), p=0.002 age OR 1.09 (1.04-1.15), p=0.001 maximum% core involvement OR 1.05 (1.01-1.09), for every unit increase, p=0.009 * Number of cores at baseline biopsy was not predictive of reclassification. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e225-e226 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lih-Ming Wong Toronto, Canada More articles by this author Sarah Ferrara Toronto, Canada More articles by this author Andrew Evans Toronto, Canada More articles by this author Theo Van der Kwast Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Narhari Timilshina Toronto, Canada More articles by this author Ants Toi Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Girish Kulkarni Toronto, Canada More articles by this author Robert Hamilton Toronto, Canada More articles by this author Alexandre Zlotta Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prostatic adenocarcinoma is an epithelial malignancy characterized by marked histological heterogeneity. It most often has a multifocal distribution within the gland, and different Gleason grades may be present within different foci. Data from our group and others have shown that the genomic deletion of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene and the disruption of the ETS gene family have a central role in prostate cancer and are likely to be associated with Gleason grade. In this study, prostate cancer samples were systematically analyzed to determine whether there was concordance between PTEN losses and TMPRSS2–ERG fusion rearrangements, within or between foci in multifocal disease, using well-annotated tissue microarrays (TMAs) consisting of 724 cores derived from 142 radical prostatectomy specimens. Three-color fluorescence in situ hybridization analysis of both the PTEN deletion and the TMPRSS2–ERG fusion was used to precisely map genetic heterogeneity, both within and between tumor foci represented on the TMA. PTEN deletion was observed in 56 of 134 (42%) patients (hemizygous=42 and homozygous=14). TMPRSS2–ERG fusion was observed in 63 of 139 (45%) patients. When analyzed by Gleason pattern for a given TMA core, PTEN deletions were significantly associated with Gleason grades 4 or 5 over grade 3 (P<0.001). Although TMPRSS2–ERG fusions showed a strong relationship with PTEN deletions (P=0.007), TMPRSS2–ERG fusions did not show correlation with Gleason grade. The pattern of genetic heterogeneity of PTEN deletion was more diverse than that observed for TMPRSS2–ERG fusions in multifocal disease. However, the marked interfocal discordance for both TMPRSS2–ERG fusions and PTEN deletions was consistent with the concept that multiple foci of prostate cancer arise independently within the same prostate, and that individual tumor foci can have distinct patterns of genetic rearrangements.

OBJECTIVE To evaluate the associations between body mass index (BMI) and prostate volume (PV) and lower urinary tract symptoms in a multiethnic cohort.METHODS A cohort of men without prostate cancer seen at our institution was assembled, excluding those with previous transurethral resection of the prostate. Height and weight were measured to compute BMI, PV was measured by transrectal ultrasound, and the International Prostate Symptom Score (IPSS) questionnaire was administered. After stratified bivariate analyses, multiple linear regression and ordinal logistic regression models were used to assess the independent effect of BMI on PV and IPSS, respectively.RESULTS The cohort included 1613 patients, and mean BMI was 27.1 kg/m(2). Patients with a BMI of < 25.0, 25.0-29.9, and 30.0-34.9 had a median PV of 44.0 mL, 48.0 mL, and 52.0 mL, respectively. The African ethnicity subgroup generally had larger median PVs than European and Asian subgroups and had the largest differences in median PV between normal and obese men. There were no significant differences in IPSS or usage of benign prostatic hyperplasia medications between BMI categories. In multivariable analyses, higher BMI was associated with larger PV (P <.001) but not IPSS (P = .91). On the basis of our model, given a PV of 40 mL, 50 mL, and 60 mL, each 5 kg/m(2) increase in BMI was associated with a 2.19 mL, 2.74 mL, and 3.29 mL increase in PV, respectively. Body weight (P <.001) but not height (P = .13) was associated with PV.CONCLUSION Higher BMI is associated with larger PV but not worse lower urinary tract symptoms (measured using IPSS). Usage rate of alpha blockers or 5 alpha reductase inhibitors was not significantly different between BMI categories. (C) 2014 Elsevier Inc.

You have accessJournal of UrologyProstate Cancer: Detection and Screening V1 Apr 20122202 PREDICTORS OF FAILING ACTIVE SURVEILLANCE ON THE SECOND PROSTATIC BIOPSY Lih-Ming Wong, Greg Trottier, Ants Toi, Neil Fleshner, John Trachtenberg, Nathan Lawrentschuk, Girish Kulkarni, Narhari Timilshina, and Antonio Finelli Lih-Ming WongLih-Ming Wong Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Ants ToiAnts Toi Toronto, Canada More articles by this author , Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , Nathan LawrentschukNathan Lawrentschuk Melbourne, Australia More articles by this author , Girish KulkarniGirish Kulkarni Toronto, Canada More articles by this author , Narhari TimilshinaNarhari Timilshina Toronto, Canada More articles by this author , and Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2377AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Active surveillance (AS) is a popular method to minimize the morbidity associated with overtreatment of prostate cancer. The rate of patients who progress by grade/volume is reported as 9-35%. We examine factors from the 2nd biopsy, whilst on AS, that may predict pathological progression and need for subsequent therapy. METHODS We identified patients from our prospectively maintained, single academic institution, database with PSA <20, Gleason sum (GS) ≤6, stage T1c, ≤ 3 cores positive for cancer, <50% of single core involved, age ≤75y years and had a repeat biopsy within 48 months after the initial biopsy (n=312). Logistical regression was performed on available data (n=278) to identify predictors of pathological progression, which was defined as GS ≥7, > 3 positive cores and > 50% tumor involvement of any single core. RESULTS Of the 278 patients included, 48 patients had pathological progression on 2nd biopsy and 264 did not. For both groups, median number of biopsy cores taken at 2nd biopsy was the same (n=15). Predictors of pathological progression found were PSA velocity (for every 1 unit increase, OR 1.12 (1.03-1.21), p=0.01), total number of cores taken at first biopsy <10 (OR 2.78 (1.2-6.67), p=0.02), and time between 1st and 2nd biopsies (for every 1 month increase, OR 1.05 (1.02-1.08), p=0.002). CONCLUSIONS We have identified predictors of progression for patients on AS. Patients who had <10 cores on initial biopsy should have confirmatory biopsy to avoid under-sampling. Delay in 2nd biopsy should be avoided and rapid PSAV should trigger early re-biopsy. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e888 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lih-Ming Wong Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Ants Toi Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Nathan Lawrentschuk Melbourne, Australia More articles by this author Girish Kulkarni Toronto, Canada More articles by this author Narhari Timilshina Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

INTRODUCTION AND OBJECTIVES: 5-alpha reductase inhibitors (5ARIs) have been shown to prevent prostate cancer in two large randomized controlled trials. No prior work has shown the effect of 5ARIs on those already diagnosed with low risk prostate cancer. Our goal was to determine the effect of 5ARIs on pathologic progression in men on active surveillance for prostate cancer. METHODS: This was a single institution retrospective cohort study comparing men taking a 5ARI versus no 5ARI while on active surveillance for prostate cancer. All men had at least two biopsies. Inclusion criteria for active surveillance were PSA 10 ng/ml, clinical stage T1c/T2a, Gleason score 6, and 3 cores positive with no more than 50% of a core involved at initial diagnostic biopsy. Pathologic progression was evaluated and defined as Gleason score 6, or maximum core involvement 50% or 3 cores positive on a follow-up prostate biopsy. Univariate, multivariate and Kaplan-Meir analyses were conducted. RESULTS: A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 months (IQR 23.6– 59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%, p 0.004) and were less likely to abandon active surveillance (20% vs 37.6%, p 0.006). The median time to progression was longer in the 5ARI group (42.5 months) compared to the non-5ARI group (31.5 months; p 0.026). On multivariate analysis, lack of 5ARI use was most strongly associated with pathologic progression (OR 2.98, 95% CI 1.5–5.9) followed by age and baseline maximum percentage involvement of any biopsy core. CONCLUSIONS: 5ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.

Purpose: The effects of partial nephrectomy (PN) on postoperative blood pressure (BP) are not known, and PN has the potential to worsen BP. We therefore sought to determine whether PN alters postoperative BP.Materials and Methods: Patients who underwent PN for suspected malignancy at our institution from 2002 to 2008 were included. Data on BP and medication from before and after PN were retrieved from family physicians. BP and number of antihypertensive medications were compared after surgery with preoperative values by use of paired t tests and Chi-squared analyses, respectively.Results: Of 74 patients undergoing PN and providing consent, 48 met the inclusion and exclusion criteria, with a median follow-up of 24 months. For the early postoperative period (1 month to 1 year after surgery), the mean BPs (132.3/77.0 mmHg) were unchanged compared with preoperative values (132.4/78.0 mmHg; p=0.59 systolic BP and p=0.30 diastolic BP). For the later postoperative period (beyond 1 year after surgery), the mean postoperative systolic BP was unchanged from the mean preoperative systolic BP (131.2 mmHg vs. 132.4 mmHg, respectively; p>0.30). However, the corresponding average diastolic BP was lower in the long term (78.0 mmHg versus 76.4 mmHg respectively; p=0.01). No significant difference in the mean number of BP medications prescribed preoperatively, at one year, and beyond one year was identified (p>0.37).Conclusions: PN does not result in initial or long-term postoperative deterioration in BP.

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20122235 SERUM ADIPOKINE LEVELS IMPROVE PROSTATE CANCER PREDICTION COMPARED TO CLINICAL DATA ONLY David Margel, Greg Trottier, Stanley Yap, Malik Elharram, Mike Connor, Bimal Bhindi, Antonio Finelli, Girish Kulkarny, and Neil Fleshner David MargelDavid Margel Toronto, Canada More articles by this author , Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Stanley YapStanley Yap Toronto, Canada More articles by this author , Malik ElharramMalik Elharram Toronto, Canada More articles by this author , Mike ConnorMike Connor Toronto, Canada More articles by this author , Bimal BhindiBimal Bhindi Toronto, Canada More articles by this author , Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author , Girish KulkarnyGirish Kulkarny Toronto, Canada More articles by this author , and Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2411AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In a previous study we demonstrated the potential of Adipokines (cytokine hormones released from adipocytes) as biomarkers for prostate cancer. However biomarkers are costly and should only be used clinically if they prove superior to existing models using clinical data. In this study we sought to determine whether these novel biomarkers offer additional diagnostic benefit in comparison to the use of clinical data alone. METHODS The analysis included data from 200 patients undergoing TRUS guided prostate biopsy at a single center. One-hundred PCa cases and 100 controls were chosen with an even mix of patients having a body mass indexes (BMI) above and below 27 kg/m2. Serum samples collected prior to prostate biopsy were used to measure adipokines (adiponectin, leptin, PAI, Resistin, HGF, IL-1 alfa, IL-6, IL-8, MCP-1, NGF and TNF-alfa) using Milliplex Multi-Analyte Profiling kits (Adipokine panels A and B; Millipore; Billerica, MA, USA). Multivariable models for predicting prostate cancer and high grade prostate cancer were created using predictors from three model selection methods (Forward, Backward, Stepwise) based on 1000 bootstrap samples. We compared a model composed of clinical data to one that includes both clinical data and serum adipokine levels. The ability of each model to predict PCa outcome was evaluated by area under the receiver operating characteristic curve (AUC of ROC). RESULTS The multivariable clinical model to predict prostate cancer included the following variables: Digital rectal examination, BMI, previous negative biopsy and PSA. The adipokine multivariable model included these clinical variables and the levels of the following adipokines: MCP-1, TNF alfa, IL-6 and HGF. The AUC of the ROC curve for predicting prostate cancer was 0.67 (95%CI 0.59-0.74) for the clinical data only vs. 0.745 (95%CI 0.67-0.81) for the model including adipokines (p=0.018). The clinical model to predict high grade prostate cancer included: DRE, PSA and previous biopsy. The adipokines added to predict high grade cancers were: NGF and MCP-1. The AUC of the ROC curve for predicting high grade prostate cancer was 0.75 (95%CI 0.67-0.83) for the clinical data only vs. 0.79 (95%CI 0.71-0.86) for the model including adipokines (p=0.0532). CONCLUSIONS We have demonstrated that adding serum adipokine levels increases the accuracy of models predicting both prostate cancer and high grade prostate cancer. The results of this study require further validation using a larger multi-center cohort. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e901-e902 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Margel Toronto, Canada More articles by this author Greg Trottier Toronto, Canada More articles by this author Stanley Yap Toronto, Canada More articles by this author Malik Elharram Toronto, Canada More articles by this author Mike Connor Toronto, Canada More articles by this author Bimal Bhindi Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author Girish Kulkarny Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

UNLABELLED:Study Type - Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? ADIPOSE tissue secretes various endocrine and paracrine mediators. Some authors have begun to consider whether peri-prostatic fat (PPF) may interact with the prostate and play a role in carcinogenesis. It has recently been shown that the PPF quantity measured by CT is associated with more aggressive disease in patients undergoing radiation therapy. Our group studied a population not yet diagnosed with prostate cancer. By doing so we were able to identify PPF thickness on transrectal ultrasonography as a risk factor for prostate cancer detection upon biopsy, and as a risk factor for high-grade disease. Our study also raises interesting questions about the underlying mechanisms of the association between PPF quantity and prostate cancer.OBJECTIVE:To determine if the amount of peri-prostatic fat (PPF) on transrectal ultrasonography (TRUS) is a risk factor for incident prostate cancer overall and high-grade prostate cancer (Gleason ≥4).PATIENTS AND METHODS:A prospectively maintained database of patients undergoing prostate biopsy at Princess Margaret Hospital for cancer suspicion was used. • All TRUS examinations were retrospectively reviewed upon 'blinding' to outcome. • PPF thickness, measured as the distance between the prostate and the pubic bone, was used as an index of the quantity of PPF. • PPF measurements, together with other prostate cancer risk factors, were evaluated against prostate cancer and high-grade prostate cancer detection upon biopsy with univariable and multivariable logistic regression and area under the receiver operating characteristic curve (AUC) analysis.RESULTS:Of the 931 patients, 434 (47%) were diagnosed with prostate cancer and 218 (23%) were diagnosed with high-grade prostate cancer. • The mean (range) PPF thickness was 5.3 (0-15) mm. • Increasing PPF thickness was associated with prostate cancer and high-grade prostate cancer diagnosis, with graded effect. When adjusting for other variables, the odds of detecting any prostate cancer and high-grade prostate cancer increased 12% (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23) and 20% (OR 1.20, 95% CI 1.07-1.34), respectively, for each millimetre increase in PPF thickness. • The AUCs for the association of PPF with prostate cancer and high-grade prostate cancer were 0.58 (95% CI 0.54-0.62) and 0.59 (95% CI 0.55-0.64), respectively.CONCLUSION:The amount of PPF can be estimated with TRUS and is a predictor of prostate cancer and high-grade prostate cancer at biopsy. To our knowledge, this study is the first to investigate PPF quantity in patients without prior prostate cancer diagnosis.

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112331 ASSOCIATION OF ADIPOKINES WITH PROSTATE CANCER AND HIGH GRADE DISEASE DEPENDS ON BODY MASS INDEX Greg Trottier, Michael K. Connor, Jordan Zeppieri, David Margel, Kimberly A. Fernandes, Antonio Finelli, Andrew Evans, Theodorus H. van der Kwast, Ants Toi, Karen Hersey, and Neil E. Fleshner Greg TrottierGreg Trottier Toronto, Canada More articles by this author , Michael K. ConnorMichael K. Connor Toronto, Canada More articles by this author , Jordan ZeppieriJordan Zeppieri Toronto, Canada More articles by this author , David MargelDavid Margel Toronto, Canada More articles by this author , Kimberly A. FernandesKimberly A. Fernandes Toronto, Canada More articles by this author , Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author , Andrew EvansAndrew Evans Toronto, Canada More articles by this author , Theodorus H. van der KwastTheodorus H. van der Kwast Toronto, Canada More articles by this author , Ants ToiAnts Toi Toronto, Canada More articles by this author , Karen HerseyKaren Hersey Toronto, Canada More articles by this author , and Neil E. FleshnerNeil E. Fleshner Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2578AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diet and obesity are associated with prostate cancer (PCa). We set out to determine if a group of serum adipokines were associated with PCa or high grade (HG) disease at biopsy. METHODS Prospectively collected serum specimens from the GU Biobank at the Princess Margaret Hospital were utilized. From this biobank, 50 patients with Gleason 6 PCa, 50 patients with HG Gleason ≥7 PCa and 100 patients with negative biopsies were randomly chosen in a case-control fashion. For each group 50% of patients were chosen with a BMI ≤27 and 50% were chosen with a BMI >27. A panel of 11 adipokines (Adiponectin, leptin, PAI, Resistin, HGF, IL-1beta, IL-6, IL-8, MCP1, NGF, TNF alpha) were assayed from each patient. Association of adipokines with PCa or HG PCa was evaluated by receiver operating characteristic curve (ROC)/area under the curve (AUC) analysis and univariate logistic regression (LR). RESULTS This patient cohort had a median PSA of 5.8 ng/ml, a median age of 62 years and a median BMI of 27.2 kg/m2. None of the adipokines correlated with BMI except leptin (p<0.01). There were no significant correlations between individual adipokines. ROC analysis showed that Resistin (AUC 0.64; 95% CI 0.5–0.74) and MCP-1 (AUC 0.61; 95% CI 0.49–0.72) were the top ranked markers for discriminating cancer from no cancer among those with a BMI ≤27. In those with a BMI >27, IL-1 beta (AUC 0.61; 95% CI 0.49–0.72) and IL-6 (AUC 0.61; 95% CI 0.49–0.70); displayed the best discrimination. In the case of HG disease, NGF (AUC 0.69; 95% CI 0.57–0.81) and IL-1 beta (AUC 0.66; 95% CI 0.54–0.78) were most predictive among those with a BMI >27, while neither were predictive in the lower BMI group. Conversely, MCP-1 (AUC 0.61; 95% CI 0.47–0.73) and adiponectin (AUC 0.60; 95% CI 0.45–0.74) demonstrated the highest discrimination among those with a BMI ≤27. Using LR, only MCP-1 (OR 1.83, p=0.05) was associated with PCa among the low BMI group, while none of the markers were significant in the high BMI group. By contrast, NGF (OR 2.61; p=0.01) and IL-1 beta (OR 2.46; p=0.03) maintained an association with HG disease among the high BMI group, with none of the markers being significant in the lower BMI group. CONCLUSIONS Several adipokines demonstrate potential as predictive markers of PCa when BMI stratified. Of note, NGF was the only adiopkine with selective discrimination for HG PCa. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e934-e935 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Greg Trottier Toronto, Canada More articles by this author Michael K. Connor Toronto, Canada More articles by this author Jordan Zeppieri Toronto, Canada More articles by this author David Margel Toronto, Canada More articles by this author Kimberly A. Fernandes Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author Andrew Evans Toronto, Canada More articles by this author Theodorus H. van der Kwast Toronto, Canada More articles by this author Ants Toi Toronto, Canada More articles by this author Karen Hersey Toronto, Canada More articles by this author Neil E. Fleshner Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...