High-grade Prostate Cancer In Men Research Articles

A urine-based Exosomal gene expression test stratifies risk of high-grade prostate Cancer in men with prior negative prostate biopsy undergoing repeat biopsy

BackgroundInitial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate (IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established.MethodsAs part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2–10 ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results.Results229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35 and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.ConclusionsThe EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2–10 ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.

50 - Use of a urine exosome RNA test to assess risk of high-grade prostate cancer in men with a prior negative biopsy

50 - Use of a urine exosome RNA test to assess risk of high-grade prostate cancer in men with a prior negative biopsy

Omega-3 Fatty Acids Survey in Men under Active Surveillance for Prostate Cancer: from Intake to Prostate Tissue Level.

Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ω3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LCω3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08–0.79; p-trend = 0.03) was associated with lower odds of high-grade PCa. Similar results were observed for LCω3 dietary intake (OR 0.30; 95% CI 0.11-0.83; p-trend = 0.02) but no association for RBC. LCω3-EPA levels in the target prostate tissue are inversely associated with high-grade PCa in men with low-risk PCa, supporting that prostate tissue FA, but not RBC FA, is a reliable biomarker of PCa risk.

Periprostatic fat adipokine expression is correlated with prostate cancer aggressiveness in men undergoing radical prostatectomy for clinically localized disease.

To investigate the relationship between periprostatic adipose tissue (PPAT) adipokine expression and prostate cancer (PCa) aggressiveness using both pathological features of radical prostatectomy (RP) and multiparametric magnetic resonance imaging ( MRI) variables. Sixty-nine men were recruited to assess immunohistochemical expression of tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) of periprostatic fat of RP specimens. Per cent immunopositivity was quantified on scanned slides using the Aperio Positive Pixel Count algorithm for PPAT TNFα, VEGF and androgen receptors. Periprostatic fat volume (PFV) was segmented on contiguous T1 -weighted axial MRI slices from the level of the prostate base to apex. PFV was normalized to prostate volume (PV) to account for variations in PV (normalized PFV = PFV/PV). MRI quantitative values (Kep , Ktrans and apparent diffusion coefficient) were measured from the PCa primary lesion using Olea Sphere software. Patients were stratified into three groups according to RP Gleason score (GS): ≤6, 7(3 + 4) and ≥7(4 + 3). The mean rank of VEGF and TNFα was significantly different between the groups [H(2) = 11.038, P = 0.004] and [H(2) = 13.086, P = 0.001], respectively. Patients with stage pT3 had higher TNFα (18.2 ± 8.95) positivity than patients with stage pT2 (13.27 ± 10.66; t [67] = -2.03, P = 0.047). TNFα expression significantly correlated with Ktrans (ρ = 0.327, P = 0.023). TNFα (P = 0.043), and VEGF (P = 0.02) correlated with high grade PCa (GS ≥ 7) in RP specimens and also correlated significantly with upgrading of GS from biopsy to RP histology. The expression levels of TNFα and VEGF on immunostaining significantly correlated with aggressivity of PCa. As biomarkers, these indicate the risk of having high grade PCa in men undergoing RP.

Is magnetic resonance imaging-targeted biopsy a useful addition to systematic confirmatory biopsy in men on active surveillance for low-risk prostate cancer? A systematic review and meta-analysis.

To systematically review and meta-analyse evidence regarding the additional value of magnetic resonance imaging (MRI) and MRI-targeted biopsies to confirmatory systematic biopsies in identifying high-grade prostate cancer in men with low-risk disease on transrectal ultrasonography (TRUS) biopsy, as active surveillance (AS) of prostate cancer is recommended for men with Gleason 3 + 3 on standard TRUS-guided biopsy. Confirmatory assessment can include repeat standard TRUS-guided biopsy, and/or MRI with targeted biopsy when indicated. A systematic review of the Embase, Medline, Web-of-science, Google scholar, and Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 criteria. Studies reporting men with Gleason 3 + 3 prostate cancer who had chosen AS based on transrectal systematic biopsy findings and had undergone MRI with systematic ± targeted biopsy at confirmatory assessment were included. The primary outcome was detection of any Gleason pattern ≥4. Included reports (six) of men on AS (n = 1 159) showed cancer upgrading (Gleason ≥3 + 4) in 27% (95% confidence interval [CI] 22-34%) using a combined approach of MRI-targeted biopsies and confirmatory systematic biopsies. MRI-targeted biopsies alone would have missed cancer upgrading in 10% (95% CI 8-14%) and standard biopsies alone would have missed cancer upgrading in 7% (95% CI 5-10%). No pathway was more favourable than the other (relative risk [RR] 0.92, 95% CI 0.79-1.06). In all, 35% (95% CI 27-43%) of men with a positive MRI were upgraded, compared to 12% (95% CI 8-18%) of men with a negative MRI being upgraded (RR 2.77, 95% CI 1.76-4.38). A pre-biopsy MRI should be performed before confirmatory systematic TRUS-guided biopsies in men on AS, together with MRI-targeted biopsies when indicated. A combined approach maximises cancer detection, although other factors within multivariate risk prediction can be used to aid the decision to biopsy in these men.

265P - Multi-parametric magnetic resonance imaging-based nomogram for predicting prostate cancer and high-grade prostate cancer in men undergoing repeat prostate biopsy

265P - Multi-parametric magnetic resonance imaging-based nomogram for predicting prostate cancer and high-grade prostate cancer in men undergoing repeat prostate biopsy

Abstract 1251: Pioglitazone inhibits periprostatic white adipose tissue inflammation in obese mice

Abstract Obesity is associated with an increased incidence of high-grade prostate cancer (PC) and poor prognosis for PC patients. Recently, we showed that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by crown-like structures (CLS) consisting of dead or dying adipocytes surrounded by macrophages, was associated with high-grade PC in men. It’s possible, therefore, that agents that suppress periprostatic WAT inflammation will alter the natural history of PC. Pioglitazone, a ligand of PPARγ, is used to treat diabetes and possesses anti-inflammatory properties. Here our main objectives were to determine if pioglitazone inhibited obesity-related periprostatic WAT inflammation in mice and then to elucidate the underlying mechanism. Mice were fed either a high fat (HF) diet or low fat (LF) diet to determine if obesity caused periprostatic WAT inflammation as defined by the presence of CLS. To determine if pioglitazone inhibited obesity-associated periprostatic WAT inflammation, obese HF diet fed mice were either continued on HF diet alone or treated with HF diet containing two doses (0.005% or 0.05% w/w) of pioglitazone. Treatment with pioglitazone reduced the density of CLS in periprostatic WAT, and suppressed levels of TNF-α, TGF-β and the chemokine monocyte chemoattractant protein-1 (MCP-1). Importantly, the ability of pioglitazone to suppress periprostatic WAT inflammation was abrogated in MCP-1 knock out mice. Pioglitazone caused dose-dependent induction of both adiponectin, an anti-inflammatory adipokine, and its receptor AdipoR2 in cultured 3T3-L1 cells and in periprostatic WAT of obese mice. Pioglitazone blocked TNF-α-mediated induction of MCP-1 in 3T3-L1 cells, an effect that was attenuated when either adiponectin or AdipoR2 were silenced. Taken together, pioglitazone-mediated induction of adiponectin suppressed the elevation in MCP-1 levels thereby attenuating obesity-related periprostatic WAT inflammation. These findings strengthen the rationale for future efforts to determine whether targeting the PPARγ-adiponectin-MCP-1 axis will decrease periprostatic adipose inflammation and thereby reduce the risk of high-grade PC or improve outcomes for men with PC. Citation Format: Miki Miyazawa, Kotha Subbaramaiah, Priya Bhardwaj, Xi Kathy Zhou, Hanhan Wang, Domenick J. Falcone, Dilip D. Giri, Andrew J. Dannenberg. Pioglitazone inhibits periprostatic white adipose tissue inflammation in obese mice [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 1251. doi:10.1158/1538-7445.AM2017-1251

Evaluating the Four Kallikrein Panel of the 4Kscore for Prediction of High-grade Prostate Cancer in Men in the Canary Prostate Active Surveillance Study

BackgroundDiagnosis of Gleason 6 prostate cancer can leave uncertainty about the presence of undetected aggressive disease. ObjectiveTo evaluate the utility of a four kallikrein (4K) panel in predicting the presence of high-grade cancer in men on active surveillance. Design, setting, and participantsPlasma collected before the first and subsequent surveillance biopsies was assessed for 718 men prospectively enrolled in the multi-institutional Canary PASS trial. Biopsy data were split 2:1 into training and test sets. We developed statistical models that included clinical information and either the 4Kpanel or serum prostate-specific antigen (PSA). Outcome measurements and statistical analysisThe endpoint was reclassification to Gleason ≥7. We used receiver operating characteristic (ROC) curve analyses and area under the curve (AUC) to assess discriminatory capacity, and decision curve analysis (DCA) to report clinical net benefit. Results and limitationsSignificant predictors for reclassification were 4Kpanel (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31–1.81) or PSA (OR 2.11, 95% CI 1.53–2.91), ≥20% cores positive (OR 2.10, 95% CI 1.33–3.32), two or more prior negative biopsies (OR 0.19, 95% CI 0.04–0.85), prostate volume (OR 0.47, 95% CI 0.31–0.70), and body mass index (OR 1.09, 95% CI 1.04–1.14). ROC curve analysis comparing 4K and base models indicated that the 4Kpanel improved accuracy for predicting reclassification (AUC 0.78 vs 0.74) at the first surveillance biopsy. Both models performed comparably for prediction of reclassification at subsequent biopsies (AUC 0.75 vs 0.76). In DCA, both models showed higher net benefit compared to biopsy-all and biopsy-none strategies. Limitations include the single cohort nature of the study and the small numbers; results should be validated in another cohort before clinical use. ConclusionsThe 4Kpanel provided incremental value over routine clinical information in predicting high-grade cancer in the first biopsy after diagnosis. The 4Kpanel did not add predictive value to the base model at subsequent surveillance biopsies. Patient summaryActive surveillance is a management strategy for many low-grade prostate cancers. Repeat biopsies monitor for previously undetected high-grade cancer. We show that a model with clinical variables, including a panel of four kallikreins, indicates the presence of high-grade cancer before a biopsy is performed.

The association between race and prostate cancer risk on initial biopsy in an equal access, multiethnic cohort.

Population-based studies have established a link between race and prostate cancer (PC) risk, but whether race predicts PC after adjusting for clinical characteristics is unclear. We investigated the association between race and risk of low- and high-grade PC in men undergoing initial prostate biopsy in an equal access medical center. We conducted a retrospective record review of 887 men (48.6 % black, 51.4 % white) from the Durham Veterans Affairs Medical Center who underwent initial prostate biopsy between 2001 and 2009. Multivariable logistic regression analysis of race and biopsy outcome was conducted adjusting for age, body mass index, number of cores taken, prostate-specific antigen (PSA), and digital rectal examination findings. Multinomial logistic regression was used to test the association between black race and PC grade (Gleason <7 vs. ≥7). Black men were younger at biopsy (61 vs. 65 years, p < 0.001) and had a higher pre-biopsy PSA (6.6 vs. 5.8 ng/ml, p = 0.001). A total of 499 men had PC on biopsy (245 low grade; 254 high grade). In multivariable analyses, black race was significantly predictive of PC overall [odds ratio 1.50, p = 0.006] and high-grade PC [relative risk ratio (RRR) 1.84, p = 0.001], but was not significantly associated with low-grade PC (RRR 1.29, p = 0.139). In an equal access healthcare facility, black race was associated with greater risk of PC detection on initial biopsy and of high-grade PC after adjusting for clinical characteristics. Additional investigation of mechanisms linking black race and PC risk and PC aggressiveness is needed.

Agent Orange as a risk factor for high‐grade prostate cancer

Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa) (Gleason score ≥7) on biopsy in a US Veteran cohort. Risk factors included clinicodemographic and laboratory data from veterans who were referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa) (Gleason score ≤6) in biopsy specimens. Risk among AOe veterans relative to unexposed veterans was estimated using multivariate logistic regression. Separate models were used to determine whether AOe was associated with an increased risk of PCa, HGPCa, or LGPCa. Of 2720 veterans who underwent biopsy, PCa was diagnosed in 896 veterans (32.9%), and 459 veterans (16.9%) had HGPCa. AOe was associated with a 52% increase in the overall risk of detecting PCa (adjusted odds ratio, 1.52; 95% confidence interval, 1.07-2.13). AOe did not confer an increase in the risk of LGPCa (adjusted odds ratio, 1.24; 95% confidence interval, 0.81-1.91), although a 75% increase in the risk of HGPCa was observed (adjusted odds ratio, 1.75; 95% confidence interval, 1.12-2.74). AOe was associated with a 2.1-fold increase (95% confidence interval, 1.22-3.62; P < .01) in the risk of detecting PCa with a Gleason score ≥8. The current results indicated that an increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men who undergo an initial prostate biopsy. These findings may aid in improved PCa screening for Vietnam-era veterans.

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

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

Editorial Comment

The holy grail in PCa is to differentiate the relatively small number of tumors that will ultimately cause patient death from the large number of tumors that are unlikely to result in metastatic disease or eventual patient death. A key success factor would be a simple, inexpensive, readily available laboratory test, such as %FT. Albisinni et al provide intriguing findings in this regard. They reported that among 812 Italian men who underwent PCa biopsy, the %FT was increased in Gleason score 7 and greater tumors and neither testosterone nor free testosterone was associated with PCa development. In particular, men in the greatest %FT tertile had a significant twofold increased risk of high-grade PCa (95% CI 1.23-3.37). Although the findings are based on a single-site evaluation, the blood tests and biopsy and pathology protocols were all standardized, although only 1 sample was used to classify the hormonal concentrations. Greater Percent-free Testosterone Is Associated With High-grade Prostate Cancer in Men Undergoing Prostate BiopsyUrologyVol. 80Issue 1PreviewTo analyze the serum androgen concentrations in men who underwent an initial prostate biopsy, focusing on the percent-free testosterone (%FT) as a predictor of low- and high-grade prostate cancer (PCa). Most studies have suggested that the absolute serum testosterone and free testosterone levels are not related to PCa risk. However, to date, the concurrent effect of free and total testosterone levels has not been evaluated. In particular, the association of the %FT (free testosterone/total testosterone) with PCa risk has not been explored. Full-Text PDF

Serum total and HDL cholesterol and risk of prostate cancer.

Studies suggest a decreased risk of high-grade prostate cancer in men with lower circulating total cholesterol and that statins may protect against aggressive disease. Confirmation in additional populations and examination of associations for lipoprotein subfractions are needed. We examined prostate cancer risk and serum total and HDL cholesterol in the ATBC Study cohort (n=29,093). Cox proportional hazards models were used to estimate the relative risk of total (n=2,041), non-aggressive (n=829), aggressive (n=461), advanced (n=412), and high-grade (n=231) prostate cancer by categories of total and HDL cholesterol. After excluding the first 10years of follow-up, men with higher serum total cholesterol were at increased risk of overall (≥240 vs. <200mg/dl: HR=1.22, 95% CI 1.03-1.44, p-trend=0.01) and advanced (≥240 vs. <200mg/dl: HR=1.85, 95% CI 1.13-3.03, p-trend=0.05) prostate cancer. Higher HDL cholesterol was suggestively associated with a decreased risk of prostate cancer regardless of stage or grade. In this population of smokers, high serum total cholesterol was associated with higher risk of advanced prostate cancer, and high HDL cholesterol suggestively reduced the risk of prostate cancer overall. These results support previous studies and, indirectly, support the hypothesis that statins may reduce the risk of advanced prostate cancer by lowering cholesterol.

Diabetes mellitus, race, and the odds of high-grade prostate cancer in men diagnosed with prostate cancer in the United States.

180 Background: African American (AA) men present more frequently with high-grade prostate cancer (PCa) and are also more likely to have diabetes mellitus (DM). We evaluated whether there is an independent association between DM and the risk of high-grade PCa in men diagnosed with PCa, adjusting for the known predictors of high-grade PCa including AA race. Methods: Between 1991 and 2009 15,377 men newly diagnosed with PCa and treated at 1 of 26 centers, were analyzed in 2 cohorts. Multivariable logistic regression was performed to evaluate whether a diagnosis of DM was associated with the odds of Gleason 7 or 8 to 10 PCa, adjusting for AA race, advancing age, PSA level, and DRE findings. Results: AA men (AOR, 1.87; 95% CI, 1.04-3.37, P=0.04) and non-AA men (AOR, 1.61; 95% CI, 1.34-1.93; P&lt;0.001) with diabetes were more likely to have GS 8 to 10 versus GS 6 or less PCa, compared to non-diabetic men. AA as compared to non-AA race was not significantly associated with the odds of having GS 8 to 10 as compared to 6 or less PCa, both in men with a diagnosis of DM (AOR, 1.47; 95% CI, 0.87-2.50; P=0.15) and without DM (AOR, 1.27; 95% CI, 0.92-1.74, P=0.14). AA race, however (AOR, 1.37; 95% CI, 1.17-1.60, P&lt;0.001), but not DM (AOR 1.09; 95% CI, 0.97-1.22, P=0.16), was associated with GS 7 versus 6 or less PCa. Conclusions: A diagnosis of DM is a risk factor for presenting with Gleason 8 to 10 PCa independent of race. [Table: see text] No significant financial relationships to disclose.

Abstract B92: Serum total and HDL cholesterol and risk of prostate cancer

Abstract Background: There has been growing support for the hypothesis that low cholesterol may protect against prostate cancer with a poorer prognosis. Studies suggest a decreased risk of high-grade prostate cancer in men with lower circulating total cholesterol, and that statin drugs may protect against aggressive prostate cancer. Confirmation of these findings in additional populations and examination of lipoprotein subfractions is needed. We prospectively examined prostate cancer risk and serum total and HDL cholesterol in the ATBC Study cohort. Methods: The ATBC Study was a randomized controlled trial conducted among male smokers in Finland to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence. Fasting blood samples were collected at baseline (1985 — 1988), and total and HDL cholesterol were measured for all participants (n=29,133). Cohort follow-up continues through the Finnish Cancer Registry and the Register of Causes of Death. Cox proportional hazards models were used to estimate the relative risk of overall (n=2,041), high stage (≥ TNM stage III or AJC stage 3; n=412), high grade (Gleason sum ≥ 7; n=231), aggressive (either high stage or high grade; n=461), and non-aggressive (neither high stage nor high grade; n=829) prostate cancer by categories of total (&amp;lt;200, 200 — &amp;lt;240, ≥240 mg/dL) and HDL (&amp;lt;40, 40 — &amp;lt;60, ≥60 mg/dL) cholesterol. Multivariable models adjusted for age, serum α-tocopherol, family history of prostate cancer, education, and urban residence. Further adjustment for the following factors did not alter the results: α-tocopherol and β-carotene supplementation group, serum β-carotene, cigarettes per day, years smoked, physical activity, marital status, and intake of total energy, total fat, fruits and vegetables, red meat, alcohol, vitamin A, vitamin D, and calcium. Results: Men with high serum total cholesterol were at increased risk of prostate cancer, particularly high stage disease (≥240 vs. &amp;lt;200 mg/dl: HR=1.26, 95% CI 0.92 — 1.71, p-trend = 0.03). Stratification by follow-up time showed that the increased risk of prostate cancer for men with higher total cholesterol was limited to cases diagnosed at least 10 years after baseline. After excluding the first 9 years of follow-up, men with higher serum total cholesterol were at an increased risk of overall (≥240 vs. &amp;lt;200: HR=1.22, 95% CI 1.03 — 1.44, p-trend=0.01) and advanced-stage (≥240 vs. &amp;lt;200: HR=1.85, 95% CI 1.13 — 3.03, p-trend=0.05) prostate cancer. Higher HDL cholesterol appeared related to decreased risk of prostate cancer, overall and all clinical subtypes, throughout the follow-up period. Conclusion: In this population of male smokers with a low prevalence of PSA screening, high serum total cholesterol was associated with an increased risk of advanced prostate cancer, but only among cases diagnosed at least 10 years after baseline. Further, there was a suggestion that high HDL cholesterol reduced the risk of all clinical subtypes of prostate cancer. These results support previous studies and, indirectly, support the hypothesis that statin drugs may reduce the risk of prostate cancer with a poorer prognosis by lowering cholesterol concentrations. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B92.

Finasteride

Importance of the field: Prostate cancer is the most common non-cutaneous malignancy in males in the US. Prostate cancer chemoprevention entails the use of agents which retard or inhibit the progression to invasive disease. Chemoprevention is an attractive option for patients with prostate cancer given the hormonally responsive nature of cancer, long latency period and high prevalence of the disease.Areas covered in this review: This review outlines a detailed background on the development of finasteride as a chemopreventive agent for prostate cancer. It discusses the Prostate Cancer Prevention Trial, a large randomized clinical trial that showed reduction in prostate cancer prevalence through the use of finasteride. In addition, an in-depth discussion involving theories on a higher incidence of high-grade cancer in the finasteride arm is presented. Other notable recently completed randomized trials and novel chemopreventive agents for prostate cancer are discussed as well.What the reader will gain: Readers will get an in-depth understanding of the balance of risks and benefits of finasteride for prevention of prostate cancer.Take home message: Finasteride was the first 5α-reductase inhibitor to show a benefit in reducing prevalence of prostate cancer. It is well tolerated but a higher incidence of high-grade prostate cancer in men taking finasteride has hindered its use in clinical practice. It may temporarily shrink tumors that have a low potential for being lethal and is not approved as a chemopreventive agent.

Abstract ED02-01: Molecular targets of cancer preventive agents

Abstract ED02-01: Molecular targets of cancer preventive agents

The PCPT: New Findings, New Insights, and Clinical Implications for the Prevention of Prostate Cancer

The Prostate Cancer Prevention Trial (PCPT) demonstrated that finasteride therapy significantly reduced the risk of prostate cancer by 24.8% ( p < 0.001) compared with placebo. Controversially, there was an increased incidence of high-grade (Gleason score ≥ 7) tumours in the finasteride arm compared with placebo. The increase in incidence of high-grade disease observed in finasteride-treated subjects does not appear to be a histopathologic effect. A number of potential biases have been identified, including increased detection rate due to prostate volume reduction and improved prostate-specific antigen specificity and sensitivity for detecting prostate cancer. This would suggest that there was an improved detection of overall prostate cancer as well as high-grade prostate cancer in men treated with finasteride, rather than an increase in risk compared with placebo. Further analyses of the data from the PCPT together with other clinical findings strongly suggest that the increase in high-grade tumours in the finasteride arm is an artefact.