Change In Serum Prostate-specific Antigen Research Articles

Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor)

BackgroundThe prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs)....

Vitamin D, a Regulator of Androgen Levels, Is Not Correlated to PSA Serum Levels in a Cohort of the Middle Italy Region Participating to a Prostate Cancer Screening Campaign.

Prostate cancer (PCa) is the most common non-cutaneous malignancy in men worldwide, and it represents the fifth leading cause of death. It has long been recognized that dietary habits can impact prostate health and improve the benefits of traditional medical care. The activity of novel agents on prostate health is routinely assessed by measuring changes in serum prostate-specific antigen (PSA) levels. Recent studies hypothesized that vitamin D supplementation reduces circulating androgen levels and PSA secretion, inhibits cell growth of the hormone-sensitive PCa cell lines, counteracts neoangiogenesis and improves apoptosis. However, the results are conflicting and inconsistent. Furthermore, the use of vitamin D in PCa treatments has not achieved consistently positive results to date. In order to assess the existence of a correlation between the PSA and 25(OH)vitamin D levels as widely hypothesized in the literature, we analyzed the serum PSA and 25(OH)vitamin D concentration on a cohort of one hundred patients joining a PCa screening campaign. Additionally, we performed medical and pharmacological anamnesis and analyzed lifestyle, as sport practice and eating habits, by administering a questionnaire on family history. Although several studies suggested a protective role of vitamin D in PCa onset prevention and progression, our preliminary results revealed a clear absence of correlation between the serum vitamin D and PSA concentration levels, suggesting that vitamin D has no impact on PCa risk. Further investigations enrolling a huge number of patients are needed with particular attention to vitamin D supplementation, calcium intake, solar radiation that influences vitamin D metabolism and other potential indicators of health to confirm the absence of correlation observed in our study.

Prostate volume is an independent predictive factor in selecting low-risk prostate patients for active surveillance

PurposeThe outcome of the present study is to determine variables available at the time of diagnosis able to predict disease reclassification in prostate cancer (PCa) patients on active surveillance (AS).Materials and methodsFrom January 2014 to December 2018, 114 consecutive low-risk PCa patients were enrolled in AS protocol according to inclusion criteria: PSA ≤ 10 ng/ml, Gleason score (GS) ≤ 6 or International Society of Urological Pathology (ISUP) Gleason grade group (GG) 1, maximum cancer core length (MCCI) < 50%, and ≤ 2 positive cores on biopsy. Patients were followed with confirmatory and yearly prostate biopsy, semi-annually with prostate-specific antigen (PSA), and digital rectal examination (DRE). Disease reclassification was defined as upgrading biopsy: GS ≥ 3 + 4 = 7 or ISUP GG ≥ 2, more than two positive cores, MCCI > 50%, or changes in serum PSA > 10 ng/ml. Uni- and multivariate Cox proportional hazards regression models, receiver performance curves (ROC), and Kaplan-Meier analysis were performed to characterize AS criteria and identify variables that predict disease reclassification. Finally, decision curve analysis (DCA) was performed to evaluate the net benefit of using PV in addition to standard variables to predict disease reclassification.ResultsPCa was diagnosed by systematic transrectal ultrasound-guided prostate biopsy (TRUS-Bx). The mean (range) follow-up was 32.7 (12-126) months. Disease reclassification occurred in 46 patients (40%). On univariate statistical analysis prostate specific antigen (PSA) (p = 0.05), prostate volume (PV) (p = 0.022), PSA density (PSAD) (p < 0.001) and number of positive cores (p = 0.021) were significant factors for disease reclassification. On the multivariate analysis, PSAD (p < 0.001) and PV (p = 0.003) were the only statistically significant independent variables to predict disease reclassification. A PSAD cut-off of 0.16 ng/ml² and a PV cut-off of 44 ml gave a maximal area under the curve, 0.69 and 0.63, respectively. Kaplan-Meier analysis showed that the median survival free from disease reclassification during AS was almost doubled in patients with PSAD < 0.16 ng/ml2 or PV > 44 ml. DCA showed a positive net benefit and clinical usefulness of the model, including PV, to predict disease reclassification between threshold probabilities of 20-50%.ConclusionsPV and PSAD significantly predicted failure from AS in our patients. Patients with a baseline PV of fewer than 44 ml would be more likely to have disease reclassification and unsuitable for acceptable AS protocols. Therefore, we believe that PV may help to select PCa patients for AS, especially in populations where the use of mpMRI is limited.

Translation of Prognostic and Pharmacodynamic Biomarkers from Trial to Non-trial Patients with Metastatic Castration-resistant Prostate Cancer Treated with Docetaxel

AimsWe conducted a pooled analysis of four randomised controlled trials and a non-trial retrospective dataset to study the changes in serum prostate-specific antigen (PSA) concentrations during treatment and its impact on survival in men treated with docetaxel for metastatic castration-resistant prostate cancer. We also compared the outcomes and pre-treatment prognostic factors between trial and non-trial patients. Materials and methodsData were obtained from four randomised controlled trials and a non-trial cohort from a tertiary cancer centre. The PSA kinetics covariates chosen were absolute value (PSAT), best percentage change (BPCH) and tumour growth rate (K). The association between the covariates collected and overall survival was assessed within a Cox proportional hazards model. How well a covariate captured the difference between trial and non-trial patients was assessed by reporting on models with or without trial status as a covariate. ResultsWe reviewed individual datasets of 2282 patients. The median overall survival for trial patients was 20.4 (95% confidence interval 19.6–22.2) months and for the non-trial cohort was 12.4 (10.7–14.7) months (P < 0.001). Of the pre-treatment factors, we found that only lactate dehydrogenase fully captured the difference in prognosis between the trial and non-trial cohorts. All PSA kinetic metrics appeared to be prognostic in both the trial and non-trial patients. However, the effect size was reduced in non-trial versus trial patients (interaction P < 0.001). Of the time-dependent covariates, we found that BPCH best captured the difference between trial and non-trial patient prognosis. ConclusionsThe analysis presented here highlights how data from open-source trial databases can be combined with emerging clinical practice databases to assess differences between trial versus non-trial patients for particular treatments. These results highlight the importance of developing prognostic models using both pre-treatment and time-dependent biomarkers of new treatments.

Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors.

Simple SummaryProstate cancer is a major medical issue in men worldwide. In 2018, prostate cancer was the most frequently diagnosed cancer among men in developed countries. MicroRNAs seem to be important regulators of prostate cancer, but better understanding of their role in this disease is still needed to develop novel diagnostic tools and treatments. In this study, we aim to achieve insight on the microRNA profile of prostatic tissue environment in men with prostate cancer and to correlate this microRNA expression profile with risk factors of prostate cancer. We also examined the effects of cholesterol-lowering atorvastatin on the prostatic tissue microRNA profile. Our results provide new evidence from the effects of prostate cancer-related factors on the expression of prostate tissue microRNAs. Notably, this can reveal new pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities.MicroRNAs are important in prostate cancer development, progression and metastasis. The aim of this study was to test microRNA expression profile in prostate tissue obtained from prostate cancer patients for associations with various prostate cancer related factors and to pinpoint the predicted target pathways for these microRNAs. Prostate tissue samples were obtained at prostatectomy from patients participating in a trial evaluating impact of pre-operative atorvastatin on serum prostate specific antigen (PSA) and Ki-67 expression in prostate tissue. Prostate tissue microRNA expression profiles were analyzed using OpenArray® MicroRNA Panel. Pathway enrichment analyses were conducted for predicted target genes of microRNAs that correlated significantly with studied factors. Eight microRNAs correlated significantly with studied factors of patients after Bonferroni multiple testing correction. MiR-485-3p correlated with serum HDL-cholesterol levels. In atorvastatin-treated subjects, miR-34c-5p correlated with a change in serum PSA and miR-138-3p with a change in total cholesterol. In the placebo arm, both miR-576-3p and miR-550-3p correlated with HDL-cholesterol and miR-627 with PSA. In pathway analysis, these eight microRNAs related significantly to several pathways relevant to prostate cancer. This study brings new evidence from the expression of prostate tissue microRNAs and related pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities.

The Calculus of Serum PSA.

To review the mathematics of kinetic changes in serum prostate-specific antigen (PSA) and to use a compartmental model to derive a new kinetic measure, alpha. The calculus of kinetic measures of PSA changes with time is presented, and a compartmental model is then used to derive alpha of serum PSA. Alpha is then tested for prognostic importance in 119 men who underwent prostatectomy. The percentage of tumor in the prostate is closely related to alpha and to tumor length in diagnostic needle biopsies, but not to tumor grade. The presence of adverse pathology in the prostatectomy specimens (positive margins or T3 stage) is significantly associated with alpha, but not to tumor length or grade. The derived kinetic parameter, alpha, shows promise as a preoperative prognostic parameter, and may help sort patients into those with low vs high probability for adverse pathology features in the prostatectomy specimens.

Lu177‐PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution

Lutetium-177-PSMA (LuPSMA) is a targeted systemic radioligand treatment for metastatic castration-resistant prostate cancer (mCRPC). LuPSMA is considered as an experimental treatment not yet used in routine practice. Here, we report our experience following the introduction of LuPSMA therapy at our institution. Referred mCRPC patients were assessed for treatment suitability including Gallium-68-PSMA PET/CT and blood tests. Suitable patients underwent up to four cycles of LuPSMA treatment. Response to treatment was assessed by changes in serum prostate-specific antigen (PSA) levels. Toxicity was assessed by recording of adverse events. In an 18month period, 50 patients underwent 132 cycles of LuPSMA therapy. Patients underwent a median of three cycles each (range: 1-4) and the mean administered amount of activity per cycle was 5.9 GBq (range: 3.5-8.2 GBq). PSA decline could be calculated for 49 patients, with a best PSA decline of≥50% observed in 22 patients (44.9%). Adverse events were reported across 45 of 132 LuPSMA cycles. Most adverse events were grade I (42/45) and the remaining three events were grade II. Initial experience at our site supports the use of LuPSMA as an emerging safe and effective treatment for mCRPC. Since introducing LuPSMA therapy at our institution, 44.9% of patients have experienced a decline in PSA level≥50% with low or minimal toxicity. This is an important finding as these patients had previously exhausted all available treatment options. Overall, we have found patients and their primary care doctors have eagerly accepted LuPSMA as another line of defence against mCRPC.

Oral administration of cernitin pollen extract (Cernilton® ) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study.

To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

IMPLICATION OF PROSTATE SPECIFIC ANTIGEN IN BENIGN PROSTATIC HYPERPLASIA

Background: Prostate-specific antigen (PSA) is the prostatic tumour marker of choice. Because PSA is not prostate cancer specific and prostate cancer develops in man at an age when the prevalence of benign prostatic hyperplasia is high, several parameters have been developed and investigated to enhance the sensitivity and specificity of the PSA test. The parameters included are PSA density (serum PSA concentration divided by the size of the prostate gland), PSA velocity (change in serum PSA over time), age specific reference ranges for serum PSA, percent free PSA, Digital rectal examination. Aim and Objectives: The aim of this study is to find out the implication of prostate specific antigen in benign prostatic hyperplasia. Materials and Methods: In this research, a correlative study of total serum PSA with digital rectal examination, prostatic volume, Transabdominal Ultrasonography, urine analysis with culture and sensitivity and histopathological examination of the patients with prostatic hyperplasia was done in 100 patients. Here our exclusion criterion was the patients with carcinoma of prostate. PSA was estimated in fasting blood sample and was collected when patient is without Foleys catheter or with catheter (24 hours after catheterization). It was estimated by Ciba Corning Automated Chemiluminescence System (ACS) using both monoclonal and polyclonal antiPSA antibody titers. Results and conclusion: Age specific rise in Serum prostate specific antigen level was found. The prostatic volume was highly significant in correlation with Serum prostate specific antigen. Digital Rectal Examination when compared with other parameters was found not to be significant in predicting the prostatic disease. The Total Serum PSA level done in all the cases does not show significance and none of the patients had malignancy even with Serum PSA> 4ng/ml. When prostate specific antigen density was calculated and compared with biopsy report positively, it was significant and was helpful in predicting the prostatic diseases and prognosis. With this we conclude that clinical correlation with Digital Rectal Examination and Transabdominal Ultrasound is very much helpful in predicting malignancy than totally relying on Serum PSA. We found that PSA is neither organ specific chemical nor disease specific.

Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A Randomized Controlled Clinical Trial

To evaluate asymptomatic men with elevated serum prostate-specific antigen (PSA) to determine whether a 6-week course of fluoroquinolone antibiotics lowers serum PSA and affects recommendations for prostate biopsy. A randomized, single-center prospective trial of 150 men with an initial elevated PSA was conducted. Patients were randomized to 6 weeks of ciprofloxacin or observation. Those patients with persistently elevated PSA were recommended to proceed with transrectal ultrasound-guided 12-core biopsy. Those with reduced PSA were offered transrectal ultrasound-guided biopsy but could opt to continue serial digital rectal examination/PSA. Patients were followed an average of 4.6 years to assess trends in PSA and biopsy results. Of 136 men who completed the trial, 63 were in the treatment and 73 were in the observation group. The average PSA change from baseline was borderline statistically significant with a change of -0.68 ng/mL in the treatment arm and 0.01 ng/mL in the observation arm (P = .052). Of those who underwent biopsy, prostate cancer was diagnosed in the first biopsy in 24 (63%) of the treatment vs 27 (52%) of the observation group (P = .60) over follow-up. In a cohort of asymptomatic men with elevated PSA, there was only a borderline statistically significant change in serum PSA between patients randomized to a 6-week course of fluoroquinolones vs observation, and there was no difference in positive prostate biopsy results. Our clinical recommendation is one should not treat patients with elevated serum PSA with antibiotics in the absence of clinical symptoms of prostatitis.

The use of multiphase nonlinear mixed models to define and quantify long-term changes in serum prostate-specific antigen: data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

PurposeTo test the hypothesis that the pattern of prostate-specific antigen (PSA) change in men diagnosed with high-risk prostate cancer (PrCA) differs from the pattern evident in men diagnosed with low-risk PrCA or those with no evidence of PrCA. MethodsA retrospective cohort study from which PSA measures were taken before PrCA diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Data were fitted using a nonlinear regression model to estimate the adjusted absolute and relative (%) change of PSA. ResultsData on 20,888 men with an average age of 61.61 years were included in the analysis. Of these, the 324 (1.55%) diagnosed with high-risk PrCA had a steeper and earlier transition into an exponential pattern of PSA change than the 1368 men diagnosed with low-risk cancer. At 1 year before diagnosis and/or exit, the average absolute PSA rates were 0.05 ng/mL/year (0.05–0.05), 0.59 (0.52–0.66), and 2.60 (2.11–3.09) for men with no evidence of PrCA, men with low-risk PrCA and those with high-risk PrCA, respectively. ConclusionsThe pattern of PSA change with time was significantly different for men who develop high-risk PrCA from those diagnosed with low-risk PrCA. Further research is required to validate this method and its utilization in PrCA screening.

The role of diffusion-weighted MRI: In assessment of response to radiotherapy for prostate cancer

ObjectiveThe objective of our study was to investigate the changes of apparent diffusion coefficient (ADC) values in prostate cancers before and after radiotherapy at 1.5T using a phased-array coil. Materials and methodsTwenty-five patients with biopsy-proven prostate cancer who received radiotherapy underwent diffusion-weighted imaging (DWI) at 1.5T and were included in the study. Biopsies in all patients were performed before the initial MRI examination (range, 15–30days before MRI; mean, 21.1days). All 25 patients underwent DWI (b values=0 and 1000s/mm2) before and 1–3months after the completion of radiotherapy. The changes in ADC values were measured for cancers and benign tissues before and after therapy. Additionally, the changes in serum prostate-specific antigen (PSA) levels were evaluated before and after therapy. ResultsThe mean ADC value after therapy (1.418×10−3mm2/s) was increased compared with the mean ADC value before therapy (0.756×10−3mm2/s) (p<0.001) in cancer prostate. After radiotherapy, the mean ADC values of benign peripheral zones and of benign transition zones were statistically significantly decreased compared with those before radiotherapy (p<0.05). Before treatment, a significant difference of ADC values between the tumors and benign tissues was found (p<0.001), whereas there was no significant difference of ADC values between them after treatment (p>0.5). The median PSA level after therapy (1.39ng/mL) was decreased compared with the median PSA level before therapy (27.20ng/mL). ConclusionWith the use of a 1.5-T MR scanner, our preliminary results suggest that ADC values may be useful as a non-invasive imaging biomarker for monitoring therapeutic response of prostate cancer to radiotherapy.

Prostate specific antigen. Current clinical application and future prospects.

Prostate-specific antigen (PSA) is a glycoprotein produced by the prostate gland and its production can be enhanced in benign and malignant diseases. The introduction of PSA testing has greatly increased the detection of prostate cancer. However there is continuing controversy and confusion over the most appropriate application of the PSA test. PubMed and Web of Science databases were used to search original and review articles on the historical aspects, clinical utilization and possible future directions in PSA. After its discovery, PSA was quickly established as an exquisitely sensitive tumor marker for prostate cancer detection, assessment of treatment responses and follow-up among patients with prostate cancer. Nevertheless, controversy exists about the proper threshold for recommending prostate biopsy. If this limit is lowered to improve the sensitivity even more, patients with low-risk prostate cancer would be subsequently detected. Post-treatment PSA levels can certainly provide valuable information about the effectiveness of the therapy given. Recently introduced ultrasensitive PSA detection techniques are offering new insight into the changes in serum PSA at very low concentrations. This has resulted in identification of valuable postoperative prognostic variables together with the possibility of earlier cancer relapse detection. The development of assays that may show superior sensitivity and specificity in prostate cancer diagnosis is focused on proteins possibly complexed with PSA and other potential markers detectable both in serum and urine. The goal of newly discovered prostate cancer biomarkers is greater cancer specificity in order to reduce the overdiagnosis, overtreatment and financial cost.

Effect of Alpha Linolenic Acid Supplementation on Serum Prostate Specific Antigen (PSA): Results from the Alpha Omega Trial

BackgroundAlpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.MethodsThe Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL).FindingsMean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).InterpretationAn additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.Trial registration informationClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

Changes in S-PSA after transurethral resection of prostate and its correlation to postoperative outcome

Although different factors may affect prostate-specific antigen (PSA) reduction after transurethral resection of prostate, an approximate 70 % decrease from baseline is expected. We hereby undertook a prospective study to analyze changes in serum PSA (S-PSA) after transurethral resection of the prostate (TURP) and its correlation with the residual prostatic weight and clinical symptom score improvement. Seventy patients who underwent TURP for bladder outlet obstruction were included in the study. Patient's evaluation included history, International Prostate Symptom Score (IPSS), S-PSA, Qmax, post-void residual urine and prostate size. On follow-up, trans-rectal ultrasonography, S-PSA and IPSS score were calculated. Patients were analyzed in three groups based on the amount of tissue resected: less than 40, 40-60 and more than 60 % tissue resected. Preoperative prostate size, IPSS, Qmax and S-PSA were 62.56 ml, 23.84, 11.68 ml/sec and 3.3 ng/ml. There was a significant decrease in the IPSS score, prostate size and S-PSA levels after TURP in all the three groups. There was a significant positive correlation of the amount of tissue resected with change in S-PSA levels, change in IPSS score and postoperative IPSS score. Reduction in IPSS score significantly correlated with patient's satisfaction. The amount of tissue resected in TURP has a direct bearing on the S-PSA levels, change in symptom score and residual prostate volume. It is the percentage change in IPSS score and not the absolute value of IPSS, which has a direct bearing with the patient satisfaction and with the amount of tissue resected. Percentage fall in S-PSA by 70 % was found to be predictor of more than 60 % resection.

Impact of Treatment With Statins on Prostate-Specific Antigen and Prostate Volume in Patients With Benign Prostatic Hyperplasia

PurposeWe investigated the impact on prostate-specific antigen (PSA) and prostate volume (PV) of statin medication for 1 year in patients with benign prostatic hyperplasia (BPH).Materials and MethodsWe retrospectively investigated 791 patients in whom BPH was diagnosed. For analysis, the patients were divided into four groups according to their medications: group A, α-blocker; group B, α-blocker+statin; group C, α-blocker+dutasteride; group D, α-blockers+statin+dutasteride. To investigate changes in serum PSA, PV, and total cholesterol, we analyzed the data at the time of initial treatment and after 1 year of medication.ResultsAfter 1 year, group A showed a 1.3% increase in PSA and a 1.0% increase in PV. Group B showed a 4.3% decrease in PSA and a 1.8% decrease in PV. The difference in PV reduction between groups A and B was statistically significant (p<0.001). Group C showed a 49.1% reduction in PSA and a 22.9% reduction in PV. Group D showed a 51.6% reduction in PSA and a 24.5% reduction in PV. The difference in PV reduction between groups C and D was not statistically significant (p=0.762). By use of a multivariate logistic regression model, we found that the probability of PV reduction after 1 year was more than 14.8 times in statin users than in statin nonusers (95% confidence interval, 5.8% to 37.6%; p<0.001).ConclusionsStatin administration reduced PSA and PV in BPH patients. This finding may imply the improvement of lower urinary tract symptoms and prevention of cardiovascular disease and chemoprevention of prostate cancer with statin treatment.

Abstract B68: Antioxidant activity of green tea: A phase II clinical trial in men with prostate cancer

Abstract Background: Green tea (GT) contains green tea polyphenols (GTPs) which have been shown to play a role in the regulation of cell proliferation and apoptosis in prostate cancer cells in vitro and in animal models using human prostate cancer cell xenografts. GTPs are also potent scavengers of reactive oxygen species (ROS) which play a role in tumorigenesis. While there is extensive epidemiological and basic science evidence for these effects of GTPs, data from human intervention studies is much more limited. Objective: We conducted a phase II intervention study to evaluate the anticarcinogenic and antioxidant effects of green tea in prostate cancer by administering green tea in men prior to prostatectomy. Design: 79 men, diagnosed with prostate cancer and scheduled for prostatectomy, were randomized to either 6 cups of brewed green tea (GT group, N=34) or water (control group, N=33) daily for 3-8 weeks prior to surgery. 67 men completed the intervention. Blood and urine samples were collected before and after the intervention, and a section of prostate tissue was obtained following the pathology evaluation. Serum prostate specific antigen (PSA) concentration was determined by ELISA assay and prostate tissue PSA protein concentration was measured by Western blot. The prostate concentration of GTPs and their metabolites was measured using high-performance liquid chromatography (HPLC) with CoulArray electrochemical detection. The concentration of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker for oxidative DNA damage, was measured in urine by HPLC. In addition, gene expression of the antioxidant enzymes superoxide dismutase (SOD) and catalase were determined in normal and tumor prostate tissue using real-time quantitative PCR. Results: Statistical analysis within each treatment arm showed that the serum PSA concentration significantly decreased in the GT group (final vs. baseline blood) (P&amp;lt;0.01), while no change was observed in the control group. The comparison of percent change in serum PSA between GT and control group showed a decreasing trend (p=0.085). Prostate tissue PSA protein expression was lower in men consuming GT compared to water control (p=0.06). The major bioactive component of GTPs, epigallocatechin gallate (EGCG) and its methyl metabolite 4″-O-methyl EGCG were found in prostate tissue in similar amounts, along with a small amount of epicatechin gallate. As compared to the pre-intervention level there was a significant decrease in urinary 8-OHdG concentration after GT intervention (83 vs. 50 nmol/g creatinine), while there was no change in the control group (54 vs. 55 nmol/g creatinine). Gene expression of SOD (p=0.087) and catalase (p=0.15) in the prostate tumor tissue normalized to normal prostate tissue in each individual showed a decreasing trend in men consuming GT as compared to the water control. Conclusion: The consumption of 6 cups of GT provided antioxidant protection, which may contribute to an inhibitory effect on prostate tumor growth in humans. Large-scale human intervention studies are needed to confirm these findings. Citation Format: Piwen Wang, William Aronson, Narine Abgaryan, Catherine L. Carpenter, Jaydutt V. Vadgama, David Heber, Susanne M. Henning. Antioxidant activity of green tea: A phase II clinical trial in men with prostate cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B68.

Changes in Serum PSA During Normal Menstrual Cycle

Prostate specific antigen (PSA) has long been used as a biological marker for prostatic cancer. Recent studies have demonstrated that PSA synthesis can be induced by steroid hormones in several tissues of women. Menstrual cycle is regulated by the cyclic variation of estradiol and progesterone. This study was undertaken in order to study the correlation of serum PSA to both these corpus luteal hormones. 110 serum samples and 10 saliva samples were collected from healthy women aged 18-45years of age having normal menstrual cycles. Active PSA DSL-9700 ultrasensitive kit with detection limit 0.001ng/ml was used to analyze PSA. 38.2% of all serum samples and 10% of saliva samples had detectable concentrations of PSA. The serum PSA was highest during mid follicular phase (between 4th and 8th days of cycle). Variation in PSA levels seemed to follow the variations in progesterone with a lag period of 12-14days, but did not appear to bear any relationship with the estradiol levels.

163 RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL OF POLYPHENON E IN PROSTATE CANCER PATIENTS BEFORE RADICAL PROSTATECTOMY: EVALUATION OF POTENTIAL CHEMOPREVENTIVE ACTIVITIES

Compelling preclinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double-blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate-specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant. The study’s findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease. Cancer Prev Res; 5(2); 290–8. � 2011 AACR.

Randomized, Double-Blind, Placebo-Controlled Trial of Polyphenon E in Prostate Cancer Patients before Prostatectomy: Evaluation of Potential Chemopreventive Activities

Compelling preclinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double-blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate-specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant. The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease.