Loeb S. Germline Sequence Variants and Prostate-Specific Antigen Interpretation. Clinical Chemistry 2012;57(5):662-3. Germline Sequence Variants and Prostate-Specific Antigen Interpretation
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Loeb S. Germline Sequence Variants and Prostate-Specific Antigen Interpretation. Clinical Chemistry 2012;57(5):662-3. Germline Sequence Variants and Prostate-Specific Antigen Interpretation
Iwounder does it get ya off too....
SOund.. Hmmm.. Ive tried everything else. What the heck...
SOund.. Hmmm.. Ive tried everything else. What the heck...
Mostaghel EA, Solomon KR, Pelton K, Freeman MR, Montgomery RB. Impact of circulating cholesterol levels on growth and intratumoral androgen concentration of prostate tumors. PLoS One 2012;7(1):e30062. PLoS ONE: Impact of Circulating Cholesterol Levels on Growth and Intratumoral Androgen Concentration of Prostate Tumors
Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol.
Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025)
Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis.
Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR.
Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol.
Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025)
Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis.
Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR.
Editorial. PSA Screening And Low Risk Prostate Cancer, What's Going On? Are We Shooting The Messenger?
Martinez-Salamanca JI. Editorial. PSA screening and low risk prostate cancer, what's going on? are we shooting the messenger? Arch Esp Urol 2012;65(2):209-14. ART
Martinez-Salamanca JI. Editorial. PSA screening and low risk prostate cancer, what's going on? are we shooting the messenger? Arch Esp Urol 2012;65(2):209-14. ART
Engehausen DG, Engelhard K, Schwab SA, et al. Magnetic resonance image-guided biopsies with a high detection rate of prostate cancer. Scientific World Journal 2012:975971. Magnetic Resonance Image-Guided Biopsies with a High Detection Rate of Prostate Cancer
AIM: To explore the potential of transrectal magnetic resonance image- (MRI-) guided biopsies of the prostate in a patient cohort with prior negative ultrasound guided biopsies.
PATIENTS AND METHODS: Ninety-six men with suspected prostate cancer underwent MRI-guided prostate biopsies under real-time imaging control in supine position.
RESULTS: Adenocarcinoma of the prostate was detected in 39 of 96 patients. For individual core biopsies, MRI yielded a sensitivity of 93.0% and a specificity of 94.4%. When stratifying patients according to the free-to-total prostate-specific antigen (PSA) ratio, the prostate cancer discovery rate was significantly higher in the group with ratios less than 0.15 (57.1%).
CONCLUSION: MRI-guided biopsy of the prostate is a diagnostic option for patients with suspected prostate cancer and a history of repeatedly negative transrectal ultrasound-guided biopsies. Combined with the free-to-total PSA ratio, it is a highly effective method for detecting prostate cancer.
AIM: To explore the potential of transrectal magnetic resonance image- (MRI-) guided biopsies of the prostate in a patient cohort with prior negative ultrasound guided biopsies.
PATIENTS AND METHODS: Ninety-six men with suspected prostate cancer underwent MRI-guided prostate biopsies under real-time imaging control in supine position.
RESULTS: Adenocarcinoma of the prostate was detected in 39 of 96 patients. For individual core biopsies, MRI yielded a sensitivity of 93.0% and a specificity of 94.4%. When stratifying patients according to the free-to-total prostate-specific antigen (PSA) ratio, the prostate cancer discovery rate was significantly higher in the group with ratios less than 0.15 (57.1%).
CONCLUSION: MRI-guided biopsy of the prostate is a diagnostic option for patients with suspected prostate cancer and a history of repeatedly negative transrectal ultrasound-guided biopsies. Combined with the free-to-total PSA ratio, it is a highly effective method for detecting prostate cancer.
Basch E, Oliver TK, Vickers A, et al. Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion. Journal of Clinical Oncology. Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion
Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer.
Clinical Context Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection.
Recent Data Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic.
Results In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.
Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer.
Clinical Context Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection.
Recent Data Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic.
Results In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.
A single nucleotide polymorphism-based genetic score is a prostate cancer (PCa) risk factor. This study suggests that those men with intermediate clinical risk following an initial negative prostate biopsy for PCa may benefit most from this form of testing.
Kader AK, Jielin S, Brian HR, et al. Potential Impact of Adding Genetic Markers to Clinical Parameters in Predicting Prostate Biopsy Outcomes in Men Following an Initial Negative Biopsy: Findings from the REDUCE Trial. European Urology. Potential Impact of Adding Genetic Markers to Clinical Parameters in Predicting Prostate Biopsy Outcomes in Men Following an Initial Negative Biopsy: Findings from the REDUCE Trial - European Urology
Background - Several germline single nucleotide polymorphisms (SNPs) have been consistently associated with prostate cancer (PCa) risk.
Objective - To determine whether there is an improvement in PCa risk prediction by adding these SNPs to existing predictors of PCa.
Design, setting, and participants - Subjects included men in the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial in whom germline DNA was available. All men had an initial negative prostate biopsy and underwent study-mandated biopsies at 2 yr and 4 yr. Predictive performance of baseline clinical parameters and/or a genetic score based on 33 established PCa risk-associated SNPs was evaluated.
Outcome measurements and statistical analysis - Area under the receiver operating characteristic curves (AUC) were used to compare different models with different predictors. Net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess changes in risk prediction by adding genetic markers.
Results and limitations - Among 1654 men, genetic score was a significant predictor of positive biopsy, even after adjusting for known clinical variables and family history (p = 3.41 × 10?8). The AUC for the genetic score exceeded that of any other PCa predictor at 0.59. Adding the genetic score to the best clinical model improved the AUC from 0.62 to 0.66 (p < 0.001), reclassified PCa risk in 33% of men (NRI: 0.10; p = 0.002), resulted in higher net benefit from DCA, and decreased the number of biopsies needed to detect the same number of PCa instances. The benefit of adding the genetic score was greatest among men at intermediate risk (25th percentile to 75th percentile). Similar results were found for high-grade (Gleason score ?7) PCa. A major limitation of this study was its focus on white patients only.
Conclusions - Adding genetic markers to current clinical parameters may improve PCa risk prediction. The improvement is modest but may be helpful for better determining the need for repeat prostate biopsy. The clinical impact of these results requires further study.
Kader AK, Jielin S, Brian HR, et al. Potential Impact of Adding Genetic Markers to Clinical Parameters in Predicting Prostate Biopsy Outcomes in Men Following an Initial Negative Biopsy: Findings from the REDUCE Trial. European Urology. Potential Impact of Adding Genetic Markers to Clinical Parameters in Predicting Prostate Biopsy Outcomes in Men Following an Initial Negative Biopsy: Findings from the REDUCE Trial - European Urology
Background - Several germline single nucleotide polymorphisms (SNPs) have been consistently associated with prostate cancer (PCa) risk.
Objective - To determine whether there is an improvement in PCa risk prediction by adding these SNPs to existing predictors of PCa.
Design, setting, and participants - Subjects included men in the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial in whom germline DNA was available. All men had an initial negative prostate biopsy and underwent study-mandated biopsies at 2 yr and 4 yr. Predictive performance of baseline clinical parameters and/or a genetic score based on 33 established PCa risk-associated SNPs was evaluated.
Outcome measurements and statistical analysis - Area under the receiver operating characteristic curves (AUC) were used to compare different models with different predictors. Net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess changes in risk prediction by adding genetic markers.
Results and limitations - Among 1654 men, genetic score was a significant predictor of positive biopsy, even after adjusting for known clinical variables and family history (p = 3.41 × 10?8). The AUC for the genetic score exceeded that of any other PCa predictor at 0.59. Adding the genetic score to the best clinical model improved the AUC from 0.62 to 0.66 (p < 0.001), reclassified PCa risk in 33% of men (NRI: 0.10; p = 0.002), resulted in higher net benefit from DCA, and decreased the number of biopsies needed to detect the same number of PCa instances. The benefit of adding the genetic score was greatest among men at intermediate risk (25th percentile to 75th percentile). Similar results were found for high-grade (Gleason score ?7) PCa. A major limitation of this study was its focus on white patients only.
Conclusions - Adding genetic markers to current clinical parameters may improve PCa risk prediction. The improvement is modest but may be helpful for better determining the need for repeat prostate biopsy. The clinical impact of these results requires further study.
Wilt TJ, Brawer MK, Jones KM, et al. Radical Prostatectomy versus Observation for Localized Prostate Cancer. New England Journal of Medicine 2012;367(3):203-13. MMS: Error
BACKGROUND - The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.
METHODS - From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.
RESULTS - During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.
CONCLUSIONS - Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points.
BACKGROUND - The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.
METHODS - From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.
RESULTS - During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.
CONCLUSIONS - Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points.
Scosyrev E, Wu G, Mohile S, Messing EM. Prostate-specific antigen screening for prostate cancer and the risk of overt metastatic disease at presentation. Cancer. Prostate-specific antigen screening for prostate cancer and the risk of overt metastatic disease at presentation - Scosyrev - 2012 - Cancer - Wiley Online Library
BACKGROUND: The objective of this study was to estimate the total number of patients who would be expected to present with metastatic (M1) prostate cancer (PC) in the modern US population in a given year if the age-specific and race-specific annual incidence rates of M1 PC were the same as the rates in the era before prostate-specific antigen (PSA) testing.
METHODS: The authors computed the total number of men who presented with M1 PC in the Surveillance, Epidemiology, and End Results (SEER) 9 registries area in the year 2008 (the most recent SEER year) and estimated the number of cases that would be expected to occur in this area in the year 2008 in the absence of PSA testing. The expected number was computed by multiplying each age-race–specific average annual incidence rate from the pre-PSA era (1983-1985) by the number of men in the corresponding age-race category in the year 2008 and adding the products.
RESULTS: In the year 2008, the observed and expected numbers of men presenting with M1 PC in the SEER 9 registries area were 739 and 2277, respectively, with an expected-to-observed ratio of 3.1 (95% confidence interval, 3.0-3.2). If this ratio was applied to the total US population in the year 2008, then the total number of men presenting with M1 PC in that year would be equal to approximately 25,000 instead of the approximately 8000 actually observed.
CONCLUSIONS: If the pre-PSA era rates were present in the modern US population, then the total number of men presenting with M1 PC would be approximately 3 times greater than the number actually observed.
BACKGROUND: The objective of this study was to estimate the total number of patients who would be expected to present with metastatic (M1) prostate cancer (PC) in the modern US population in a given year if the age-specific and race-specific annual incidence rates of M1 PC were the same as the rates in the era before prostate-specific antigen (PSA) testing.
METHODS: The authors computed the total number of men who presented with M1 PC in the Surveillance, Epidemiology, and End Results (SEER) 9 registries area in the year 2008 (the most recent SEER year) and estimated the number of cases that would be expected to occur in this area in the year 2008 in the absence of PSA testing. The expected number was computed by multiplying each age-race–specific average annual incidence rate from the pre-PSA era (1983-1985) by the number of men in the corresponding age-race category in the year 2008 and adding the products.
RESULTS: In the year 2008, the observed and expected numbers of men presenting with M1 PC in the SEER 9 registries area were 739 and 2277, respectively, with an expected-to-observed ratio of 3.1 (95% confidence interval, 3.0-3.2). If this ratio was applied to the total US population in the year 2008, then the total number of men presenting with M1 PC in that year would be equal to approximately 25,000 instead of the approximately 8000 actually observed.
CONCLUSIONS: If the pre-PSA era rates were present in the modern US population, then the total number of men presenting with M1 PC would be approximately 3 times greater than the number actually observed.
DEFINITIONS FOR US CHALLENGED..
1. What is metastatic cancer?
Metastatic cancer is cancer that has spread from the place where it first started to another place in the body. A tumor formed by metastatic cancer cells is called a metastatic tumor or a metastasis. The process by which cancer cells spread to other parts of the body is also called metastasis.
http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic
1. What is metastatic cancer?
Metastatic cancer is cancer that has spread from the place where it first started to another place in the body. A tumor formed by metastatic cancer cells is called a metastatic tumor or a metastasis. The process by which cancer cells spread to other parts of the body is also called metastasis.
http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic
Hurst R, Hooper L, Norat T, et al. Selenium and prostate cancer: systematic review and meta-analysis. Am J Clin Nutr 2012;96(1):111-22. Selenium and prostate cancer: systematic review and meta-analysis
BACKGROUND: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent.
OBJECTIVE: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk.
DESIGN: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk.
RESULTS: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 mug/g.
CONCLUSION: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.
BACKGROUND: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent.
OBJECTIVE: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk.
DESIGN: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk.
RESULTS: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 mug/g.
CONCLUSION: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.
Doc, Does that say a 95% Risk Reduction associated with this level of selenium?
Projecting Prostate Cancer Mortality In The PCPT And REDUCE Chemoprevention Trials [Finasteride & Dutasteride]
Pinsky PF, Black A, Grubb R, et al. Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials. Cancer. Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials - Pinsky - 2012 - Cancer - Wiley Online Library
BACKGROUND.: Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff.
METHODS.: The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume.
RESULTS.: For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08).
CONCLUSIONS.: Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2012. (c) 2012 American Cancer Society.
Pinsky PF, Black A, Grubb R, et al. Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials. Cancer. Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials - Pinsky - 2012 - Cancer - Wiley Online Library
BACKGROUND.: Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff.
METHODS.: The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume.
RESULTS.: For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08).
CONCLUSIONS.: Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2012. (c) 2012 American Cancer Society.
Cheng L, Montironi R, Bostwick DG, Lopez-Beltran A, Berney DM. Staging of prostate cancer. Histopathology 2012;60(1):87-117. Staging of prostate cancer - Cheng - 2011 - Histopathology - Wiley Online Library
Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.
Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.
Histopathology - Prostate Cancer Special
Histopathology - Volume 60, Issue 1 - January 2012 - Wiley Online Library
Histopathology - Volume 60, Issue 1 - January 2012 - Wiley Online Library
Prostate Cancer: Six Things Men Should Know About Tomatoes, Fish Oil, Vitamin Supplements, Testosterone, PSA Tests
Prostate cancer: Six things men should know about tomatoes, fish oil, vitamin supplements, testosterone, PSA tests
Prostate cancer: Six things men should know about tomatoes, fish oil, vitamin supplements, testosterone, PSA tests
Thanks for the url. I think it was myth #3 that elevated testosterone does not lead to prostate cancer. But that's testosterone in the blood. Dr Gat in Israel has shown that with age the veins draining the prostate become incompetent leading to chronic congestion of the prostate. This causes very high levels of testosterone WITHIN the prostate. This leads to cancer.
koneall
koneall
[NOTE: NO FOLLOW-UP OR INDEPENDENT INVESTIGATOR CONFIRMATION]
Gat Y, Joshua S, Gornish MG. Prostate cancer: a newly discovered route for testosterone to reach the prostate : Treatment by super-selective intraprostatic androgen deprivation. Andrologia 2009;41(5):305-15. Prostate cancer: a newly discovered route for testosterone to reach the prostate - Gat - 2009 - Andrologia - Wiley Online Library
The prostate, an androgen-regulated exocrine gland, is an integral part of the male reproductive system which has an essential function in sperm survival and motility in its long hostile route to meet and fertilise the egg in the Fallopian tube. Testosterone is known to be the key, obligatory regulator of the prostate that promotes the development and progression of prostate cancer (PCa). Yet, the pathophysiological mechanism of PCa remains unclear and its causal relation to serum testosterone has not been established. Here, we report on the discovery of a previously unrecognized route of flow of free testosterone (FT), at a concentration of 130 times the physiological levels, reaching the prostate via the testicular and prostate venous drainage systems, bypassing the systemic circulation. This condition results from the malfunction of the vertically oriented testicular venous drainage system in humans, a phenomenon with a prevalence that increases rapidly with age, which causes deviation of the testicular venous flow from its normal route. Early results of an interventional radiological procedure, super-selective intraprostatic androgen deprivation therapy are discussed. This treatment has resulted in decrease in prostate volume, and serum PSA, with disappearance of cancerous cells on repeat biopsies in five of six patients. Some of the unresolved biological enigmatic questions associated with PCa are discussed. We conclude that pathological flow of FT from the testes directly to the prostate in an extremely high concentration via the testicular-prostate venous drainage systems was identified may explain the mechanism for the development of PCa. We suggest a time-window for eradication of localised, androgen-sensitive, PCa cells. We anticipate that this treatment may retard, stop or even reverse the development of the disease. A mechanism for the evolution of PCa is discussed.
For BPH, see: Gat Y, Gornish M, Heiblum M, Joshua S. Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment. Andrologia 2008;40(5):273-81. https://thinksteroids.com/community/posts/804132
more doctors have dropped the range for psa from 0- 4 to 0 - 2.5 . they also look at velocity meaning some with a base psa of .4 all of the sudden jumps to 1.1 . although well under the top of the range, the velocity of the increase raises a red flag. of course a sudden rise can be due to infection as well which needs to be ruled out.
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