Risk Of Prostate Cancer Mortality Research Articles

Cholesterol metabolism and prostate cancer-specific mortality.

12 Background: Cholesterol is needed in prostate cancer cells for cell proliferation and for androgen biosynthesis. Cholesterol-lowering statin drug use is associated with a lower risk of total and advanced prostate cancer and lower prostate cancer-specific mortality (PCSM). We hypothesized that tumor expression of cholesterol synthesis enzymes, transporters and regulators is associated with PCSM. Methods: We studied mRNA expression of 43 cholesterol metabolism genes in surgical specimens from 249 participants in the Health Professionals' Follow-up Study diagnosed with prostate cancer between 1986 and 2004. We included 81 cases of lethal prostate cancer and 168 indolent cases who survived >8 years without metastases. After multivariate dimensionality reduction for the synthesis, transport and regulator pathways using principal components analysis, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. We adjusted for age, year of diagnosis, body mass index, smoking status, family history, multivitamin use, high serum cholesterol and cholesterol-lowering drug use. Results: Reflecting the impact of the synthesis pathway and of the regulator pathway, respectively, the expression of squalene epoxidase (SQLE) and low-density lipoprotein receptor (LDLR) were significantly associated with lethal cancer in opposing directions. Compared to men with the mean level of SQLE expression, men with SQLE expression >1 standard deviation (SD) above the mean were 15.4 times more likely to have lethal cancer (95% CI: 3.31–71.53). For LDLR, expression >1 SD above the mean was associated with 96% lower odds of lethal cancer (95% CI: 0.01–0.70). Higher SQLE expression and lower LDLR expression were associated with higher Gleason grades (Fisher's test, p < 0.001 and p = 0.036, respectively) and were also predictive of PCSM independently from grade and tumor stage. Conclusions: These results suggest that the local cholesterol metabolism of the prostate tumor is tightly linked with mortality. Lethal cancers have higher activity of the second rate-controlling enzyme of cholesterol synthesis and are less dependent on cholesterol uptake.

Entacapone and Prostate Cancer Risk in Patients With Parkinson's Disease

The association between Parkinson's disease (PD) and prostate cancer, both common in elderly men, is disputable. In the STRIDE-PD study, prostate cancer developed in 9 patients (3.7%) receiving levodopa/carbidopa with entacapone, a catechol-O-methyltransferase inhibitor, versus 2 cases (0.9%) without entacapone. The current pharmacoepidemiological study aimed to determine whether entacapone increases prostate cancer incidence or mortality in PD patients and whether cumulative exposure affects these rates. We performed a retrospective cohort study using population-wide health care registers with patient-level linkage. Prostate cancer incidence and mortality were modeled by Cox's proportional hazards models. Use of entacapone with l-dopa/dopa decarboxylase inhibitor caused no increased risk of prostate cancer incidence (hazard ratio [HR]: 1.05; 95% confidence interval: 0.76-1.44) or mortality (0.93; 0.43-1.98). The HR for cumulative entacapone use of >360 days versus never-use was 0.82 (0.56-1.18) for prostate cancer incidence and 1.27 (0.60-2.72) for prostate cancer mortality.

Effect of metformin on cancer risk and treatment outcome of prostate cancer: a meta-analysis of epidemiological observational studies.

BackgroundLaboratory studies have shown the anti-tumor effect of metformin on prostate cancer. However, recent epidemiological studies have yielded inconclusive results.MethodsWe searched PubMed database from the inception to May 30 2014 for studies which assessed the effect of metformin use on cancer risk of prostate cancer, biochemical recurrence (BCR) and all-cause mortality of patients with prostate cancer. The pooled results and 95% confidence intervals (CIs) were estimated by random-effect model.ResultsTwenty-one studies were eligible according to the inclusion criteria. Based on the pooled results of available observational studies, metformin use was significantly associated with a decreased cancer risk (14 datasets, 963991 male subjects, odds ratio: 0.91, 95% CI: 0.85–0.97) and BCR (6 datasets, 2953 patients, hazard ratio: 0.81, 95% CI: 0.68–0.98) of prostate cancer. However, the association of metformin use with all-cause mortality of patients with prostate cancer was not significant (5 datasets, 9241 patients, hazard ratio: 0.86, 95% CI: 0.64–1.14).ConclusionResults suggest that metformin use appears to be associated with a significant reduction in the cancer risk and BCR of prostate cancer, but not in all-cause mortality of patients with prostate cancer.

The Use of Aspirin and the Risk of Mortality in Patients with Prostate Cancer

The association between the use of aspirin and mortality in patients with prostate cancer remains uncertain. We determine whether the use of aspirin in patients with prostate cancer is associated with a decreased risk of prostate cancer mortality and all cause mortality. Using the United Kingdom National Cancer Data Repository, Clinical Practice Research Datalink and associated databases, we identified a cohort of men with nonmetastatic prostate cancer between 1998 and 2009, followed until 2012. Cox proportional hazards models were used to estimate adjusted HRs with 95% CIs of mortality outcomes associated with post-diagnostic use of aspirin defined as a time-varying exposure. Effect modification by pre-diagnostic aspirin use was also assessed. The cohort included 11,779 men followed for 5.4 years (SD 2.9). Post-diagnostic aspirin use was associated with an increased risk of prostate cancer mortality (HR 1.46, 95% CI 1.29-1.65) and all cause mortality (HR 1.37, 95% CI 1.26-1.50). These increased risks were restricted to patients initiating aspirin after the prostate cancer diagnosis (HR 1.84, 95% CI 1.59-2.12, and HR 1.70, 95% CI 1.53-1.88, respectively), and not in patients who were already exposed to aspirin before the diagnosis (HR 0.97, 95% CI 0.81-1.16 and HR 0.98, 95% CI 0.87-1.18, respectively). The post-diagnostic use of aspirin is not associated with a decreased risk of prostate cancer outcomes. Increased risks were restricted to patients initiating these drugs after their diagnosis, suggesting a noncausal association.

Abstract PL01-03: Vitamin D deficiency and prostate cancer in men with African ancestry

Abstract African-American men are disproportionally affected by prostate cancer in that African-American men are not only at increased risk of prostate cancer compared to American men of European descent, but also are at the highest risk of aggressive prostate cancer and death from prostate cancer. As well vitamin D3 deficiency is rampant in the African-American population. There is a biological component to this deficiency because sun-induced vitamin D3 synthesis in the skin is significantly reduced in melanin-rich pigmented skin. Consequently, about two thirds of African-American men are vitamin D3 deficient compared to about 20% of men of European descent. It is important to maintain a healthy vitamin D3 status because vitamin D3 deficiency increases the risk of prostate cancer mortality. Our group has examined vitamin D3 concentrations, metabolism and mediators in prostate tissue and cells of a racially diverse group of patients to discern differences in African-American men. Citation Format: Larisa Nonn. Vitamin D deficiency and prostate cancer in men with African ancestry. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL01-03. doi:10.1158/1538-7755.DISP13-PL01-03

Post-diagnostic use of beta-blockers and the risk of death in patients with prostate cancer

BackgroundRecent observational studies have produced conflicting results with respect to beta-blocker use after prostate cancer diagnosis and mortality outcomes. ObjectiveTo determine whether post-diagnostic use of beta-blockers is associated with prostate cancer mortality and all-cause mortality. Patients and methodsA cohort of 6270 men newly-diagnosed with non-metastatic prostate cancer between 1st April 1998, and 31st December 2009, followed until 1st October 2012, was identified using large population-based electronic databases from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality outcomes associated with post-diagnostic use of beta-blockers. Secondary analyses were performed to examine the independent effects of non-selective beta-blockers, as well as cumulative duration of use. ResultsDuring a mean follow-up time of 3.8years (standard deviation: 2.7years), 1761 deaths occurred, including 715 from prostate cancer. Post-diagnostic use of beta-blockers was not associated with a decreased risk of prostate cancer mortality (HR: 0.97, 95% CI: 0.72–1.31) and all-cause mortality (HR: 0.97, 95% CI: 0.81–1.16). There was no statistically significant association for non-selective beta-blockers (prostate cancer mortality, HR: 1.05, 95% CI: 0.72–1.53 and all-cause mortality, HR: 0.94, 95% CI: 0.74–1.18), and no statistically significant trends of cumulative duration of use for both mortality outcomes. ConclusionThe use of beta blockers, including those of the non-selective type, was not associated with a decreased risk of prostate cancer and all-cause mortality.

Increasing Use of Observation among Men at Low Risk for Prostate Cancer Mortality

There are growing concerns regarding the overtreatment of localized prostate cancer. It is also relatively unknown whether there has been increased uptake of observational strategies for disease management. We assessed the temporal trend in observation of clinically localized prostate cancer, particularly in men with low risk disease, who were young and healthy enough to undergo treatment. We performed a retrospective cohort study using the SEER-Medicare database in 66,499 men with localized prostate cancer between 2004 and 2009. The main study outcome was observation within 1 year after diagnosis. We performed multivariable analysis to develop a predictive model of observation adjusting for diagnosis year, age, risk and comorbidity. Observation was performed in 12,007 men (18%) with a slight increase with time from 17% to 20%. However, there was marked increase in observation from 18% in 2004 to 29% in 2009 in men with low risk disease. Men 66 to 69 years old with low risk disease and no comorbidities had twice the odds of undergoing observation in 2009 vs 2004 (OR 2.12, 95% CI 1.73-2.59). Age, risk group, comorbidity and race were independent predictors of observation (each p <0.001), in addition to diagnosis year. We identified increasing use of observation for low risk prostate cancer between 2004 and 2009 even in men young and healthy enough for treatment. This suggests growing acceptance of surveillance in this group of patients.

Italianity is associated with lower risk of prostate cancer mortality in Switzerland.

Different prostate cancer mortality rates observed in European countries may depend on cultural background. We aimed at exploring variation in prostate cancer mortality in the language regions of Switzerland as a function of "Italianity", a proxy for adherence to an Italian lifestyle. We used data of the Swiss National Cohort, a census-based record linkage study, consisting of census (1990 and 2000) and mortality (until 2008) data. 1,163,271 Swiss and Italian nationals 40+-year old were included. Multivariate age-standardized prostate cancer mortality rates and hazard ratios (HR) from Cox proportional hazards regression analysis were performed. Italianity was defined by an individual's nationality, place of birth and principal language, resulting in a score of 0-3 points. Age-standardized prostate cancer mortality rates (per 100,000 person-years) were lowest in the Italian-speaking region of Switzerland (66.7 vs. 87.3 in the German-speaking region). Both Italian nationality and/or place of birth were significantly associated with lower mortality. There was a graded inverse association between mortality rates and increasing Italianity score. Individuals with the highest level of Italianity had a HR of 0.67 (95 % CI 0.59-0.76) compared to those with an Italianity score of zero. Results were similar when looking at language regions separately. The strong and consistent association between Italianity and prostate cancer mortality suggests protective properties of an Italian lifestyle. Further research is required in order to determine which factors specific for Italian culture are responsible for the lower prostate cancer mortality.

PTEN loss in biopsy tissue predicts poor clinical outcomes in prostate cancer.

To determine whether PTEN status in prostate biopsy represents a predictor of intermediate and long-term oncological outcomes after radical prostatectomy, and whether PTEN status predicts response to androgen deprivation therapy. In a retrospective analysis of 77 men treated by radical prostatectomy who underwent diagnostic biopsy between 1992-2006, biopsy samples were stained for PTEN expression by the PREZEON assay with >10% staining reported as positive. Cox proportional hazards and log-rank models were used to assess the correlation between PTEN loss and clinical outcomes. During a median follow-up period after radical prostatectomy of 8.8 years, 39 men (51%) developed biochemical recurrence, four (5%) had castration-resistant prostate cancer, two (3%) had metastasis and two (3%) died from prostate cancer. PTEN loss was not significantly associated with biochemical recurrence (hazard ratio 2.1, 95% confidence interval 0.9-5.1, P = 0.10), but significantly predicted increased risk of castration-resistant prostate cancer, metastasis and prostate cancer-specific mortality (all log-rank, P < 0.0001), and time from androgen deprivation therapy to castration-resistant prostate cancer (log-rank, P = 0.003). No patient without PTEN loss developed metastases or died from prostate cancer. PTEN loss at the time of biopsy seems to predict time to development of metastasis, prostate cancer-specific mortality and, for the first time, castration-resistant prostate cancer and response to androgen deprivation therapy after radical prostatectomy. If confirmed by larger studies, this would support the use of PTEN loss as an early marker of aggressive prostate cancer.

947: Italianity is associated with lower risk of prostate cancer mortality in Switzerland

947: Italianity is associated with lower risk of prostate cancer mortality in Switzerland

Cancer Mortality by Country of Birth, Sex, and Socioeconomic Position in Sweden, 1961–2009

In 2010, cancer deaths accounted for more than 15% of all deaths worldwide, and this fraction is estimated to rise in the coming years. Increased cancer mortality has been observed in immigrant populations, but a comprehensive analysis by country of birth has not been conducted. We followed all individuals living in Sweden between 1961 and 2009 (7,109,327 men and 6,958,714 women), and calculated crude cancer mortality rates and age-standardized rates (ASRs) using the world population for standardization. We observed a downward trend in all-site ASRs over the past two decades in men regardless of country of birth but no such trend was found in women. All-site cancer mortality increased with decreasing levels of education regardless of sex and country of birth (p for trend <0.001). We also compared cancer mortality rates among foreign-born (13.9%) and Sweden-born (86.1%) individuals and determined the effect of education level and sex estimated by mortality rate ratios (MRRs) using multivariable Poisson regression. All-site cancer mortality was slightly higher among foreign-born than Sweden-born men (MRR = 1.05, 95% confidence interval 1.04–1.07), but similar mortality risks was found among foreign-born and Sweden-born women. Men born in Angola, Laos, and Cambodia had the highest cancer mortality risk. Women born in all countries except Iceland, Denmark, and Mexico had a similar or smaller risk than women born in Sweden. Cancer-specific mortality analysis showed an increased risk for cervical and lung cancer in both sexes but a decreased risk for colon, breast, and prostate cancer mortality among foreign-born compared with Sweden-born individuals. Further studies are required to fully understand the causes of the observed inequalities in mortality across levels of education and countries of birth.

Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study

Objective To determine the relative risks of prostate cancer incidence, metastasis, and mortality associated with screening by serum prostate specific antigen (PSA) levels at age 60. Design Population based cohort...

Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI&lt;25 kg/m2), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI &gt;40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p&lt;0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p&lt;0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment.

Type 2 diabetes and the risk of mortality among patients with prostate cancer

The aim of this study was to determine whether type 2 diabetes is associated with the incidence of prostate cancer mortality and all-cause mortality. This study was conducted by linking four databases from the United Kingdom: the National Cancer Data Repository, the Clinical Practice Research Datalink, the Hospital Episodes Statistics database, and the Office for National Statistics database. The cohort consisted of men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 December 2009, followed until 1 October 2012. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95 % confidence intervals (CIs) of prostate cancer mortality and all-cause mortality comparing patients with to without type 2 diabetes. All models were adjusted for a number of potential confounders, which included excessive alcohol use, smoking, comorbidities, and prostate cancer-related variables. The cohort consisted of 11,920 patients, which included 1,132 (9.5 %) with preexisting type 2 diabetes. During a mean follow-up of 4.7 (SD 3.0) years, there were 3,605 deaths (incidence rate: 6.4 %/year) including 1,792 from prostate cancer (incidence rate: 3.3 %/year). Type 2 diabetes was associated with a 23 % increased risk of prostate cancer mortality (HR 1.23, 95 % CI 1.04-1.46) and a 25 % increased risk in all-cause mortality (HR 1.25, 95 % CI 1.11-1.40). The results of this large population-based study indicate that type 2 diabetes is associated with an increased risk of prostate cancer mortality and all-cause mortality, which may signal an association between hyperinsulinemia or other diabetes-associated metabolic derangements and cancer aggressivity.

Use of Statins and the Risk of Death in Patients With Prostate Cancer

To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Fat intake after diagnosis and risk of lethal prostate cancer and all-cause mortality.

Nearly 2.5 million men currently live with prostate cancer in the United States, yet little is known about the association between diet after diagnosis and prostate cancer progression and overall mortality. To examine postdiagnostic fat intake in relation to lethal prostate cancer and all-cause mortality. Prospective study of 4577 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2010). Postdiagnostic intake of saturated, monounsaturated, polyunsaturated, trans, animal, and vegetable fat. Lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality. We observed 315 events of lethal prostate cancer and 1064 deaths (median follow-up, 8.4 years). Crude rates per 1000 person-years for lethal prostate cancer were as follows (highest vs lowest quintile of fat intake): 7.6 vs 7.3 for saturated, 6.4 vs 7.2 for monounsaturated, 5.8 vs 8.2 for polyunsaturated, 8.7 vs 6.1 for trans, 8.3 vs 5.7 for animal, and 4.7 vs 8.7 for vegetable fat. For all-cause mortality, the rates were 28.4 vs 21.4 for saturated, 20.0 vs 23.7 for monounsaturated, 17.1 vs 29.4 for polyunsaturated, 32.4 vs 17.1 for trans, 32.0 vs 17.2 for animal, and 15.4 vs 32.7 for vegetable fat. Replacing 10% of energy intake from carbohydrate with vegetable fat was associated with a lower risk of lethal prostate cancer (hazard ratio [HR], 0.71; 95% CI, 0.51-0.98; P = .04) and all-cause mortality (HR, 0.74; 95% CI, 0.61-0.88; P = .001). No other fats were associated with lethal prostate cancer. Saturated and trans fats after diagnosis (replacing 5% and 1% of energy from carbohydrate, respectively) were associated with higher all-cause mortality (HR, 1.30 [95% CI, 1.05-1.60; P = .02] and 1.25 [95% CI, 1.05-1.49; P = .01], respectively). Among men with nonmetastatic prostate cancer, replacing carbohydrates and animal fat with vegetable fat may reduce the risk of all-cause mortality. The potential benefit of vegetable fat for prostate cancer-specific outcomes merits further research.

Prediagnostic circulating markers of inflammation and risk of prostate cancer

Accruing evidence suggests that inflammation plays a role in prostate carcinogenesis. However, studies evaluating this association using C-reactive protein (CRP) and interleukin-6 as markers of inflammation have reported conflicting results. We investigated the associations of three common markers of inflammation (CRP, fibrinogen and leukocyte count) with the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow-up period of 24 years (21-26 years), 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. We investigated the associations between the markers and the risk of prostate cancer using Cox proportional hazards model, adjusting for potential confounders. Elevated prediagnostic leukocyte count was associated with an increased risk of prostate cancer. In multivariable adjusted model, the relative risk of prostate cancer among men in the highest tertile of leukocyte count compared to men in the lowest tertile was 1.60 (95% confidence interval [CI] = 1.10-2.29, p-trend = 0.01). Circulating CRP and fibrinogen were not associated with increased risk. The corresponding relative risks for elevated CRP and fibrinogen concentrations were 1.08 (95% CI: 0.74-1.60, p-trend = 0.56) and 1.25 (95% CI: 0.87-1.81, p-trend = 0.14), respectively. Men with elevated leukocyte counts had a 2.57-fold (95% CI: 0.99-6.79) increased risk of prostate cancer mortality. The increased risk associated with elevated leukocyte counts warrants confirmation in other studies. Larger studies should consider combining at least two markers or using an inflammation score derived from many inflammatory markers to evaluate prostate cancer risk.

Coffee and risk of prostate cancer incidence and mortality in the Cancer of the Prostate in Sweden Study

Coffee intake has recently been associated with significantly lower risk of lethal and advanced prostate cancer in a US population. We studied the association between coffee and prostate cancer risk in the population-based case-control study Cancer of the Prostate in Sweden. Dietary data were available for 1,499 cases and 1,112 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low categories of coffee intake using logistic regression. We studied overall prostate cancer risk as well as risk of fatal, advanced, localized, high-grade, grade 7, and low-grade disease. Mean coffee intake was 3.1 cups per day among both cases and controls. Coffee intake was not associated with overall prostate cancer risk. Risk of fatal prostate cancer was inversely, but not statistically significantly, associated with coffee intake, with an odds ratio of 0.64 [95% confidence interval (CI) 0.34-1.19, p value for linear trend=0.81] for men consuming greater than 5 cups per day compared to men drinking less than 1 cup per day. The highest intake of coffee was associated non-significantly with lower risk of advanced disease (OR=0.73, 95% CI 0.41-1.30, p trend=0.98) and associated significantly with lower risk of high-grade cancer (Gleason 8-10; OR=0.50, 95% CI 0.26-0.98, p trend=0.13). Risk of localized, grade 7, and low-grade cancers was not associated with coffee intake. This study provides some support of an inverse associationbetween coffee and lethal and high-grade prostate cancer.

Aspirin use in prostate cancer and the risk of death and metastasis.

1518 Background: There has been recent interest in the role of aspirin in preventing prostate cancer outcomes, but data remain limited. The objective was to determine whether the use of aspirin after prostate cancer diagnosis is associated with a decreased risk of prostate cancer mortality, distant metastasis and all-cause mortality in men newly-diagnosed with prostate cancer. Methods: A population-based cohort of men diagnosed with non-metastatic prostate cancer between 01/04/1998 and 31/12/2009 was identified using the UK Clinical Practice Research Datalink, including the Cancer Registry. All men were followed until death, distant metastasis, or 01/10/2012. A nested case-control analysis was performed where, for each case with an incident outcome event, up to 10 controls were matched on age, year of diagnosis and duration of follow-up. Exposure was defined as aspirin use during the matched follow-up period. Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusted for covariates and considering effect modification by aspirin use prior to prostate cancer diagnosis. Results: The cohort included 13,396 prostate cancer patients, followed for 3.9 (SD=2.4) years during which 4,425 deaths occurred, including 2,315 from prostate cancer, and 2,344 cases of distant metastasis. Aspirin use was associated with an increased risk of prostate cancer mortality (RR 1.36, 95% CI 1.18-1.55) and all-cause mortality (RR 1.33, 95% CI 1.21-1.47), but not distant metastasis (RR 1.09, 95% CI 0.94-1.27). The increased risks were limited to patients who did not use aspirin before diagnosis, for both prostate cancer mortality (RR 1.69, 95% CI 1.43-2.00) and all-cause mortality (RR 1.62, 95% CI 1.44-1.82), while those who used aspirin before diagnosis did not have increased risks (RR 0.93, 95% CI 0.76-1.15 and RR 0.98, 95% CI 0.85-1.13, respectively). Conclusions: The use of aspirin after prostate cancer diagnosis is not associated with a decreased risk of prostate cancer outcomes. Although increased risks were observed for all-cause and prostate cancer mortality, these effects were exclusively driven by new-users of aspirin, suggesting that aspirin use in these patients was likely related to disease progression.