Cumulative Incidence Of Prostate Cancer Research Articles

Risk of prostate cancer in patients with inflammatory bowel disease: a nationwide cohort study in South Korea.

Several studies have suggested an association between inflammatory bowel disease (IBD) and the risk of prostate cancer development. However, these findings are inconsistent, and studies based on Asian populations are limited. We compared the risk of prostate cancer according to IBD status using the Korean National Health Insurance Service database. A population-based retrospective cohort of age-matched 59,044 non-IBD patients and 14,761 IBD patients between January 2009 and December 2011 was analyzed up to December 2017. The risk of prostate cancer was compared between patients with IBD and controls using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. During a median follow-up of 6 years, the incidence rate of prostate cancer was 264 per 100,000 person-years in non-IBD patients and 242 per 100,000 person-years in patients with IBD. IBD status was not associated with the risk of prostate cancer compared to non-IBD [adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI): 0.80-1.08, p = 0.32). The cumulative incidence of prostate cancer did not differ by IBD status (non-IBD patients versus IBD patients: log-rank p = 0.27; non-IBD patients versus ulcerative colitis versus Crohn's disease: log-rank p = 0.42). In multivariate analysis, age was an independent risk factor for the development of prostate cancer (HR 1.03, 95% CI: 1.02-1.03, p < 0.001). In our population-based study, IBD status was not associated with the risk of prostate cancer.

PD65-02 IMPACT OF PROSTATE-SPECIFIC ANTIGEN (PSA) SCREENING INTENSITY ON PROSTATE CANCER DIAGNOSIS IN A RACIALLY DIVERSE HEALTHCARE SYSTEM OVER A 25-YEAR PERIOD

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-02 IMPACT OF PROSTATE-SPECIFIC ANTIGEN (PSA) SCREENING INTENSITY ON PROSTATE CANCER DIAGNOSIS IN A RACIALLY DIVERSE HEALTHCARE SYSTEM OVER A 25-YEAR PERIOD Deepansh Dalela, Marcus Jamil, Akshay Sood, Nikola Rakic, Jacob Keeley, Patrick Etta, Brett Friedman, Craig Rogers, Mani Menon, and Firas Abdollah Deepansh DalelaDeepansh Dalela More articles by this author , Marcus JamilMarcus Jamil More articles by this author , Akshay SoodAkshay Sood More articles by this author , Nikola RakicNikola Rakic More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Patrick EttaPatrick Etta More articles by this author , Brett FriedmanBrett Friedman More articles by this author , Craig RogersCraig Rogers More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The optimal frequency of PSA screening remains undefined, with the US-based Prostate, Lung, Colorectal and Ovarian (PLCO) trial defining PSA testing every 1-2 years as ‘routine’ screening. In the context of evolving (and often conflicting) guidelines for PSA screening, it remains unknown if ‘routine’ screening affects prostate cancer (PCa) diagnosis differently compared to less frequent PSA testing METHODS: Henry Ford Health System is a large, racially diverse integrated healthcare system in Southeast Michigan, USA. Over the study period (1995-2019), Men aged 45+ without a prior PCa diagnosis who had at-least one PSA test and remained in the system for at-least 6 years or were diagnosed with PCa within 2 years were included in our analyses. Screening intensity was assessed based on a 5-year window: routine screening (at least one PSA test q1-2 years), occasional (at-least one test q3 yearly) and sporadic (no test for three consecutive years), averaged over the duration of the follow up in the study. Outcomes variables were time to diagnosis of PCa, PSA, incidence of clinical nodal and metastatic disease at diagnosis. RESULTS: Overall, 52,343 (34.6%), 50042 (33.1%) and 48.966 (32.4%) men were included in the sporadic, occasional and routine PSA screening groups, respectively, of which 34,623 (22.9%) were Black. Median (IQR) age for first PSA testing was 56.8 (50.3-66.5) years, and cumulative incidence of PCa was 2.3%, 3.8% and 6.2% for sporadic, occasional and routine groups respectively. Compared to men undergoing routine screening, men in occasional and sporadic groups had significantly higher median PSA (5.4 vs. 6.1 vs 7.2 ng/mL), clinical N+ (1.2% vs. 1.8% vs. 3.8%) and metastatic disease (6.5% vs. 9.5% vs. 15.4%) at diagnosis (Table 1, all p<0.001). CONCLUSIONS: Results from a large, racially diverse US-based healthcare system showed that only about one-third of the population underwent routine PSA screening (every 1-2 years), as defined by the PLCO study. Further, men undergoing routine screening had more favorable tumor characteristics at diagnosis and lower incidence of metastatic disease, highlighting its oncological benefit compared to opportunistic screening. Source of Funding: n/a © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1151-e1152 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Deepansh Dalela More articles by this author Marcus Jamil More articles by this author Akshay Sood More articles by this author Nikola Rakic More articles by this author Jacob Keeley More articles by this author Patrick Etta More articles by this author Brett Friedman More articles by this author Craig Rogers More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

Estimating the rate of overdiagnosis with prostate cancer screening: evidence from the Finnish component of the European Randomized Study of Screening for Prostate Cancer.

Screening for prostate cancer may have limited impact on decreasing prostate cancer-related mortality. A major disadvantage is overdiagnosis, whereby lesions are identified that would not have become evident during the man's lifetime if screening had not taken place. The present study aims to estimate the rate of overdiagnosis using Finnish data from the European randomized trial of prostate cancer screening. We used data from 80,149 men randomized to a screening or a control group, distinguishing four birth cohorts. We used the "catch-up method" to identify when the difference in the cumulative incidence of prostate cancer between the screening and control groups had stabilized, implying that the screening has no further effect. We define the overdiagnosis rate to be the relative excess cumulative incidence in the screened group at that point. As an independent method, we also examined the diagnosis rates of T1c tumors as an indicator of early tumors detected by PSA. The estimates of overdiagnosis rates from the catch-up method using the full period of available follow-up ranged between cohorts from 2.3% to 15.4%, and the T1c analysis gave very similar results. Some overdiagnosis has occurred, but there is uncertainty about its extent. A long follow-up is required to demonstrate the full impact of screening. We evaluated the overdiagnosis rates at a population level, associated with being offered screening, taking account of contamination (screening among the controls). The overall evaluation of screening should incorporate mortality benefit, cost-effectiveness, and quality of life.

Risk stratification in men with a negative prostate biopsy: an interim analysis of a prospective cohort study.

To investigate whether a risk score for prostate cancer (PCa) lifetime risk can be used to optimise triaging of patients with a negative prostate biopsy, but under sustained suspicion of PCa. In this prospective clinical study, we included, and risk scored patients who had a PCa-negative transrectal ultrasonography (TRUS)-guided prostate biopsy, but elevated prostate-specific antigen (PSA), a suspicious prostate digital rectal examination and/or a positive family history (FH) of PCa. The risk score estimated individual lifetime risk of PCa, based on a polygenic risk score (33 single nucleotide polymorphisms), age, and FH of PCa. Patients were followed, under urological supervision, for up to 4years with annual controls, always including PSA measurements. Multiparametric magnetic resonance imaging (mpMRI) and/or prostate biopsy was performed at selected annual controls depending on risk score and at the urologist's/patient's discretion, which means that the follow-up differed based on the risk score. We included 429 patients. After risk scoring, 376/429 (88%) patients were allocated to a normal-risk group (<30% PCa lifetime risk) and 53/429 (12%) to a high-risk group (≥30% PCa lifetime risk). The high-risk group had significantly different follow-up, with more biopsy and mpMRI sessions compared to the normal-risk group. PCa was detected in 89/429 (21%) patients, with 67/376 (18%) patients diagnosed in the normal-risk group and 22/53 (42%) in the high-risk group. There was no statistically significant difference in the cumulative incidence of PCa between the normal-risk group and the high-risk group after 4years of follow-up. Currently, 67/429 (16%) patients are still being followed in this ongoing study. In a 4-year perspective, our PCa lifetime risk score did not demonstrate significant prognostic value for triaging patients, with a negative TRUS-guided biopsy and sustained suspicion of PCa.

Evaluation of a Multiethnic Polygenic Risk Score Model for Prostate Cancer.

Polygenic risk scores (PRSs) of common genetic variants have shown promise in prostate cancer risk stratification, but their validity across populations has yet to be confirmed. We evaluated a multiethnic PRS model based on 269 germline genetic risk variants (261 were available for analysis) using an independent population of 13 628 US men. The PRS was strongly associated with prostate cancer but not with any other disease. Comparing men in the top PRS decile with those at average risk (40%-60%), the odds ratio of prostate cancer was 3.89 (95% confidence interval = 3.24 to 4.68) for men of European ancestry and 3.81 (95% confidence interval = 1.48 to 10.19) for men of African ancestry. By age 85 years, the cumulative incidence of prostate cancer for European American men was 7.1% in the bottom decile and 54.1% in the top decile. This suggests that the PRS can be used to identify a substantial proportion of men at high risk for prostate cancer.

Digoxin lowers the incidence of prostate cancer: A nationwide population-based study.

In vitro studies have confirmed that cardiac glycosides can induce apoptosis in both hormone-dependent and -independent prostate cancer (PCa) cell lines. The aim of this study was to investigate the incidence of PCa among patients treated with and without digoxin using a nationwide population-based database in Taiwan. We retrieved data of men aged 30 years or older who were newly diagnosed with heart failure between January 1998 and December 2003 from the National Health Insurance program database in Taiwan. We divided the patients into digoxin users and non-digoxin users. Kaplan-Meier curves and Cox proportional hazard analysis were used to examine the risk of subsequent PCa between the digoxin and non-digoxin groups. The mean ± SD follow-up (years) periods in the digoxin and non-digoxin groups were 8.6 ± 1.78 and 8.3 ± 1.75, respectively. The cumulative incidence of PCa during the follow-up period was 3.5% (147/4233) in the non-digoxin group compared with 3.0% (65/2154) in the digoxin group. The log-rank test revealed that the digoxin group had a similar incidence of PCa to the non-digoxin group (p = 0.18). After adjusting for age, benign prostatic hyperplasia, and comorbidities, Cox proportional hazard regression analysis showed that digoxin was associated with a significantly decreased risk of developing PCa (hazard ratio, 0.74; 95% CI, 0.548-0.993; p = 0.045). Moreover, logistic regression analysis showed that the risk of PCa decreased with a longer duration of digoxin use during the study period compared to those who had never used digoxin (p = 0.043). The cardiac glycoside digoxin had significant effects on reducing the incidence of PCa in a time-dependent manner. Our findings may imply the potential application of cardiac glycosides in the prevention and management of PCa.

Prostate cancer risk assessment in men with an initial P.S.A. below 3 ng/mL: results from the Göteborg randomized population-based prostate cancer screening trial

Objective: To evaluate the long-term outcome of men with an initial prostate-specific antigen (PSA) level below 3 ng/mL and whether the free-to-total (F/T PSA) ratio is a useful prognostic marker in this range.Materials and methods: This study is based on 5,174 men aged 50–66 years, who in 1995–1996 participated in the first round of the Göteborg randomized screening trial (initial T-PSA level <3 ng/mL). These men were subsequently invited biennially for PSA and F/T PSA screening until they reached the upper age limit (on average 69 years). Biopsy was recommended if PSA ≥ 3 ng/mL.Results: After a median follow-up of 18.9 years, 754 men (14.6%) were diagnosed with prostate cancer (PC). The overall cumulative PC incidence was 17.2%. It increased from 7.9% among men with T-PSA of ≤0.99 ng/mL to 26.0% in men with T-PSA levels of 1–1.99 ng/mL and 40.3% in men between 2–2.99 ng/mL (p < 0.001). The initial PSA was also related to the incidence of Gleason ≥7 PC (3.7% vs 9.7% vs 10.9%) and PC death (0.3% vs 1.1% vs 1.5%). Adding F/T PSA did not improve PC prediction in terms of Harrell concordance index (base model 0.76 vs 0.76) nor improvement of the likelihood of the model (p = 0.371).Conclusions: Some men with initial PSA < 3 ng/mL will be diagnosed too late, despite participating in an organized screening program, indicating that prompt diagnosis is justified in these men. PC incidence and risk of PC death was associated with PSA., but F/T PSA had no predictive value.

Association between gallbladder stone disease and prostate cancer: A nationwide population-based study.

ObjectivesChronic inflammation and abnormal cholesterol metabolism are involved in the pathogenesis of gallbladder stone disease (GSD) and that of prostate cancer in experimental studies. We assessed the association between GSD and prostate cancer in this population-based study.ResultsThe cumulative incidence of prostate cancer (log-rank test: P <.001) and the risk of prostate cancer (1.64 vs 1.14 per 10 000 person-y, adjusted hazard ratio [aHR] = 1.30, 95% confidence interval [CI] = 1.22-1.39) were greater in the patients with GSD than in those without GSD. Furthermore, the risk of prostate cancer increased with the time of follow-up after a diagnosis of GSD, particularly after 9 years of follow-up (aHR = 1.95, 95% CI = 1.74-2.19).Materials and MethodsWe identified 9496 patients who were diagnosed with GSD between 1998 and 2011 from Taiwan's Longitudinal Health Insurance Database 2000 as the study cohort. We randomly selected 37 983 controls from the non-GSD population and used frequency matching by age, sex, and index year for the control cohort. All patient cases were followed until the end of 2011 to measure the incidence of prostate cancer.ConclusionGSD is associated with an increased risk of prostate cancer, and the risk increases with the time of follow-up after a diagnosis of GSD.

The Effect of Start and Stop Age at Screening on the Risk of Being Diagnosed with Prostate Cancer

We investigated the effect of age and number of screens on the risk of prostate cancer diagnosis. Since 1995 the Göteborg randomized population based prostate cancer screening trial has invited men biennially for prostate specific antigen testing, until the upper age limit of 70 years. Men with a prostate specific antigen above the threshold of 2.5 ng/ml were recommended further evaluation including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born between 1930 and 1943 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3 to 9 invitations). The cumulative incidence of prostate cancer was calculated using standard methods. Of the 3,488 (38%) complete attendees 667 were diagnosed with prostate cancer (followup 1995 to June 30, 2014). At age 70 years there was no significant difference in prostate cancer risk among those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of prostate cancer diagnosis increased dramatically with age, and was 7.9% at age 60, 15% at age 65 and 21% at age 70 for men who had been screened 4 or more times. There was no clear association between risk of prostate cancer and the number of screens. Starting screening at an early age appears to advance the time of prostate cancer diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with prostate cancer.

A positive family history as a risk factor for prostate cancer in a population-based study with organised prostate-specific antigen screening: results of the Swiss European Randomised Study of Screening for Prostate Cancer (ERSPC, Aarau).

To assess the value of a positive family history (FH) as a risk factor for prostate cancer incidence and grade among men undergoing organised prostate-specific antigen (PSA) screening in a population-based study. The study cohort comprised all attendees of the Swiss arm of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with systematic PSA level tests every 4 years. Men reporting first-degree relative(s) diagnosed with prostate cancer were considered to have a positive FH. Biopsy was exclusively PSA triggered at a PSA level threshold of 3 ng/mL. The primary endpoint was prostate cancer diagnosis. Kaplan-Meier and Cox regression analyses were used. Of 4 932 attendees with a median (interquartile range, IQR) age of 60.9 (57.6-65.1) years, 334 (6.8%) reported a positive FH. The median (IQR) follow-up duration was 11.6 (10.3-13.3) years. Cumulative prostate cancer incidence was 60/334 (18%, positive FH) and 550/4 598 (12%, negative FH) [odds ratio 1.6, 95% confidence interval (CI) 1.2-2.2, P = 0.001). In both groups, most prostate cancer diagnosed was low grade. There were no significant differences in PSA level at diagnosis, biopsy Gleason score or Gleason score on pathological specimen among men who underwent radical prostatectomy between both groups. On multivariable analysis, age (hazard ratio [HR] 1.04, 95% CI 1.02-1.06), baseline PSA level (HR 1.13, 95% CI 1.12-1.14), and FH (HR 1.6, 95% CI 1.24-2.14) were independent predictors for overall prostate cancer incidence (all P < 0.001). Only baseline PSA level (HR 1.14, 95% CI 1.12-1.16, P < 0.001) was an independent predictor of Gleason score ≥7 prostate cancer on prostate biopsy. The proportion of interval prostate cancer diagnosed in-between the screening rounds was not significantly different. Irrespective of the FH status, the current PSA-based screening setting detects the majority of aggressive prostate cancers and missed only a minority of interval cancers with a 4-year screening algorithm. Our results suggest that men with a positive FH are at increased risk of low-grade but not aggressive prostate cancer.

MP86-07 ASSOCIATION OF METFORMIN USE WITH PROSTATE CANCER INCIDENCE IN A PROSPECTIVE SCREENING TRIAL (ERSPC AARAU)

INTRODUCTION AND OBJECTIVES: There is conflicting data regarding the effect of the oral antidiabetic drug metformin on prostate cancer (PCa) incidence and mortality. We aimed to assess the effect of metformin on PCa incidence and mortality in men participating in a prospective, population-based screening trial. METHODS: Data of men who underwent PSA-screening in our population-based screening trial (ERSPC Aarau) were analysed. Information on metformin exposure before biopsy was obtained by a selfadministered questionnaire. Cox regression analysis was used to examine the relationship between covariates and PCa incidence. RESULTS: Overall, 4,314 men were observed during a mean follow-up time of 7.3 ( SD2.3) years. Mean age at baseline was 65.5 years (65.5 SD 4.4). Overall, n1⁄4150 (3.5%) men used metformin [metfþ] at baseline. Of those, 80% (88 of 110) who were actively screened during follow-up visit were still on metformin after 4 years whereas 105 men had new [metfþ] exposure. Mean baseline PSAlevels were comparable between both groups ([metfþ] 1.6ng/ml 2.4 vs. [metf-] 1.8ug/l 2.2, p1⁄40.4) while f/t-ratio was slightly higher in metformin users ([metfþ] 30.7% 10.9 vs. [metf-] 27.3% 10.9, p1⁄40.01). Overall, n1⁄4372 (8.6%) PCa cases were detected. Neither cumulative PCa incidence (n1⁄411; 7.3% [metfþ] vs. n1⁄4361 8.7% [metf-]; p1⁄40.5) nor d’Amico risk groups were significantly different between both groups. On multivariate analysis, only increasing baseline PSA (HR 1.11, 95%CI 1.09-1.13; p<0.0001) achieved an independent predictor status for PCa detection. An increasing freetotal PSA ratio was an independent predictor for a decreased risk for PCa detection during follow-up (HR 0.95, 95%CI 0.94-0.96; p<0.0001). Among 150 [metfþ] and 4164 [metf-] men, 1 (0.7%) and 1 (0.02) died from PCa (OR 27.94, 95%CI 1.73-448.84; p<0.0001) whereas 26 (17.3%) and 329 (7.9%) (unadjusted OR 2.50, 95%CI 1.59-3.82; p<0.0001) died from other causes during follow-up, respectively. In a competing risk analysis, [metfþ] exposure among men who died during follow-up had no influence on PCa incidence (SHR 0.91, 95%CI 0.50-1.66; p1⁄40.77). CONCLUSIONS: No significant differences in PSA levels or PCa incidence and grade were observed between metformin users and non users. The slightly higher f/t-ratio did not result in lower PCa detection rate. However, metformin users were at significantly higher risk to die from any cause. This underlines the idea of a risk-based strategy of early PCa detection with recognizing diabetes mellitus as an important competing comorbidity.

Abstract LB-195: A double-blind randomized controlled multisite trial evaluating tissue effects of preoperative finasteride in clinically organ-confined prostate cancer: Pathologic outcomes.

Abstract Background: The Prostate Cancer Prevention Trial (PCPT) showed a relative reduction of 24.8% in cumulative incidence of prostate cancer (PC) in finasteride-treated men (18.4 v 24.4%; p&amp;lt;.001). However, high-grade cancers (Gleason score [GS] ≥7) were more commonly detected in men receiving finasteride than placebo (6.4 v 5.1%; p=.005), an effect of uncertain significance. We therefore undertook a study to determine differences between finasteride-exposed and -unexposed (placebo/control) cancers in the expression of a preselected molecular signature shown to distinguish Gleason grade (GG) 3 from GG 4 untreated tumors. Methods: This 4-site presurgical trial was in men with clinically organ-confined PC (cT1c/T2; GS 6 or 7; prostate-specific antigen [PSA] &amp;lt;10 ng/mL) randomly assigned to treatment with 5 mg finasteride or placebo daily for 4-6 wk prior to prostatectomy. At baseline and at surgery, PSA, testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) levels were measured in men who opted to donate blood for research. We used a standard method to handle radical prostatectomy (RP) specimens, including mapping of tumor foci to document relevant morphologic data. Results: In all, 210 patients consented, 204 were randomized, 183 were evaluable for detailed pathologic outcomes, and 163 were evaluable for PSA and hormone levels. Median age was 60 (45-73) yr. Median treatment time was 28 (10-43) days. Median prostate total tumor volume (TV) was 0.9 (0-10.4) cc, and peripheral zone TV, 0.6 (0-9.3) cc. Biopsy (Bx) GS, GS upgrade between Bx and RP, specimen GS/GG, total cancer foci, zonal origin of dominant cancer, and median total and PZ TV were similar in the 2 treatment arms (A v B). Post-treatment, median PSA was significantly lower (3.2 v 5.2 ng/mL; p&amp;lt;.001); testosterone, significantly higher (391 v 325 ng/dL; p=.021); and DHT, significantly lower (10 v 27 ng/dL; p&amp;lt;.001) in arm A than in arm B. No differences were noted in E1 and E2 levels. Biomarker analysis of a preselected molecular signature is under way; unblinding awaits completion of biomarker analysis. Conclusions: No significant difference in GS distribution was observed between the two groups after short-term exposure to finasteride or placebo. Modulation of PSA, T, and DHT levels occurred in a statistically significant uneven distribution by study arm. Molecular signature characterization has been completed, and the planned analysis of associations is under way. The findings are expected to provide insight into the reported grade effect attributed to finasteride. (This work was supported in part by NCI contract N01-CN-35159.) Citation Format: Jeri Kim, John W. Davis, Eric A. Klein, Cristina Magi-Galluzzi, Yair Lotan, John F. Ward, Louis L. Pisters, Joseph W. Basler, Curtis A. Pettaway, Elsa M. Li Ning Tapia, Xuemei Wang, Kim-Anh Do, Jack Lee, Lana A. Vornik, Joe Tangrea, Howard L. Parnes, Scott M. Lippman, Ian M. Thompson, Powel H. Brown, Patricia Troncoso, Christopher J. Logothetis. A double-blind randomized controlled multisite trial evaluating tissue effects of preoperative finasteride in clinically organ-confined prostate cancer: Pathologic outcomes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-195. doi:10.1158/1538-7445.AM2013-LB-195

87IN - Prostate Cancer: What are the Prospects and Guidelines for Screening and Prevention?

ABSTRACT The European Randomized Study of Screening for Prostate Cancer (ERSPC) showed a significant prostate cancer mortality reduction in the screening group of 21% after a median follow-up of 11 years, and of 29% in screened men when adjusted for selection bias. However, PSA screening is associated with considerable unfavorable effects. In the ERSPC screening group, cumulative incidence of prostate cancer was 7.4%, versus 5.1% in the control group. A proportion of the screen-detected tumors (10-56%) would never have led to clinical symptoms but these over-diagnosed cancers are frequently treated with associated risks of adverse effects. Furthermore, because of a long lead-time, estimated 5-12 years, men have to live longer with those effects. Two specific studies on quality of life after prostate cancer treatment have been performed for men participating in Rotterdam and Sweden. Pre-operatively 1-2% of the men were incontinent and 31-40% impotent. After 18-52 months 6-16% of the radical prostatectomy patients and 3% of the radiation therapy patients were incontinent. Six to 52 months after radical prostatectomy, 83-88% of pre-operatively potent men became impotent, compared with 42-66% of the men receiving radiation therapy. In this lecture the effects of screening strategies on prostate cancer mortality and quality of life will be quantified, using the well-validated MISCAN-model, developed by our institute, and hereby using results from the ERSPC. The implications of our results are that the benefit of PSA screening is diminished by loss of QALYs, that is dependent primarily on post-diagnosis long-term utility assumptions. Longer follow-up data from both the ERSPC and quality of life and cost-effectiveness analyses are essential for making universal recommendations regarding screening, but it is possible that limited testing of middle-aged men with relatively long intervals is a cost-effective public health policy. Disclosure The author has declared no conflicts of interest.

Optimal prostate-specific antigen screening interval for prostate cancer

To identify the optimal interval for repeat prostate-specific antigen (PSA) testing to screen for prostate cancer in healthy adults. A retrospective cohort study was conducted on 7332 healthy males without prostate cancer at baseline from 2005 to 2008. Participants underwent annual health checkups including PSA testing at the Center for Preventive Medicine in Japan. Participants with high PSA (≥ 4.0 ng/ml) underwent further examination for prostate cancer. A subgroup analysis was conducted age group (<50 years, ≥ 50 years). Mean age was 50 years. Mean PSA at baseline was 1.2 ng/ml. In over 50-year group, for those with initial PSA of <1.0, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml at baseline, the 3-year cumulative incidence of prostate cancer was 0%, 0.1%, 0.3%, and 5.7%, respectively. No prostate cancer was identified in those <50 years, regardless of PSA level. If PSA screening is recommended, males >50 years with PSA of 3.0-3.9 ng/ml at baseline should undergo rescreening at 2 years. For men with PSA <3.0 ng/ml, PSA rescreening at intervals of ≥ 3 years is appropriate. PSA screening may not be indicated in males of <50 years of age.

StatBite Cumulative Incidence of Prostate Cancer (Placebo Group vs. Vitamin E Alone)

StatBite Cumulative Incidence of Prostate Cancer (Placebo Group vs. Vitamin E Alone)

The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes

Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration. In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS. Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF]. The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer.

Copy number variation in glutathione-S-transferase T1 and M1 predicts incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer in the general population

Glutathione-S-transferase T1 (GSTT1) and GSTM1 detoxify carcinogens and thus potentially contribute to inter-individual susceptibility to cancer. We determined the ability of GST copy number variation (CNV) to predict the risk of cancer in the general population. Exact copy numbers of GSTT1 and GSTM1 were measured by real-time PCR in 10 247 individuals, of whom 2090 had cancer. In men, the cumulative incidence of prostate cancer increased and the cumulative 5-year survival decreased with decreasing GSTT1 copy numbers (trends=0.02). The hazard ratios (HRs) (95% CIs) for prostate cancer and for death after prostate cancer diagnosis were, respectively, 1.2 (0.8-1.8) and 1.2 (0.6-2.1) for GSTT1*1/0, and 1.8 (1.1-3.0) and 2.2 (1.1-4.4) for GSTT1*0/0 versus GSTT1*1/1. In women, the cumulative incidence of corpus uteri cancer increased with decreasing GSTT1 copy numbers (trend=0.04). The HRs for corpus uteri cancer were, respectively, 1.8 (1.0-3.2) and 2.2 (1.0-4.6) for GSTT1*1/0 and GSTT1*0/0 versus GSTT1*1/1. Finally, the cumulative incidence of bladder cancer increased, and the cumulative 5-year survival decreased, with decreasing GSTM1 copy numbers (P=0.03-0.05). The HRs for bladder cancer were, respectively, 1.5 (0.7-3.2) and 2.0 (0.9-4.3) for GSTM1*1/0 and GSTM1*0/0 versus GSTM1*1/1. The HR for death after bladder cancer diagnosis was 1.9 (1.0-3.7) for GSTM1*0/0 versus GSTM1*1/0. In conclusion, exact CNV in GSTT1 and GSTM1 predict incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer.

Age at Diagnosis and Age at Death in Familial Prostate Cancer

A family history of prostate cancer is associated with a higher risk for prostate cancer to first-degree relatives. If greater surveillance of men at familial risk is considered to be useful, population-based estimates of the differences in the age at diagnosis between familial and sporadic prostate cancer cases are needed. The men in the nationwide Swedish Family-Cancer Database were classified according to the number and type of affected first-degree relatives (father or brother) and according to the relative's age at diagnosis. The cumulative incidence of prostate cancer and cumulative prostate cancer-specific mortality were estimated using a stratified Cox model. The cumulative incidence was highest for men with multiple affected first-degree relatives, and it was higher for brothers than for sons of prostate cancer patients. The age to reach the same cumulative incidence as the general population at age 55 years decreased with decreasing age at diagnosis of the relative, ranging from 48.7 years (father diagnosed before 60 years of age) to 53.7 years (father diagnosed after 82 years of age). Prostate cancer-specific mortality was also related to the number and type of affected relatives but there was no clear evidence for a dependency on the age at diagnosis of the relative. Men with a father or a brother affected by prostate cancer are diagnosed and die at earlier ages than men without a family history of prostate cancer. This study should encourage further analysis in order to assess the risks and benefits of screening for prostate cancer in men at higher risk.

Screening and Prostate-Cancer Mortality in a Randomized European Study

The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)

Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia

Objectives To examine the rate of prostate cancer detection in three large randomized placebo-controlled benign prostatic hyperplasia trials of dutasteride. Dutasteride, which lowers serum dihydrotestosterone more than 93% by inhibiting type 1 and type 2 5-alpha-reductase, is effective in the treatment of benign prostatic hyperplasia. However, its effect on the development of prostate cancer is unknown. Methods A total of 4325 men with benign prostatic hyperplasia but without a history, or evidence, of prostate cancer, and a serum prostate-specific antigen level of 1.5 to 10 ng/mL, were randomized to 0.5 mg/day dutasteride or placebo for 24 months. The prostate cancer detection rates for subjects were determined by non-protocol-mandated biopsies, either during the double-blind phase of the study or during the first 3 months of the open-label extension. A follow-up questionnaire was administered to a subset of consenting subjects to ascertain the number, outcomes, and reasons for the prostate biopsies. Results The cumulative incidence of prostate cancer as an adverse event was significantly lower in the dutasteride versus placebo group at 24 months (1.1% versus 1.9%, P = 0.025) and 27 months (1.2% versus 2.5%, P = 0.002). There were no differences in the diagnosis rates of prostate cancer during the first 15 months, after which time the detection rate of prostate cancer increased in the placebo group and remained low in the dutasteride group. Conclusions Prostate cancer detection was significantly lower in subjects randomized to dutasteride compared with the placebo group. These results have prompted the initiation of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study, which was designed and powered to test the hypothesis that treatment with dutasteride decreases the incidence and progression of prostate cancer.