ERSPC (European Randomized Study of Screening for Prostate Cancer)
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Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial.

Journal International journal of cancer
Year 2002
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Cet article est inclus dans 1 Systematic review Systematic reviews (1 reference)

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Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.

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Specific features of the Italian section of the ERSPC.

Journal BJU international
Year 2003
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Cet article est inclus dans 1 Systematic review Systematic reviews (1 reference)

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Contamination by opportunistic screening in the European Randomized Study of Prostate Cancer Screening.

Journal BJU international
Year 2003
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Cet article est inclus dans 2 Systematic reviews Systematic reviews (2 references)

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Features and preliminary results of prostate cancer screening in Canton Aargau, Switzerland.

Journal BJU international
Year 2003
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Cet article est inclus dans 1 Systematic review Systematic reviews (1 reference)

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OBJECTIVE: To report the results from Switzerland's participation in the ERSPC from 1998; importantly, epidemiological data showed that Switzerland has one of the highest rates of morbidity and mortality from prostate cancer in the world. The local study protocol was accepted by the ethical committee and after the successful pilot study phase, the centre joined the ERSPC. SUBJECTS AND METHODS: From September 1998 to June 2003 10 300 men accepted an invitation for the study and were then randomized 1:1 into an active screening arm (assessed by testing prostate-specific antigen, PSA) or a control group (no intervention). The re-screening interval is 4 years and is ongoing (beginning in September 2002). The study protocol includes offering a prostate biopsy when the total PSA is >3.0 ng/mL (the main study protocol in agreement with ERSPC requirements) or when the total PSA is 1-3 ng/mL and the free-to-total PSA ratio <20% (side study protocol). RESULTS: During the first 3 years of screening 3562 men aged 55-70 years were screened; 395 (11.1%) of all participants had a total PSA of >3 ng/mL and 251 (7.4%) were eligible for the side-study. In all, 599 (17.2%) of 3562 accepted a prostate biopsy (93% of 646); 120 cases of prostate cancer were detected (3.4% detection rate). The incidence was 2.5% in main study group (positive predictive value, PPV, 24%) and 0.9% in side study group (PPV 13.6%). In radical prostatectomy specimens the cancers were mostly 'significant' (92% in main study group and 87% in side-study group). CONCLUSIONS: A randomized screening study for prostate cancer is feasible in Switzerland. A longer follow-up is needed to address within the ERSPC the primary hypothesis (that there will be a reduction in mortality in the active screening arm) and to determine the level of over/under-diagnosis and over/undertreatment in the active screening and control arms, respectively.

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Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer.

Journal Journal of the National Cancer Institute
Year 2003
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Cet article est inclus dans 2 Systematic reviews Systematic reviews (2 references)

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BACKGROUND: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening. METHODS: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs. RESULTS: Mean lead times and rates of overdetection depended on a man's age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48% (range = 44%-55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%-87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected. CONCLUSIONS: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year.

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Tumour features in the control and screening arm of a randomized trial of prostate cancer.

Journal European urology
Year 2006
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OBJECTIVE: To compare tumour characteristics at the time of diagnosis of cancers detected in the screening and control arm at the Rotterdam section of the European Randomized study of Screening for Prostate Cancer. METHODS: Data were retrieved from the Rotterdam section of the ERSPC. Men were randomized to the screening arm (n=21,210) or the control arm (n=21,166). Men randomized to screening were offered PSA testing every 4 years. Through linkage with the cancer registry, men randomized to the control arm were detected. The biopsy Gleason score was determined in 1,591 and 373 patients in the screening and control arm, respectively. TURP, radical prostatectomy (RP) and cystoprostatectomy were evaluated for Gleason score, pathological (p)T stage and tumour volume. RESULTS: More prostate cancers were detected in the screening arm (15.9 vs. 4.2 per 1000 man years, p<0.0001). Clinical stage distribution as well as biopsy and RP Gleason score distribution were significantly less favourable in the control arm. The incidence in man years of advanced disease (i.e. T4/N1/M1) was higher in the screening arm (6.0 per 100,000) as compared to the control arm (4.6 per 100,000). The 5-year PSA progression free survival after RP was 68% in the control arm and 89% in the screening arm (p<0.0001). The proportion of Incidental prostate cancers was 9.3% of all cancers detected in the control arm. CONCLUSIONS: Although the number of men with advanced prostate cancer is slightly higher in the screening arm, the proportion of prostate cancers with favourable features is increased in the screening arm as compared to that in the control arm.

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Le dépistage du cancer de la prostate diminue le risque absolu d'être diagnostiqué à un stade avancé de la prostate - les résultats d'une étude prospective, basée sur la population essai contrôlé randomisé.

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Journal European urology
Year 2007
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Cet article est inclus dans 3 Systematic reviews Systematic reviews (3 references)

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OBJECTIFS: Les essais contrôlés randomisés sont actuellement menées pour déterminer si la mortalité par cancer de la prostate est réduite par une détection précoce à l'utilisation de l'antigène prostatique spécifique (PSA) mesurés dans le sérum. Pour être efficace, un tel programme devrait être en mesure de réduire le nombre absolu des hommes diagnostiqués avec le cancer de la prostate métastatique (pour laquelle aucun remède n'est disponible). L'objectif du présent rapport est d'évaluer si le dépistage du PSA réduit le risque d'être diagnostiqué avec un cancer métastatique de la prostate. MÉTHODES: Une basée sur la population, prospective, randomisée, contrôlée essai de dépistage pour le cancer de la prostate a débuté en 1995 (la branche de Göteborg de l'étude européenne randomisée de dépistage du cancer de la prostate [ERSPC]). Dix mille hommes choisis au hasard, âgés de 50-66 ans ont été invités pour le test PSA biennale, avec 10.000 hommes servant de témoins passifs pour lesquels le diagnostic de cancer de la prostate métastatique a été surveillée en utilisant le registre suédois du cancer. Résultats: Après un suivi de 10 ans, le risque d'être diagnostiqué avec un cancer métastatique de la prostate a diminué de 48,9%, c'est-, passant de 47 cas dans le groupe témoin de 24 cas dans le groupe randomisé à PSA de dépistage ( p = 0,0084). Toutefois, le risque d'être diagnostiqué avec le cancer de la prostate a augmenté de 1,8 fois avec PSA de dépistage. CONCLUSIONS: Biennale de dépistage de l'APS réduit le risque d'être diagnostiqué avec le cancer de la prostate métastatique, la première condition pour la réalisation de la mortalité par cancer a diminué chez les jeunes hommes. Cet avantage présumé est contrebalancé par un risque 1,8 fois plus élevé pour le diagnostic de cancer de la prostate.

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Overall and disease-specific survival of patients with screen-detected prostate cancer in the European randomized study of screening for prostate cancer, section Rotterdam.

Journal European urology
Year 2007
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INTRODUCTION: This report describes survival data of participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, diagnosed with prostate cancer (pCA) during the first round of screening, the prevalence screen. PATIENTS AND METHODS: pCA characteristics from cases diagnosed during the first screening round from December 1993 to March 2000 are shown. During follow-up, data were collected by semiannual patient chart review for the first 5 yr and annually thereafter. The causes of death are scored according to the diagnosis of the treating physician and are not based on the review of the independent causes-of-death committee. Overall and disease-specific survival graphs are shown in Kaplan-Maier projections and compared with expected survival outcomes for males in the same age categories from the Dutch provinces of North Holland and Flevoland. Statistical evaluation was based on Cox regression analysis. RESULTS: During the prevalence screening, 1014 patients were diagnosed with pCA. Median follow up was 55 mo, 126 (12.4%) patients died, 20 (2.0%) of pCA. Overall 5-yr observed and expected disease-specific survival was 97.7% and 82%, respectively. In the multivariate analysis, a Gleason sum of 4+4 or higher (p=0.025) was predictive of pCA death. CONCLUSIONS: The observed survival data are in line with the literature and the expected favorable outcome for a screened population. The proportion of men dying from pCA is still small, and a 10-yr follow-up period for the final evaluation of the ERSPC may be too short.

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Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer.

Journal British journal of cancer
Year 2009
Liens Pubmed DOI PubMed Central

Cet article est inclus dans 2 Systematic reviews Systematic reviews (2 references)

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BACKGROUND: Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated. METHODS: The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100,000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100,000 men and for United Kingdom and United States are compared. RESULTS: Without screening 2378 men per 100,000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to 60,695,000 euro. Overdetection is related to 39% of total costs (23,669,000 euro). Screening until age 75 is relatively most expensive because of the costs of overtreatment. CONCLUSION: Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.

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[Résultats et facteurs de participation à l'étude européenne randomisée de dépistage du cancer de la prostate (ERSPC) avec l'antigène prostatique spécifique: départements français du Tarn et de l'Hérault].

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Journal Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie
Year 2009
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Cet article est inclus dans 4 Systematic reviews Systematic reviews (4 references) 1 Broad synthesis Broad syntheses (1 reference)

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INTRODUCTION: modalités de dépistage de masse reste controversé et a fait de grandes études nécessaires. L'étude européenne randomisée de dépistage du cancer de la prostate (ERSPC) a été lancé en 1994. Huit pays, dont la France, y participent. MÉTHODES: ERSPC est une étude multicentrique, randomisée et a commencé avec le but de déterminer si une réduction de 20% la mortalité par cancer de la prostate peut être réalisé avec PSA de dépistage. Les hommes âgés de 50-74 et de vivre dans le Tarn ou l'Hérault ont été inclus. Après randomisation et exclusion de ceux qui sont morts ou qui a eu un cancer de la prostate ont été invités à participer en donnant leur consentement et a eu un test de l'APS. Dans le cas d'une plus grande ou égale à 3 ng / ml de PSA, une biopsie est recommandée. Les hommes inclus dans le dépistage et le groupe témoin ont été suivies par les registres du cancer. L'objectif était de présenter Résultats du premier tour de la participation française à l'ERSPC, pour déterminer les facteurs de participation et de comparer les cas de cancers détectés entre les deux groupes. RÉSULTATS: La population d'hommes inclus était de 84 781 et ont été randomisés dans le dépistage (n = 42 590) ou témoin (n = 42 191) de groupe. Le taux de participation était de 36,9% dans le Tarn et 24,3% dans l'Hérault. PSA était supérieur ou égal à 3 ng / ml dans 15,4% des cas (n = 1812) et 45,9% des hommes (n = 832) qui ont été biopsiés. L'âge, le PSA précédente réalisée dans les deux années qui ont précédé à l'invitation, d'assurance maladie et département de résidence étaient significativement associés au taux de participation. Incidence cumulée avec quatre ans de suivi était de 2,48% (n = 1053) dans le dépistage et 1,99% (n = 840) dans le groupe témoin, avec un risque relatif (RR) de 1,242. RR correspondant du Tarn et de l'Hérault étaient de 1,37 et 1,20 respectivement. Les paramètres cliniques et les modalités de traitements étaient similaires entre les deux groupes de dépistage et de contrôle (prostatectomie radicale 68% et la radiothérapie 20%). CONCLUSION: Taux de participation au premier tour était modeste. Profil des hommes qui ont participé par rapport aux hommes qui n'ont pas étaient différents. Le groupe de contrôle a probablement été contaminé par le dosage du PSA protocole d'étude à l'extérieur. Conséquences au niveau ERSPC de ce faible taux de participation en dernière analyse, restent à déterminer.

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Risk of dying from prostate cancer in men randomized to screening differences between: Attendees and nonattendees

Auteurs Bergdahl AG , Aus G , Lilja H , Hugosson J
Journal Cancer
Year 2009
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BACKGROUND: Although the true benefits and disadvantages of prostate cancer screening are still not known, the analysis of fatal cases is important for increasing knowledge of the effects of prostate cancer screening on mortality. Who dies from prostate cancer despite participation in a population-based prostate-specific antigen (PSA) screening program? METHODS: From the Goteborg branch of the European Randomized study of Screening for Prostate Cancer, 10,000 men randomly assigned to active PSA-screening every second year formed the basis of the present study. Prostate cancer mortality was attributed to whether the men were attendees in the screening program (attending at least once) or nonattendees. RESULTS: Thirty-nine men died from prostate cancer during the first 13 years. Both overall (34% vs 13 %; P < .0001) and cancer-specific mortality (0.8% vs 0.3 %; P < .005) were found to be significantly higher among nonattendees compared with attendees. Furthermore, the majority of deaths (12 of 18) among screening attendees were in men diagnosed at first screening (prevalent cases). Only 6 deaths (including 3 interval cases) were noted among men complying with the biennial screening program. CONCLUSIONS: Nonattendees in prostate cancer screening constitute a high-risk group for both death from prostate cancer and death from other causes comparable to that described in other cancer screening programs. © 2009 American Cancer Society.

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Réduction de la mortalité par cancer de la prostate par l'antigène prostatique spécifique sur le dépistage ajusté pour la non-participation et la contamination dans l'étude européenne randomisée de dépistage du cancer de la prostate (ERSPC).

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Journal European urology
Year 2009
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CONTEXTE: antigène prostatique spécifique (PSA) pour le dépistage du cancer de la prostate basé sur (PCa) a été montré pour réduire la mortalité spécifique de la prostate de 20% dans une intention à l'écran (ITS) analyse dans un essai randomisé (étude randomisée européenne sur le dépistage du cancer de la prostate [ERSPC]). Cet effet peut être dilué par la non-participation chez les hommes randomisés dans le bras dépistage et la contamination chez les hommes randomisés dans le bras contrôle. OBJECTIF: Évaluer l'ampleur de la réduction de la mortalité spécifique au cancer de la prostate après ajustement pour la non-participation et de la contamination. Schéma, environnement et participants Nous avons analysé la présence de PCa décès au cours d'un suivi moyen de 9 ans à 162.243 hommes de 55 à 69 an de l'âge randomisés dans sept centres participant à l'ERSPC. Centres ont également été regroupés en fonction du type de randomisation (avant ou après consentement éclairé). INTERVENTION: la non-participation a été définie comme nonattending le tour de dépistage initial dans ERSPC. L'estimation de la contamination était basée sur l'utilisation de PSA dans les contrôles dans ERSPC Rotterdam. MESURES: Les risques relatifs (RR) avec des intervalles de confiance à 95% (IC) ont été comparés entre une analyse des STI et des analyses d'ajustement pour la non-participation et de la contamination à l'aide d'une méthode statistique mis au point à cet effet. RÉSULTATS ET LIMITATIONS: Dans l'analyse STI, le risque relatif de décès CaP chez les hommes affectés au groupe d'intervention par rapport au groupe témoin était de 0,80 (IC 95%, 0.68 à 0.96). Ajustement pour non-participation abouti à un RR de 0,73 (IC 95%, 0.58 à 0.93), et l'ajustement supplémentaire pour la contamination en utilisant deux différentes estimations ont conduit à des réductions estimées de 0,69 (IC 95%, 0.51 au 0,92) à 0,71 (IC à 95%, de 0.55 à 0,93), respectivement. Données de contamination ont été obtenues par extrapolation des données dans un seul centre. Aucune hétérogénéité n'a été observée entre les groupes de centres. CONCLUSIONS: Le dépistage du PSA réduit le risque de mourir d'un cancer de la prostate jusqu'à 31% chez les hommes effectivement dépistés. Cet avantage devrait être mis en balance avec un degré de surdiagnostic et de surtraitement inhérente au dépistage du cancer de la prostate.

Primary study

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La mortalité de dépistage et de la prostate-cancer dans une étude randomisée européenne.

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Journal The New England journal of medicine
Year 2009
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CONTEXTE: L'étude européenne randomisée de dépistage du cancer de la prostate a été lancé dans les années 1990 pour évaluer l'effet du dépistage de la prostate-spécifique de l'antigène (APS) sur les taux de mortalité par cancer de la prostate. MÉTHODES: Nous avons identifié 182.000 hommes entre les âges de 50 et 74 ans par le biais des registres dans sept pays européens pour l'inclusion dans notre étude. Les hommes ont été assignés au hasard à un groupe qui a été offert au dépistage de l'APS en moyenne une fois tous les 4 ans ou à un groupe témoin qui n'a pas reçu un tel dépistage. Le noyau du groupe prédéfini d'âge pour cette étude a porté sur 162,243 hommes entre les âges de 55 et 69 ans. Le critère principal était le taux de décès par cancer de la prostate. Suivi de la mortalité a été identique pour les deux groupes d'étude et s'est terminé le Décembre 31, 2006. RÉSULTATS: Dans le groupe de dépistage, 82% des hommes ont accepté au moins une offre de dépistage. Pendant un suivi médian de 9 ans, l'incidence cumulative de cancer de la prostate était de 8,2% dans le groupe dépistage et de 4,8% dans le groupe témoin. Le ratio des taux de décès par cancer de la prostate dans le groupe dépistage, par rapport au groupe témoin, était de 0,80 (intervalle de confiance 95% [IC], 0,65 à 0,98; ajusté P = 0,04). La différence de risque absolu était de 0,71 décès pour 1000 hommes. Cela signifie que les hommes 1410 devrait être dépistés et 48 cas supplémentaires de cancer de la prostate devraient être traités pour prévenir un décès par cancer de la prostate. L'analyse des hommes qui ont été effectivement dépistés lors du premier tour (à l'exclusion des sujets non-conformité avec) a fourni un rapport des taux de décès par cancer de la prostate de 0,73 (IC à 95%, 0,56 à 0,90). CONCLUSIONS: PSA-dépistage réduit le taux de décès par cancer de la prostate de 20%, mais a été associée à un risque élevé de surdiagnostic. (Mise à jour nombre Controlled Trials, ISRCTN49127736.)

Primary study

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False-positive screening results in the Finnish prostate cancer screening trial

Journal British journal of cancer
Year 2010
Liens Pubmed DOI PubMed Central
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Background:There is evidence that prostate cancer (PC) screening with prostate-specific antigen (PSA) serum test decreases PC mortality, but screening has adverse effects, such as a high false-positive (FP) rate. We investigated the proportion of FPs in a population-based randomised screening trial in Finland.Methods:Finland is the largest centre in the European Randomized Study of Screening for Prostate Cancer. We have completed three screening rounds with a 4-year screening interval (mean follow-up time 9.2 years) using a PSA cutoff level of 4.0 ng ml 1; in addition, men with PSA 3.0-3.9 and a positive auxiliary test were referred. An FP result was defined as a positive screening result without cancer in biopsy within 1 year from the screening test.Results:The proportion of FP screening results varied from 3.3 to 12.1% per round. Of the screened men, 12.5% had at least one FP during three rounds. The risk of next-round PC following an FP result was 12.3-19.7 vs 1.4-3.7% following a screen-negative result (depending on the screening round), risk ratio 3.6-9.9. More than half of the men with one FP result had another one at a subsequent screen. Men with an FP result were 1.5 to 2.0 times more likely to not participate in subsequent rounds compared with men with a normal screening result (21.6-29.6 vs 14.0-16.7%).Conclusion:An FP result is a common adverse effect of PC screening and affects at least every eighth man screened repeatedly, even when using a relatively high cutoff level. False-positive men constitute a special group that receives unnecessary interventions but may harbour missed cancers. New strategies are needed for risk stratification in PC screening to minimise the proportion of FP men. © 2010 Cancer Research UK.

Primary study

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Résultats de mortalité de la Göteborg randomisée basée sur la population essai de dépistage de la prostate et le cancer.

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Journal The lancet oncology
Year 2010
Liens Pubmed DOI PubMed Central
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CONTEXTE: Le cancer de la prostate est l'une des causes principales de décès dus aux maladies malignes chez les hommes dans le monde développé. Une stratégie visant à diminuer le risque de décès par cette maladie est le dépistage de la prostate-specific antigen (PSA), mais, dans la mesure du bénéfice et des dommages avec un tel dépistage est en cours de débat permanent. MÉTHODES: En Décembre 1994, 20.000 hommes nés entre 1930 et 1944, choisies au hasard dans le registre de la population, ont été randomisés par ordinateur dans un rapport 1:1 soit à un groupe de dépistage invité pour PSA de tester tous les 2 ans (n ​​= 10.000) ou à un groupe témoin non invité (n = 10.000). Les hommes du groupe de dépistage ont été invités à la limite d'âge supérieure (médiane 69, plage de 67-71 ans) et seuls les hommes ayant des concentrations de PSA soulevées ont été offerts des tests supplémentaires tels que le toucher rectal et des biopsies de la prostate. Le critère principal était la mortalité par cancer de la prostate spécifique, analysé selon le principe de l'intention à l'écran. L'étude est en cours, avec des hommes qui n'ont pas atteint la limite d'âge supérieure pour les invités test de l'APS. Ce rapport est le premier projet sur le cancer de la prostate cumulatif d'incidence et de mortalité calculés jusqu'à 31 décembre 2008. Cette étude est enregistré comme un essai international randomisé contrôlé standard ISRCTN54449243. RÉSULTATS: Dans chaque groupe, 48 hommes ont été exclus de l'analyse en raison du décès ou de l'émigration avant la date de randomisation, ou cancer de la prostate répandu. Chez les hommes randomisés de dépistage, 7578 (76%) de 9952 ont participé à au moins une fois. Pendant un suivi médian de 14 ans, 1138 hommes dans le groupe dépistage et 718 dans le groupe témoin ont été diagnostiqués avec le cancer de la prostate, résultant dans un cumulatif de la prostate-cancer incidence de 12,7% dans le groupe dépistage et de 8,2% dans le groupe témoin (hazard ratio 1,64, IC 95% 1.50 à 1.80, p <0,0001). La réduction du risque absolu cumulatif de décès par cancer de la prostate à 14 ans était de 0,40% (IC à 95% de 0.17 à 0.64), de 0,90% dans le groupe témoin à 0,50% dans le groupe dépistage. Le ratio des taux de décès par cancer de la prostate était de 0,56 (IC à 95% de 0,39 à 0,82, p = 0,002) dans le dépistage par rapport au groupe témoin. Le ratio des taux de décès par cancer de la prostate pour les participants par rapport au groupe témoin était de 0,44 (IC à 95% de 0,28 à 0,68, p = 0,0002). Globalement, les hommes 293 (95% CI 177-799) avait besoin d'être invité pour le dépistage et 12 d'être diagnostiqués pour prévenir un décès par cancer de la prostate. Interprétation: Cette étude montre que la mortalité par cancer de la prostate a été réduit presque de moitié plus de 14 ans. Cependant, le risque de sur-diagnostic est importante et le nombre nécessaire à traiter est au moins aussi élevé que dans les programmes de dépistage du cancer du sein. L'avantage de la prostate de dépistage du cancer se compare favorablement à d'autres programmes de dépistage du cancer. FINANCEMENT: La Société du cancer suédois, le Conseil de recherche suédois, et le National Cancer Institute.

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Unclassified

The Göteborg randomised population based prostate cancer screening trial

Registry of Trials ISRCTN registry
Year 2010
Liens DOI isrctn.com
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Prostate specific antigen (PSA) screening decreases prostate cancer mortality by 40% after 15 years.

Primary study

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The effect of study arm on prostate cancer treatment in the large screening trial ERSPC

Journal International journal of cancer
Year 2010
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Prostate cancer (PC) mortality is the most valid end-point in screening trials, but could be influenced by the choice of initial treatment if treatment has an effect on mortality. In this study, PC treatment was compared between the screening and control arms in a screening trial. Data were collected from the European Randomized Study of Screening for Prostate Cancer (ERSPC). The characteristics and initial treatment of PC cases detected in the screening and the control arm were compared. Polytomous logistic regression analysis was used to assess the influence of study arm on treatment, adjusting for potential confounders and with statistical imputation of missing values. A total of 8,389 PC cases were detected, 5,422 in the screening arm and 3,145 in the control arm. Polytomous regression showed that trial arm was associated with treatment choice after correction for missing values, especially in men with high-risk PC. A control subject with high-risk PC was more likely than a screen subject to receive radiotherapy (OR: 1.43, 95% CI: 1.01-2.05, p = 0.047), expectant management (OR: 2.92, 95% CI: 1.33-6.42, p = 0.007) or hormonal treatment (OR: 1.77, 95% CI: 1.07-2.94, p = 0.026) instead of radical prostatectomy. However, trial arm had only a minor role in treatment choice compared to other variables. In conclusion, a small effect of trial arm on treatment choice was seen, particularly in men with high-risk PC. Therefore, differences in treatment between arms are unlikely to play a major role in the interpretation of the results of the ERSPC. © 2009 UICC.

Primary study

Unclassified

Results of the three rounds of the Finnish prostate cancer screening trial - The incidence of advanced cancer is decreased by screening

Journal International journal of cancer. Journal international du cancer
Year 2010
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Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12-year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate-specific antigen test (cut-off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow-up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen-detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person-years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4-1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6-0.8) and the difference emerges after 5-6 years of follow-up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5-1.7). The results from our large population-based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low-grade PCs due to overdiagnosis. © 2010 UICC.

Primary study

Unclassified

False-positive screening results in the European randomized study of screening for prostate cancer.

Journal European journal of cancer (Oxford, England : 1990)
Year 2011
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Abstract: BACKGROUND: Screening for prostate cancer (PC) with prostate-specific antigen (PSA) has been shown to decrease mortality, but has adverse effects, such as false-positive (FP) screening results. We describe the frequency of FP results and assess their relation to subsequent screening attendance, test results and prostate cancer risk in a large randomized trial. Materials and methods: We included data from five centres of the European Randomized Study of Screening for Prostate Cancer, altogether over 61,000 screened men. Men were screened with PSA test at a 2–7year interval depending on the centre; PSA cut-off was 3.0–4.0ng/ml. A positive screen with no histologically confirmed PC in biopsy within 1year was defined as an FP result. RESULTS: Of the 61,604 men who were screened at least once, 17.8% had one or more FP result(s). Almost 20% of men who participated at all screening rounds had one or more FP result(s). More than half of the men with an FP result had another FP if screened again. Men with FP results had a fourfold risk of PC at subsequent screen (depending on the round, 10.0% versus 2.6–2.7% of men with negative screen, risk ratio 3.8–3.9). The PCs following an FP result were in 92.8% of cases localised and low-grade versus 90.4% following a screen-negative result. CONCLUSIONS: Our results show that FP results are common adverse effects in PC screening, as they affect at least one in six screened men. False-positive men are more prone to be diagnosed with PC but are also likely to have consistently high PSA levels.

Primary study

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No excess mortality after prostate biopsy: results from the European Randomized Study of Screening for Prostate Cancer.

Journal BJU international
Year 2011
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OBJECTIVE: • To assess possible excess mortality associated with prostate biopsy among screening participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC). PATIENTS AND METHODS: • From three centres in the ERSPC (Finland, The Netherlands and Sweden) 50,194 screened men aged 50.2-78.4 years were prospectively followed. A cohort of 12,959 first-time screening-positive men (i.e. with biopsy indication) was compared with another cohort of 37,235 first-time screening-negative men. • Overall mortality rates (i.e. other cause than prostate cancer mortality) were calculated and the 120-day and 1-year cumulative mortality were calculated by the Kaplan-Meier method, with a log-rank test for statistical significance. • Incidence rate ratios (RR) and statistical significance were evaluated using Poisson regression analyses, adjusting for age, total PSA level, screening centre and whether a biopsy indication was present, or whether a biopsy was actually performed or not. RESULTS: • There was no statistically significant difference in cumulative 120-day other cause mortality between the two groups of men: 0.24% (95% CI, 0.17-0.34) for screening-positive men vs 0.24% (95% CI, 0.20-0.30) for screening-negative men (P= 0.96). This implied no excess mortality for screening-positive men. • Screening-positive men who were not biopsied (n= 1238) had a more than fourfold risk of other cause mortality during the first 120 days compared to screening-negative men: RR, 4.52 (95% CI, 2.63-7.74) (P < 0.001), adjusted for age, whereas men who were actually biopsied (n= 11,721) had half the risk: RR, 0.41 (95% CI, 0.23-0.73) (P= 0.002), adjusted for age. • Only 14/31 (45%) of the screening-positive men who died within 120 days were biopsied and none died as an obvious complication to the biopsy. CONCLUSION: • Prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare.

Primary study

Unclassified

Identifying and characterizing "escapes"-men who develop metastases or die from prostate cancer despite screening (ERSPC, section Rotterdam).

Journal International journal of cancer. Journal international du cancer
Year 2011
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We aim to identify and characterize "escapes," men who developed metastasis and/or died from prostate cancer (PCa) despite screening, in the framework of the novel international ESCAPE-project. With this knowledge, the ultimate goal is to improve screening strategy. In this article, we focus on the study cohort of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. In all, 21,210 men were randomized to the screening arm of whom 19,950 were actually screened. The screening interval was 4 years. Men with prostate-specific antigen ≥3.0 ng/ml were recommended to undergo lateralized sextant prostate biopsy. The follow-up was complete until January 1, 2009. Of 19,950 screened men, 2,317 were diagnosed with PCa. Of these cancers 1,946 were detected in a screening round and 371 during an interval. The median follow-up was 11.1 years for the whole cohort and 7.3 years for men diagnosed with PCa. In total, we identified 168 escapes among 2,317 cancers (7.3%) within our screening cohort of 19,950 men (0.8%). More than half of these escapes were found in the initial screening round (94 of 168). Possible mechanisms behind escaping are nonattending, inadequate screening tests, the relative long screening interval, the age cut-off at 75 years, and undertreatment. International cooperation is crucial to compare the escapes of our cohort with other study groups participating in the ESCAPE-project which have different, more aggressive screening strategies. Subsequently, we can achieve improvements of the current screening algorithm, which hopefully will further decrease PCa-specific mortality without increasing overdiagnosis and overtreatment.

Primary study

Unclassified

Comparison of risk calculators from the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer in a contemporary Canadian cohort.

Journal BJU international
Year 2011
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OBJECTIVE: •To compare the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC-RC) in a single-institution Canadian cohort. PATIENTS AND METHODS: •At Princess Margaret Hospital, 982 consecutive patients with PCPT-RC and ERSPC-RC covariables were prospectively catalogued before prostate biopsy for suspicion of prostate cancer (PCa). •Receiver-operating characteristic (ROC) curves were generated for each calculator and prostate-specific antigen (PSA). •Comparisons by area under the curve (AUC) and calibration plots were performed. •Predictors of PCa were identified by univariable and multivariable logistic regression. RESULTS: •PCa was detected in 46% and high-grade (HG) PCa (Gleason ≥4) in 23% of subjects with a median PSA level of 6.02 ng/mL. • Multivariable analysis identified transrectal ultrasonography nodule, prostate volume and PSA as the most important predictors of PCa and HG PCa. •ROC curve analysis showed that the ERSPC-RC (AUC = 0.71) outperformed the PCPT-RC (AUC = 0.63) and PSA (AUC = 0.55), for PCa prediction, P < 0.001. •The PCPT-RC was better calibrated in the higher prediction range (40-100%) than the ERSPC-RC, whereas the ERSPC-RC had better calibration and avoided more biopsies in the lower risk range (0-30%). •Discrimination of the ERSPC-RC continued to be superior to the PCPT-RC when the cohort was stratified by different clinical variables. CONCLUSIONS: •The ERSPC-RC had better discrimination for predicting PCa compared to the PCPT-RC in this Canadian cohort. •Calibration would need to be improved to allow routine use of the ERSPC-RC in Canadian practice.

Primary study

Unclassified

Disease-specific survival of men with prostate cancer detected during the screening interval: results of the European randomized study of screening for prostate cancer-Rotterdam after 11 years of follow-up.

Journal European urology
Year 2011
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BACKGROUND: In a screening program, interval cancers are cancers diagnosed between two screening visits. OBJECTIVE: To assess the disease-specific survival (DSS) of men with prostate cancer (PCa) detected during the screening interval. DESIGN, SETTING, AND PARTICIPANTS: Within the European Randomized Study of Screening for Prostate Cancer section Rotterdam, 42 376 men identified from population registries (55-74 yr of age) were randomized to a screening or control arm. The median follow-up was 11 yr. INTERVENTION: Men with prostate-specific antigen ≥ 3.0 ng/ml were recommended to undergo lateralized sextant biopsy. The screening interval was 4 yr. MEASUREMENTS: The disease-specific mortality of men with interval cancers was compared with that of men with PCa in the control arm; the secondary end point was overall mortality. An independent committee determined the causes of death. RESULTS AND LIMITATIONS: In the screening arm, 139 men were diagnosed with interval cancer of whom 8 died of the disease. In the control arm, the corresponding numbers were 1149 and 128, respectively. When comparing men with interval cancer to men with PCa in the control arm, no statistically significant difference in disease-specific mortality (hazard ratio [HR]:1.12; 95% confidence interval [CI], 0.53-2.36; p = 0.77) and overall mortality (HR: 0.98; 95% CI, 0.68-1.38; p = 0.90) was found, adjusted for age, prognostic factors, and treatment modality. The follow-up is too limited to address the difference in DSS stratified for screening interval. CONCLUSIONS: In the setting of population-based PCa screening at 4-yr intervals, the DSS of men with interval cancer seems to be similar to that of men with PCa in the control arm. Given that interval cancers contribute significantly to PCa mortality, further benefit in DSS in the screening arm may be achieved by decreasing the occurrence of interval cancer. However, the balance between mortality reduction and overdiagnosis should be preserved. TRIAL REGISTRATION: ISRCTN49127736.

Primary study

Unclassified

[Mortality due to prostate cancer in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Results after a 15-year follow-up].

Journal Actas urologicas espanolas
Year 2012
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OBJECTIVE: To address if prostate cancer (PCa) screening decreases PCa mortality in the asymptomatic population, within the setting of the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC). MATERIAL AND METHODS: From 1996 to 1999, 4,278 men aged 45-70 years were recruited and randomized to the screening arm (PSA every 4 years, prostate biopsy when PSA ≥3 ng/ml) and control arm (no tests). Dates and causes of death were collected on an annual basis. A Kaplan-Meier analysis was used to calculate overall and cancer-specific survival. RESULTS: A total of 2,416 men were recruited in the screening arm and 1,862 in the control arm. Mean age was 57.8 years, median follow-up was 13.3 years. At the end of the follow-up period, 427 deaths (9 from PCa) were observed. Survival analysis did not show any difference between the study arms with respect to overall and cancer-specific survival (p=0.939 and p=0.544 respectively). Most relevant causes of death were malignant tumors (52.9%), cardiovascular disease (17.3%) and respiratory (8.9%). Only 2.1% of deaths (0.2% of all recruited men) were due to PCa (2.5% screening, 1.6% control). CONCLUSIONS: The Spanish arm of ERSPC failed to reproduce the long-term results shown in the whole study. No differences in mortality (overall or cancer-specific) were observed after 15 years of follow-up. PCa mortality was infrequent (less than 1%). These results suggest limited yield of PCa screening in our setting.

Primary study

Unclassified

Prostate-cancer mortality at 11 years of follow-up.

Journal The New England journal of medicine
Year 2012
Liens Pubmed DOI PubMed Central
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<b>BACKGROUND: </b>Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up.<b>METHODS: </b>The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer.<b>RESULTS: </b>After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality.<b>CONCLUSIONS: </b>Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

Primary study

Unclassified

Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC).

Journal European urology
Year 2012
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BACKGROUND: Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal. OBJECTIVE: To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial. DESIGN, SETTING, AND PARTICIPANTS: Data were available for 76,813 men aged 55-69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up. INTERVENTION: Regular screening based on serum PSA measurements was offered to 36270 men randomized to the screening arm, while no screening was provided to the 40543 men in the control arm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease. RESULTS AND LIMITATIONS: After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p<0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60-0.82; p=0.001) in the intention-to-screen analysis and a 42% (p=0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41-0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up. CONCLUSIONS: PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736.

Primary study

Unclassified

Effects of prostate cancer screening on health-related quality of life: results of the Finnish arm of the European randomized screening trial (ERSPC).

Journal Acta oncologica (Stockholm, Sweden)
Year 2013
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BACKGROUND: As prostate cancer (PC) mortality reduction results are not unequivocal, a special emphasis has to be put on other aspects of the prostate-specific antigen (PSA) screening, including effects on quality of life. In the present study we describe the short-term effects of various phases of PC screening on health-related quality of life (HRQL). MATERIAL AND METHODS: The study participants were randomized into the screening arm within the Finnish component of the European Randomized Study on Screening for Prostate Cancer (ERSPC). The RAND 36-Item Health Survey on HRQL and questionnaires on sociodemographic and behavioral factors were delivered to participants at various phases of the first screening round: 1) 500 participants at invitation; 2) 500 after screening; 3) 500 after obtaining the PSA result; 4) to 300 participants after undergoing digital rectal examination (DRE) (but prior to being informed of its result); and 5) approximately 300 after prostate biopsy. At each stage, a new sample of participants was recruited. RESULTS: Response rates were 59% at invitation, 77% after PSA blood test, 54% after PSA result and 69% after DRE. The men recruited at each stage were comparable in respect to socioeconomic variables. The HRQL scores in RAND-36 subscales showed little variation in the different phases of the screening process. Compared with the previous phase, the social function score was slightly lower after obtaining the PSA result than after blood test, the emotional role score lower after DRE than after PSA result and the pain-related score lower after DRE than after TRUS and biopsy. The screening participants were comparable to the general population as their HRQL scores were similar to an age-stratified general Finnish male population. CONCLUSION: Short-term HRQL effects of prostate cancer screening appear minor and transient.

Primary study

Unclassified

Prostate cancer mortality in the Finnish randomized screening trial.

Journal Journal of the National Cancer Institute
Year 2013
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BACKGROUND: Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality. METHODS: A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided. RESULTS: PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms. CONCLUSIONS: At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.

Primary study

Unclassified

Screening for prostate cancer: results of the Rotterdam section of the European randomized study of screening for prostate cancer.

Journal European urology
Year 2013
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BACKGROUND: Evidence from randomized trials on the effects of screening for prostate cancer (PCa) on disease-specific mortality accumulates slowly with increasing follow-up. OBJECTIVE: To assess data on PCa-specific mortality in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial with randomization after signed, written informed consent (efficacy trial). In the period 1993-1999, a total of 42 376 men aged 54-74 yr were randomized to a screening arm (S-arm) (n = 21 210 with screening every 4 yr, applying a total prostate-specific antigen [PSA] level cut-off ≥ 3.0 ng/ml as biopsy indication) or a control arm (C-arm) (n = 21 166; no intervention). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Number of PCas detected per arm depicted by predefined time periods and prognostic groups. PCa-specific mortality analyses using Poisson regression in age group 55-74 yr at randomization and separately in the predefined age group of 55-69 yr. RESULTS AND LIMITATIONS: After a median follow-up of 12.8 yr, 19 765 men (94.2%) were screened at least once and 2674 PCas were detected (of which 561 [21.0%] were interval PCas). In the C-arm, 1430 PCas were detected, resulting in an excess incidence of 59 PCas per 1000 men randomized (61 PCas per 1000 in age group 55-69 yr). Thirty-two percent of all men randomized have died. PCa-specific mortality relative-risk (RR) reductions of 20.0% overall (age: 55-74 yr; p = 0.042) and 31.6% (age: 55-69 yr; p = 0.004) were found. A 14.1% increase was found in men aged 70-74 yr (not statistically significant). Absolute PCa mortality was 1.8 per 1000 men randomized (2.6 per 1000 men randomized in age group 55-69 yr). The number needed to invite and number needed to manage were 565 and 33, respectively, for age group 55-74 yr, and 392 and 24, respectively, for age group 65-69 yr. Given the slow natural history of the disease, follow-up might be too short. CONCLUSIONS: Systematic PSA-based screening reduced PCa-specific mortality by 32% in the age range of 55-69 yr. The roughly twofold higher incidence in the S-arm underlines the importance of tools to better identify those men who would benefit from screening.

Primary study

Unclassified

Incidence of prostate cancer after termination of screening in a population-based randomised screening trial.

Journal European urology
Year 2013
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BACKGROUND: In a previous publication from the Göteborg randomised screening trial from 2010, biennial prostate-specific antigen (PSA) screening for men ≤69 yr of age was shown to lower prostate cancer (PCa) mortality by 44%. The evidence of the optimal age to stop screening, however, is limited. OBJECTIVE: To examine the risk of PCa after the discontinuation of screening. DESIGN, SETTING, AND PARTICIPANTS: In December 1994, 20 000 men in Göteborg, Sweden, between the ages of 50 and 65 yr were randomised to a screening arm (invited biennially to PSA testing) and a control arm (not invited). At the upper age limit (average: 69 yr), a total of 13 423 men (6449 and 6974 in the screening and control arms, respectively) were still alive without PCa. The incidence of PCa hereafter was established by matching with the Western Swedish Cancer Register. Participants were followed until a diagnosis of PCa, death, or final follow-up on June 30, 2012, or for a maximum of 12 yr after the last invitation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rates and disease-free survival were calculated with life table models and Kaplan-Meier estimates. A competing risk model was also applied. RESULTS AND LIMITATIONS: Postscreening, 173 cases of PCa were diagnosed in the screening arm (median follow-up: 4.8 yr) and 371 in the control arm (median follow-up: 4.9 yr). Up to 9 yr postscreening, all risk groups were more commonly diagnosed in the control arm, but after 9 yr the rates in the screening arm caught up, other than those for the low-risk group. PCa mortality also caught up after 9 yr. CONCLUSIONS: Nine years after the termination of PSA testing, the incidence of potentially lethal cancers equals that of nonscreened men. Considering the high PCa mortality rate in men >80 yr of age, a general age of 70 yr to discontinue screening might be too low. Instead, a flexible age to discontinue based on individual risk stratification should be recommended.

Primary study

Unclassified

Excess all-cause mortality in the evaluation of a screening trial to account for selective participation.

Journal Journal of medical screening
Year 2013
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OBJECTIVE: In addition to disease-specific mortality, a randomized controlled cancer screening trial may be evaluated in terms of excess mortality, in which case no patient-specific information on causes of death is needed. We studied the effect of not accounting for attendance on the calculated excess mortality in a prostate cancer screening trial. METHODS: The numerator of the excess mortality rate related to prostate cancer diagnoses in each study arm equals the excess number of deaths observed in the cancer patients. The estimation of the expected number of deaths in the absence of the prostate cancer diagnoses has to account for the self-selection of those participating in the trial, particularly if the proportion of non-participants is substantial. SETTING: The European prostate cancer screening trial (ERSPC). RESULTS: In the screening arm, non-attendees had roughly twice the mortality rate of attendees. Approximately twice as many cancers were detected in the screening arm compared with the control arm, primarily in attendees. Unless attendance is properly accounted for, the expected mortality of prostate cancer patients in the screening arm is overestimated by 0.9-3.6 deaths per 1000 person-years. CONCLUSIONS: Attendees have a lower all-cause mortality rate (are healthier) and a higher probability of a prostate cancer diagnosis than non-attendees and the men randomized to the control arm. If attendance is not accounted for, the excess mortality and the between-arm excess mortality rate ratio are underestimated and screening is considered more effective than it actually is. These effects may be sizeable, notably if non-attendance is common. Correcting for attendance status is important in the calculation of the excess mortality rate in prostate cancer patients that can be used in conjunction with a disease-specific mortality analysis in a randomized controlled cancer screening trial.

Primary study

Unclassified

Impacts of a population-based prostate cancer screening programme on excess total mortality rates in men with prostate cancer: a randomized controlled trial.

Journal Journal of medical screening
Year 2013
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OBJECTIVES: To assess the effect of screening in terms of excess mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). METHODS: A total of 141,578 men aged 55–69 were randomized to systematic screening or usual care in ERSPC sections in Finland, Italy, the Netherlands and Sweden. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC)patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a diagnosis with PC adjusted for study centre,study arm and study attendance. The excess mortality rates were compared between the two study arms. RESULTS: The PC incidence was 9.25 per 1000 person-years in the intervention arm and 5.49 per 1000 person-years in the control arm, relative risk (RR) 1.69 (95% confidence interval [CI]1.62–1.76). The excess mortality among men with PC was 0.29 per 1000 person-years in the intervention arm and 0.37 per 1000 person-years in the control arm; the RR for excess mortality was 0.77 (95% CI 0.55–1.08). The absolute risk reduction in the excess mortality was 0.08 per 1000 person-years. The overall mortality was not significantly different between the intervention and the control arms of the study: RR 0.99 (95% CI 0.96–1.01). CONCLUSIONS: Although the reduction in excess mortality was not statistically significant, the between arm reduction in excess mortality rate was in line with the previously reported 20% reduction in the disease-specific mortality. This finding indicates that the reduction in PC mortality in the ERSPC trial cannot be due to a bias in cause of death adjudication.

Primary study

Unclassified

Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.

Journal Lancet (London, England)
Year 2014
Liens Pubmed DOI PubMed Central
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BACKGROUND: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. METHODS: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. FINDINGS: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88). INTERPRETATION: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. FUNDING: Each centre had its own funding responsibility.

Primary study

Unclassified

A different method of evaluation of the ERSPC trial confirms that prostate-specific antigen testing has a significant impact on prostate cancer mortality.

Journal European urology
Year 2014
Liens Pubmed DOI PubMed Central
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The advantages and disadvantages of two different methods of analyzing the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with respect to the effect of prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality (ie, disease-specific mortality analysis and excess mortality analysis) are discussed in depth. The traditional disease-specific mortality is the best end point, but it could be biased by misclassification of causes of death, and it does not take into account the possible effect of the screening process on other causes of death. Excess mortality analysis overcomes these problems, but the results could be biased if the expected mortality is not corrected for attendance status. Both methods, when applied to the ERSPC trials, demonstrate that no increase in non-PCa mortality occurred in the screening group and confirm that PSA screening decreases PCa mortality.

Primary study

Unclassified

Prostate cancer incidence and mortality in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

Journal Prostate cancer and prostatic diseases
Year 2014
Liens Pubmed DOI
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BACKGROUND: To present the long-term results of a prostate cancer (PC) screening trial conducted in a Mediterranean setting. METHODS: A total of 4276 men aged 45-70 years were randomized to screening arm (PSA test performed) and control arm (no tests). Transrectal ultrasonography-guided sextant prostate biopsy was conducted when PSA > or = 3 ng ml(-1). Date and cause of death were retrieved from death certificates. PC incidence, and disease-specific and overall mortality curves were plotted and comparison between arms was made. Analysis of causes of death was also performed. RESULTS: Median age at randomization was 57.0 years. Median follow-up time was 15.2 years. A total of 241 men were diagnosed with PC, 161 (6.7%) in the screening arm and 80 (4.3%) in the control arm (P<0.01). Eventually, 554 men (13%) died. No difference in all-cause mortality was found between arms (P=0.34). Only 10 men (10/4276, 0.23%) died from PC, no differences between arms (P=0.67). Overall, the main causes of death were malignancy (54.2%), cardiovascular (17.9%) and respiratory (9.2%) diseases. Main cancer causes of death were lung and bronchus cancer (37.2%), colorectum (15.0%) and stomach (9.0%) cancer. PC only accounted for 3.0% of all malignant causes of death (ranked 10th). CONCLUSIONS: Our study failed to demonstrate benefits of PC screening in terms of all-cause and PC-specific mortality after a median follow-up of 15 years. The limited sample size and the low long-term PC mortality observed in our setting were probably the most important factors to explain these results.

Primary study

Unclassified

Prostate-specific antigen-based prostate cancer screening: reduction of prostate cancer mortality after correction for nonattendance and contamination in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.

Journal European urology
Year 2014
Liens Pubmed DOI
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BACKGROUND: Large randomized screening trials provide an estimation of the effect of screening at a population-based level. The effect of screening for individuals, however, is diluted by nonattendance and contamination in the trial arms. OBJECTIVE: To determine the prostate cancer (PCa) mortality reduction from screening after adjustment for nonattendance and contamination. DESIGN, SETTING, AND PARTICIPANTS: A total of 34,833 men in the core age group, 55-69 yr, were randomized to a screening or control arm in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA) testing was offered to all men in the screening arm at 4-yr intervals. A prostate biopsy was offered to men with an elevated PSA. The primary end point was PCa-specific mortality. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Nonattendance was defined as nonparticipation in the screening arm. Contamination in the control arm was defined as receiving asymptomatic PSA testing or a prostate biopsy in the absence of symptoms. Relative risks (RRs) were calculated with an intention to screen (ITS) analysis and after correction for nonattendance and contamination using a method that preserves the benefits obtained by randomization. RESULTS AND LIMITATIONS: The ITS analysis resulted in an RR of 0.68 (95% confidence interval [CI], 0.53-0.89) in favor of screening at a median follow-up of 13 yr. Correction for both nonattendance and contamination resulted in an RR of 0.49 (95% CI, 0.27-0.87) in favor of screening. CONCLUSIONS: PCa screening as conducted in the Rotterdam section of the ERSPC can reduce the risk of dying from PCa up to 51% for an individual man choosing to be screened repeatedly compared with a man who was not screened. This benefit of screening should be balanced against the harms of overdiagnosis and subsequent overtreatment. TRIAL REGISTRATION: ISRCTN49127736.

Primary study

Unclassified

Prostate cancer risk assessment tools in an unscreened population.

Journal World journal of urology
Year 2015
Liens Pubmed DOI
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OBJECTIVE: To compare the prostate cancer prevention trial risk calculator (PCPT-RC) and European randomized study of screening for prostate cancer risk calculator (ERSPC-RC) in a unique unscreened population from the West of Ireland. PATIENTS AND METHODS: Data was prospectively recorded for all 556 consecutive men who underwent prostate biopsy at our institution as part of the Rapid Access Prostate Assessment Clinic program in Ireland. The estimated probabilities of detecting prostate cancer and high-grade disease were calculated using the PCPT and ERSPC risk calculators. For each calculator the discriminative ability, calibration and clinical utility was assessed. RESULTS: Prostate cancer was detected in 49% and high-grade prostate cancer in 34% of men. Receiver operating characteristic curve analysis demonstrated that the PCPT-RCs outperformed the ERSPC-RCs for the prediction of prostate cancer areas underneath the ROC curve (AUC 0.628 vs. 0.588, p = 0.0034) and for the prediction of high-grade prostate cancer (AUC 0.792 vs. 0.690, p = 0.0029). Both risk calculators generally over-predicted the risk of prostate cancer and high-grade disease across a wide range of predicted probabilities. Decision curve analysis suggested greater net benefit using the PCPT-RCs in this population. CONCLUSIONS: Multivariable nomograms can further aid patient counselling for early prostate cancer detection. In unscreened men from Western Ireland, the PCPT-RCs provided better discrimination for overall prostate cancer and high-grade disease compared to the ERSPC-RC. However, both tools overpredicted the risk of cancer detection on biopsy, and it is possible that a different set of predictive variables may be more useful in this population.

Primary study

Unclassified

Opportunistic testing versus organized prostate-specific antigen screening: outcome after 18 years in the Göteborg randomized population-based prostate cancer screening trial.

Journal European urology
Year 2015
Liens Pubmed DOI
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BACKGROUND: It has been shown that organized screening decreases prostate cancer (PC) mortality, but the effect of opportunistic screening is largely unknown. OBJECTIVE: To compare the ability to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening. DESIGN, SETTING, AND PARTICIPANTS: The Göteborg screening study invited 10 000 randomly selected men for prostate-specific antigen (PSA) testing every 2 yr since 1995, with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml. The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing. Both groups were followed until December 31, 2012. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Observed cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method. Using historical data from 1990-1994 (pre-PSA era), we calculated expected PC incidence and mortality rates in the absence of any PSA testing. The number needed to invite (NNI) and the number needed to diagnose (NND) were calculated by comparing the expected versus observed incidence and mortality rates. RESULTS AND LIMITATIONS: At 18 yr, 1396 men were diagnosed with PC and 79 men died of PC in the screening group, compared to 962 and 122, respectively, in the control group. In the screening group, the observed cumulative PC incidence/mortality was 16%/0.98% compared to expected values of 6.8%/1.7%. The corresponding values for the control group were 11%/1.5% and 6.9%/1.7%. Organized screening was associated with an absolute PC-specific mortality reduction of 0.72% (95% confidence interval [CI] 0.50-0.94%) and relative risk reduction of 42% (95% CI 28-54%). There was an absolute reduction in PC deaths of 0.20% (95% CI -0.06% to 0.47%) and a relative risk reduction of 12% (95% CI -5 to 26%) associated with opportunistic PSA testing. NNI and NND were 139 (95% CI 107-200) and 13 for organized biennial screening and 493 (95% CI 213- -1563) and 23 for opportunistic screening. The extent of opportunistic screening could not be measured; incidence trends were used as a proxy. CONCLUSIONS: Organized screening reduces PC mortality but is associated with overdiagnosis. Opportunistic PSA testing had little if any effect on PC mortality and resulted in more overdiagnosis, with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program. PATIENT SUMMARY: Prostate-specific antigen (PSA) screening within the framework of an organized program seems more effective than unorganized screening.

Primary study

Unclassified

Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer.

Journal European urology
Year 2015
Liens Pubmed DOI PubMed Central
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BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality. DESIGN, SETTING, AND PARTICIPANTS: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis. RESULTS AND LIMITATIONS: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller. CONCLUSIONS: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr. PATIENT SUMMARY: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer.

Primary study

Unclassified

Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary European cohort.

Journal BJU international
Year 2016
Liens Pubmed DOI
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OBJECTIVES: To externally validate and compare the two novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC)-prostate cancer risk calculator (RC) and Prostate Cancer Prevention Trial (PCPT)-RC. PATIENTS AND METHODS: All men who underwent a transrectal prostate biopsy in a European tertiary care centre between 2004 and 2012 were retrospectively identified. The probability of detecting prostate cancer and significant cancer (Gleason score ≥7) was calculated for each man using the novel versions of the ERSPC-RC (DRE-based version 3/4) and the PCPT-RC (version 2.0) and compared with biopsy results. Calibration and discrimination were assessed using the calibration slope method and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, decision curve analyses were performed. RESULTS: Of 1 996 men, 483 (24%) were diagnosed with prostate cancer and 226 (11%) with significant prostate cancer. Calibration of the two RCs was comparable, although the PCPT-RC was slightly superior in the higher risk prediction range for any and significant prostate cancer. Discrimination of the ERSPC- and PCPT-RC was comparable for any prostate cancer (AUCs 0.65 vs 0.66), while the ERSPC-RC was somewhat better for significant prostate cancer (AUCs 0.73 vs 0.70). Decision curve analyses revealed a comparable net benefit for any prostate cancer and a slightly greater net benefit for significant prostate cancer using the ERSPC-RC. CONCLUSIONS: In our independent external validation, both updated RCs showed less optimistic performance compared with their original reports, particularly for the prediction of any prostate cancer. Risk prediction of significant prostate cancer, which is important to avoid unnecessary biopsies and reduce over-diagnosis and overtreatment, was better for both RCs and slightly superior using the ERSPC-RC.

Primary study

Unclassified

European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study.

Journal BJU international
Year 2016
Liens Pubmed DOI
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OBJECTIVE: To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and two iterations of the European Randomised Study of Screening for Prostate Cancer (ERSPC) Risk Calculator, one of which incorporates prostate volume (ERSPC-RC) and the other of which incorporates prostate volume and the prostate health index (PHI) in a referral population (ERSPC-PHI). PATIENTS AND METHODS: The risk of prostate cancer (PCa) and significant PCa (Gleason score ≥7) in 2001 patients from six tertiary referral centres was calculated according to the PCPT-RC and ERSPC-RC formulae. The calculators' predictions were analysed using the area under the receiver-operating characteristic curve (AUC), calibration plots, Hosmer-Lemeshow test for goodness of fit and decision-curve analysis. In a subset of 222 patients for whom the PHI score was available, each patient's risk was calculated as per the ERSPC-RC and ERSPC-PHI risk calculators. RESULTS: The ERSPC-RC outperformed the PCPT-RC in the prediction of PCa, with an AUC of 0.71 compared with 0.64, and also outperformed the PCPT-RC in the prediction of significant PCa (P<0.001), with an AUC of 0.74 compared with 0.69. The ERSPC-RC was found to have improved calibration in this cohort and was associated with a greater net benefit on decision-curve analysis for both PCa and significant PCa. The performance of the ERSPC-RC was further improved through the addition of the PHI score in a subset of 222 patients. The AUCs of the ERSPC-PHI were 0.76 and 0.78 for PCa and significant PCa prediction, respectively, in comparison with AUC values of 0.72 in the prediction of both PCa and significant PCa for the ERSPC-RC (P = 0.12 and P = 0.04, respectively). The ERSPC-PHI risk calculator was well calibrated in this cohort and had an increase in net benefit over that of the ERSPC-RC. CONCLUSIONS: The performance of the risk calculators in the present cohort shows that the ERSPC-RC is a superior tool in the prediction of PCa; however the performance of the ERSPC-RC in this population does not yet warrant its use in clinical practice. The incorporation of the PHI score into the ERSPC-PHI risk calculator allowed each patient's risk to be more accurately quantified. Individual patient risk calculation using the ERSPC-PHI risk calculator can be undertaken in order to allow a systematic approach to patient risk stratification and to aid in the diagnosis of PCa.

Primary study

Unclassified

European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

Journal Urology
Year 2017
Liens Pubmed DOI
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OBJECTIVE: To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. MATERIALS AND METHODS: We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. RESULTS: Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. CONCLUSION: We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy.

Primary study

Unclassified

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

Journal Annals of internal medicine
Year 2017
Liens Pubmed DOI PubMed Central
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<b>BACKGROUND: </b>The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction.<b>OBJECTIVE: </b>To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO.<b>DESIGN: </b>Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models.<b>SETTING: </b>Randomized controlled trials in Europe and the United States.<b>Participants: </b>Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization.<b>Intervention: </b>Prostate cancer screening.<b>Measurements: </b>Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began.<b>RESULTS: </b>Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening.<b>Limitation: </b>The MLT is a simple metric of screening and diagnostic work-up.<b>CONCLUSION: </b>After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality.<b>Primary Funding Source: </b>National Cancer Institute.

Primary study

Unclassified

Estimate of Opportunistic Prostate Specific Antigen Testing in the Finnish Randomized Study of Screening for Prostate Cancer.

Journal The Journal of urology
Year 2017
Liens Pubmed DOI
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PURPOSE: Screening for prostate cancer remains controversial, although ERSPC (European Randomized Study of Screening for Prostate Cancer) showed a 21% relative reduction in prostate cancer mortality. The Finnish Randomized Study of Screening for Prostate Cancer, which is the largest component of ERSPC, demonstrated a statistically nonsignificant 16% mortality benefit in a separate analysis. The purpose of this study was to estimate the degree of contamination in the control arm of the Finnish trial. MATERIALS AND METHODS: Altogether 48,295 and 31,872 men were randomized to the control and screening arms, respectively. The screening period was 1996 to 2007. The extent of prostate specific antigen testing was analyzed retrospectively using laboratory databases. The incidence of T1c prostate cancer (impalpable prostate cancer detected by elevated prostate specific antigen) was determined from the national Finnish Cancer Registry. RESULTS: Approximately 1.4% of men had undergone prostate specific antigen testing 1 to 3 years before randomization. By the first 4, 8 and 12 years of followup 18.1%, 47.7% and 62.7% of men in the control arm had undergone prostate specific antigen testing at least once and in the screening arm the proportions were 69.8%, 81.1% and 85.2%, respectively. The cumulative incidence of T1c prostate cancer was 6.1% in the screening arm and 4.5% in the control arm (RR 1.21, 95% CI 1.13-1.30). CONCLUSIONS: A large proportion of men in the control arm had undergone a prostate specific antigen test during the 15-year followup. Contamination is likely to dilute differences in prostate cancer mortality between the arms in the Finnish screening trial.