<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.).
CONTEXTE: La composante de la prostate de la prostate, du poumon, colorectal et ovarien (PLCO) Essai de dépistage du cancer a été menée afin de déterminer si il ya une réduction de la mortalité par cancer de la prostate en utilisant du sérum de dépistage d'antigène prostatique spécifique (APS) et le toucher rectal (DRE). La mortalité après 7-10 ans de suivi a été rapporté précédemment. Nous rapportons un suivi prolongé jusqu'à 13 ans après le procès.
Méthodes: Un total de 76 685 hommes, âgés de 55 à 74 ans, ont été recrutés dans 10 centres de dépistage entre Novembre 1993 et Juillet 2001 et assignés au hasard à l'intervention (dépistage organisé du test PSA annuel de 6 ans et annuelle DRE pour 4 ans; 38 340 hommes) et de contrôle (soins habituels, qui sont parfois inclus dépistage opportuniste; 38 345 hommes) bras. Le dépistage a été achevée en Octobre 2006. Tous les cancers de la prostate incidents et décès de cancer de la prostate à travers 13 ans de suivi ou par le biais Décembre 31, 2009, ont été constatés. Les risques relatifs (RR) ont été estimés comme étant le ratio des taux observés dans les groupes d'intervention et de contrôle, et les intervalles de confiance à 95% (IC) ont été calculés en supposant une distribution de Poisson pour le nombre d'événements. Modèle de régression de Poisson a été utilisée pour étudier les interactions à l'égard de la mortalité par cancer de la prostate entre bras de l'essai et de l'âge, de l'état de comorbidité et préventive test de l'APS. Tous les tests statistiques étaient bilatéraux.
RÉSULTATS: Environ 92% des participants à l'étude ont été suivis jusqu'à 10 ans et de 57% à 13 ans. A 13 ans, 4250 participants avaient reçu un diagnostic de cancer de la prostate dans le groupe d'intervention par rapport à 3815 dans le groupe témoin. Taux d'incidence cumulée de cancer de la prostate dans les groupes d'intervention et de contrôle étaient 108,4 et 97,1 pour 10 000 personnes-années, respectivement, résultant en une augmentation relative de 12% dans le groupe intervention (RR = 1,12, IC 95% = 1,07 à 1,17) . Après 13 ans de suivi, les taux de mortalité cumulatifs du cancer de la prostate dans les groupes d'intervention et de contrôle étaient de 3,7 et 3,4 décès pour 10 000 personnes-années, respectivement, soit une différence non statistiquement significative entre les deux bras (RR = 1,09, IC à 95% = 0,87 à 1,36). Aucune interaction statistiquement significative en ce qui concerne la mortalité par cancer de la prostate ont été observées entre les bras de l'essai et de l'âge (P (interaction) = .81), avant le procès test de l'APS (P (interaction) = .52), et la comorbidité (P (interaction) = 0,68 ).
CONCLUSIONS: Après 13 ans de suivi, il n'y avait aucune preuve d'un avantage de mortalité pour le dépistage annuel organisé à l'essai PLCO par rapport à un dépistage opportuniste, qui fait partie du traitement habituel, et il n'y avait aucune interaction apparente avec comorbidité de base au vieillissement, ou des tests PSA provisoire.
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.
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.
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.
<b>BACKGROUND: </b>In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.<b>METHODS: </b>From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model.<b>RESULTS: </b>During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4).<b>CONCLUSIONS: </b>Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).
OBJECTIF: Évaluer si le dépistage du cancer de la prostate réduit la mortalité spécifique de la prostate.
CONCEPTION: La population est basée essai contrôlé randomisé.
CONTEXTE: Département d'urologie, Norrköping et le Sud-Est Région cancer de la prostate registre.
PARTICIPANTS: Tous les hommes âgés de 50-69 dans la ville de Norrköping, en Suède, identifié en 1987 dans le registre national de population (n = 9026).
INTERVENTION: De la population de l'étude, 1494 hommes ont été affectés au hasard à être projeté en incluant tous sixième homme à partir d'une liste de dates de naissance. Ces hommes ont été invités à dépister tous les trois ans de 1987 à 1996. Sur les deux premières fois, le dépistage a été fait par le toucher rectal seulement. A partir de 1993, elle a été associée à des tests de l'antigène prostatique spécifique, avec 4 ug / L comme coupée. À la quatrième occasion (1996), seuls les hommes âgés de 69 ans ou moins au moment de l'enquête ont été invités.
Principaux critères de jugement: Les données sur le stade tumoral, le grade et le traitement de la région sud-est de la prostate Cancer S'enregistrer. Cancer de la prostate mortalité spécifique jusqu'au 31 Décembre 2008.
RÉSULTATS: Dans les quatre projections de 1987 à 1996 participation a été de 1161/1492 (78%), 957/1363 (70%), 895/1210 (74%), et 446/606 (74%), respectivement. Il y avait 85 cas (5,7%) de cancer de la prostate dans le groupe dépisté et 292 (3,9%) dans le groupe témoin. Le taux de risque de décès par cancer de la prostate dans le groupe dépistage était de 1,16 (intervalle de confiance 95% 0,78 à 1,73). Dans une analyse de risque proportionnel de Cox comparant cancer de la prostate survie spécifique dans le groupe témoin que dans le groupe de dépistage, le risque relatif de décès par cancer de la prostate était de 1,23 (0,94 à 1,62, p = 0,13). Après ajustement pour l'âge au début de l'étude, le risque relatif était de 1,58 (1,06 à 2,36, p = 0,024).
CONCLUSIONS: Après 20 ans de suivi du taux de décès par cancer de la prostate ne diffèrent pas significativement entre les hommes dans le groupe de dépistage et ceux du groupe témoin. Enregistrement de l'essai Current Controlled Trials, ISRCTN06342431.
<b>PURPOSE: </b>Estimates of prostate cancer-specific mortality (PCSM) were similar for men randomly assigned to intervention compared with usual care on the Prostate, Lung, Colorectal and Ovarian PC screening study. However, results analyzed by comorbidity strata remain unknown.<b>Patients and METHODS: </b>Between 1993 and 2001, of 76,693 men who were randomly assigned to usual care or intervention at 10 US centers, 73,378 (96%) completed a questionnaire that inquired about comorbidity and prostate-specific antigen (PSA) testing before random assignment. Fine and Gray's multivariable analysis was performed to assess whether the randomized screening arm was associated with the risk of PCSM in men with no or minimal versus at least one significant comorbidity, adjusting for age and prerandomization PSA testing.<b>RESULTS: </b>After 10 years of follow-up, 9,565 deaths occurred, 164 from PC. A significant decrease in the risk of PCSM (22 v 38 deaths; adjusted hazard ratio [AHR], 0.56; 95% CI, 0.33 to 0.95; P = .03) was observed in men with no or minimal comorbidity randomly assigned to intervention versus usual care, and the additional number needed to treat to prevent one PC death at 10 years was five. Among men with at least one significant comorbidity, those randomly assigned to intervention versus usual care did not have a decreased risk of PCSM (62 v 42 deaths; AHR, 1.43; 95% CI, 0.96 to 2.11; P = .08).<b>CONCLUSION: </b>Selective use of PSA screening for men in good health appears to reduce the risk of PCSM with minimal overtreatment.
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.).
