The European randomized study of screening for prostate cancer
1997; Wiley; Volume: 80; Issue: 9 Linguagem: Inglês
10.1002/(sici)1097-0142(19971101)80
ISSN1097-0142
Autores Tópico(s)Colorectal Cancer Screening and Detection
ResumoCancerVolume 80, Issue 9 p. 1830-1834 CommunicationFree Access The European randomized study of screening for prostate cancer† An update Bo Standaert M.D., Corresponding Author Bo Standaert M.D. Oncology Centre Antwerp, A. Z. Middelheim, Antwerp, BelgiumAvenue Ariane 5, 1200 Brussels, Belgium===Search for more papers by this authorLouis Denis M.D., Louis Denis M.D. Oncology Centre Antwerp, A. Z. Middelheim, Antwerp, BelgiumSearch for more papers by this author Bo Standaert M.D., Corresponding Author Bo Standaert M.D. Oncology Centre Antwerp, A. Z. Middelheim, Antwerp, BelgiumAvenue Ariane 5, 1200 Brussels, Belgium===Search for more papers by this authorLouis Denis M.D., Louis Denis M.D. Oncology Centre Antwerp, A. Z. Middelheim, Antwerp, BelgiumSearch for more papers by this author First published: 20 November 2000 https://doi.org/10.1002/(SICI)1097-0142(19971101)80:9 3.0.CO;2-5Citations: 32 † Presented at the American Cancer Society Workshop: Review of Current Data Impacting Early Detection Guidelines for Prostate Cancer, Phoenix, Arizona, March 10-11, 1997. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract BACKGROUND A consensus meeting on screening and global strategy for prostate carcinoma, held in Antwerp in 1994, determined the willingness among European cancer prevention centers to pursue vigorously the collaborative formation of a multinational randomized screening trial. This trial was to be named the European Randomized Study of Screening for Prostate Cancer (ERSPC). METHODS During the years prior to that meeting, several feasibility trials were conducted in Antwerp and Rotterdam to evaluate the pitfalls and problems of a randomized procedure for population screening. Today, five centers in five European countries share their study work and results via the ERSPC, and others are lining up to join this massive effort. Regular meetings and specific work groups enable the research centers to compare their data, because the trial methodology differs slightly from one center to another. RESULTS However, a common work strategy and analysis of the data has recently been reached, and the first study results of the trial (evaluating 180,000 men over a 10-year screening period) are expected by the year 2007. CONCLUSIONS A randomized trial of prostate carcinoma screening is set up in Europe currently with five participating centers from five countries. First overall effect results of regular screening are expected after a 10-year period of follow-up. Cancer 1997; 80:1830-4. © 1997 American Cancer Society. Prostate carcinoma, a disease that affects mainly older men, is becoming a huge health care problem in the Western world because the male population is aging. In many European countries prostate carcinoma has become the second most common malignancy among the male population after lung carcinoma, with an estimated annual incidence for Europe of 85,000 cases diagnosed each year and a mortality rate of 35,000 per year.2 Currently, three tests mainly are used to detect early prostate carcinoma. However, it is still unclear as to in which order they should be performed and how to reach the most efficient strategy of secondary prevention that reduces the specific mortality of prostate carcinoma.3 Different study designs are available that could help to solve this major epidemiologic challenge. One way recommended by the European prevention centers is to establish a randomized, prospective trial.1 Although patients will undergo the screening procedure under study, controls will undergo the procedures used in common clinical practice. This ambitious project received the approval of the Europe against Cancer organization in 1992. In this study, the authors present an update of this research study, which attempts to solve the enigma of prostate carcinoma: to screen or not to screen.4 METHODS The objective and the method used by the European Randomized Study of Screening for Prostate Cancer (ERSPC) have been described and reported in previous publications.5, 6 A summary of the current situation is presented in Table 1 and Figure 1 (7K). In addition to the biannual meetings of the scientific committee, during which the results of the participating centers are presented and discussed, a series of working committees has been established. The committees are meant to solve the delicate problems related to data collection and transmission from the different participating centers, from the surveillance of the validity of the prostate specific antigen (PSA) test used to the evaluation of the anatomopathology of the biopsies taken. The death certificate working group checks the common procedure to evaluate the causes of death of the participants. The internal quality control working group verifies the uniform working quality in the participating centers. Figure 1Open in figure viewerPowerPoint Flow chart of the participants into the trial in Antwerp, Belgium. PSA: prostate specific antigen; DRE: digital rectal examination; TRUS: transrectal ultrasound. Table 1. Objectives and Methods of the ERSPC Objectives of the ERSPC To demonstrate whether the effect of screening causes specific mortality reduction of at least 20% To identify the best screening method by selecting the most appropriate combination of available screening tests To identify risk groups who will benefit most from the screening process To evaluate the quality of life of the participants and the cost-effectiveness of the screening program Methods of the ERSPC Pooled analysis of ongoing and planned screening programs Minimum set of information per center required including: randomization process, age group selected, test selection and procedure, treatment chosen, and follow-up, including causes of death ERSPC: European Randomized Study of Screening for Prostate Cancer. An independent data monitoring committee to which each participating center reports its data regularly identifies which participating center fulfils the criteria of admission. This committee also established the endpoints at the start of the trial. Knowing the operating differences between the collaborating centers, the challenge is to determine whether the data collected are suitable for a meta-analysis that adjusts for covariates such as age, prostate volume, number and type of screening tests used, and number of biopsies taken for each suspected case.6 RESULTS Table 2 presents the common and currently different approaches performed by each participating center in conducting its randomized trial. Differences are observed among the age groups that should enter the screening trial, which screening tests are used and when, which test criteria per screening test is selected to classify participants suspected of malignancy, the rescreening interval, and when to perform the randomization (before or after participation consent is obtained). Table 2. Current Collaborating Centers with Conditions of Participation Belgium Finland Italy The Netherlands Sweden Endpoints Mortality + + + + + QOL + + + + + C/E + + + + + Trial type Pop. ref. Pop. ref. Pop. ref. Pop. ref. Pop. ref. Recruitment Pop. regis. Pop. regis. Pop. regis. Pop. regis. Pop. reg. Age selection (yrs) 55-74 55-67 50-69 55-74 50-65 Screening PSA 4 ng/mL 2/4 ng/mL 4 ng/mL 4 ng/mL 3 ng/mL DRE + PSA > 2, no + + No TRUS + No No + No Interval (yrs) 4 4 4 4 4 Mortality Death certificate Death certificate Death certificate Death certificate Death certificate Numbers >20,000 >65,000 >50,000 >35,000 >30,000 Randomization After consent After consent After consent After consent Before consent QOL: quality of life; C/E: cost-effectiveness; Pop. ref.: population reference; Pop. regis: population registry; PSA: prostate specific antigen; DRE: digital rectal examination; TRUS: transrectal ultrasound; +: positive; -: negative. An agreement to eliminate transrectal ultrasound as a primary test will go into effect in the near future. Although the test can detect early carcinomas confined to the prostate gland that cannot be detected by the other two screening tests used (digital rectal examination [DRE] and PSA), its false-positive rate is too high to include it in routine screening.7 Table 3 and Figure 2 (6K) summarize data regarding PSA values observed in the Netherlands and in Belgium related to biopsy outcome. The only differences found between the centers are low PSA ranges caused by the different selection criteria used per center to perform a biopsy. However, the data suggest for both centers a PSA screening threshold value of 3 ng/mL rather than 4 ng/mL. It currently is unclear whether adjustments to prostate volume and/or age should be made to decrease the numbers of biopsies taken per carcinoma detected in the patients whose PSA ranges between 4-9.9 ng/mL. Figure 2Open in figure viewerPowerPoint Identification of the type of carcinoma in relation to the prostate specific antigen (PSA) value from 172 biopsy results. Pos: positive. Table 3. PSA Values and Related Biopsy Results for Belgium (n = 3942) and the Netherlands (n = 3963) PSA range (ng/mL) 0-0.9 1-1.9 2-2.9 3-3.9 4-9.9 >10 Screened B 31.7% 30.5% 14.8% 7.6% 11.6% 3.6% N 34.62% 32.05% 12.89% 7.01% 11.28% 2.15% Biopsies B 2.9% 3.5% 5.6% 6.2% 27.5% 57% N 12.5% 14.7% 16.4% 7.1% 94% 91% Carcinoma B 16% 8.3% 10.7% 31% 18.7% 52.1% N 2.3% 5.3% 14.2% 20.5% 22% 57% Bx/Pc B 6.2 12 9.3 3.2 5.35 1.9 N 43 18.7 7 4.9 4.5 1.7 PSA: prostate specific antigen; B: Belgium; N: the Netherlands; Bx/Pc: biopsy. Finally the comparison between reported data from Sweden, the Netherlands, and Belgium again show differences in the rate of biopsies taken per carcinoma detected in patients with a PSA range < 4 ng/mL (Fig. 3 (10K)). The difference is explained primarily by the different age groups selected for the screening. Figure 3Open in figure viewerPowerPoint Biopsies taken per carcinoma detected for different prostate specific antigen (PSA) ranges and different centers. B: Belgium (n = 192); Sw: Sweden (n = 609); N: the Netherlands (n = 538). DISCUSSION A multinational, randomized screening trial for prostate carcinoma has been fully functional in Europe for the past 2 years. To the authors' knowledge, until now, no rescreening of the target population has taken place in any of the five participating centers. As observed from the reported results, there are some discrepancies among the data collected in each center. These discrepancies are related to the key variables selected by each participating center that cause differences in carcinoma detection rates among the centers. The variables include age groups selected, screening tests used, and screening criteria selected per test. To facilitate the analysis of the pooled data from the collaborating centers, a uniform approach must be established. Recently consensus has been reached among the participating centers that the data after transfer will be analyzed at one data center located at the University of Edinburgh, United Kingdom. Regardless of the current analysis of the data collected, two critical points will be continuously assessed. First is the need to limit the mean number of biopsies taken per detected relevant carcinoma and the second is to monitor carefully the sample size required. To solve the first problem, selection criteria based on the two screening tests used (PSA and DRE) will be defined for the at-risk group in which an acceptable mean biopsy rate to detect a relevant carcinoma (biopsy/Pc) is approximately < 4. In that respect, it has been suggested that selecting participants with a PSA level > 3 ng/mL adjusted for prostate volume and/or with DRE will procure the best results.7 To observe a significant decline of 20% in specific mortality caused by the screening, a sample size of 90,000 participants in each treatment arm is warranted. The potential contamination rate of the control group involuntarily receiving a PSA test (estimated at 10- 15% in the trial) is not included into this calculation, nor is the observed decline of 10% in the compliance rate among the case group. Adjustment for both factors may increase the sample size to 110,000 participants in each arm. This objective is vast but in reach of a number of candidate centers from Spain, the United Kingdom, Portugal, Belgium, and the Netherlands that are ready and prepared to join these screening efforts with the goal of bringing this ambitious project to a definitive conclusion. CONCLUSIONS A randomized, population-based screening trial for prostate carcinoma requires significant efforts to organize a number of collaborating centers to obtain a sample size that is relevant to prove the benefit of the screening. It also requires an appropriate approach and consensus of the participating centers with regard to the selection of key variables that enable researchers to proceed with a meta-analysis of the pooled data. Hopefully, these different hurdles will be overcome and the ERSPC will succeed in its effort so that first results of the trial could be reported by the year 2007. REFERENCES 1 Denis L, Murphy GP, Schröder FH. Report of the Consensus Workshop on Screening and Global Strategy for Prostate Cancer. Cancer 1995; 75: 1187- 207. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 2 Moller Jensen O, Estève J, Moller H, Renard H. Cancer in the European Community and its member states. Eur J Cancer 1990; 26: 1167- 256. CrossrefCASPubMedWeb of Science®Google Scholar 3 Boyle P, Alexander FE, Standaert B, Denis L. Screening for prostate cancer. In: R Kirby, editor. Recent advances in urology/andrology. Volume 6. Edinburgh: Churchill-Livingstone, 1993: 139- 57. Google Scholar 4 Schröder FH. Prostate cancer: to screen or not to screen? BMJ 1993; 306: 407- 8. CrossrefCASPubMedWeb of Science®Google Scholar 5 Schröder FH, Denis L, Kirkels W, de Koning HJ, Standaert B. European Randomized Study of Screening for Prostate Cancer. Cancer 1995; 76: 129- 34. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 6 Auvinen A, Rietbergen JBW, Denis LJ, Schröder FH, Prorok PC. Prospective evaluation plan for randomised trial of prostate cancer screening. J Med Screen 1996; 3: 97- 104. CrossrefCASPubMedGoogle Scholar 7 Standaert B, Alwan A, Nelen V, Denis LJ. Prostate volume in cancer screening. Prostate. In press. 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