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Introduction: To assess the extent of overestimation of the cumulative probability of death by the Kaplan-Meier method with the competing-risks regression analysis as reference approach., Materials and Methods: Data were derived from the screening arm of the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The screening arm consisted of 21210 men between the ages of 55 and 74 at study entry. Follow up concerning mortality was complete through 2008. Endpoints were 5 and 10 year cumulative probabilities of prostate cancer death and death from other causes. Relative bias was defined as the ratio of the cumulative probability of death as determined by the Kaplan-Meier method, relative to the cumulative probability obtained by the competing-risks analysis., Results: According to the Kaplan-Meier method, the 5 year cumulative probability of death from prostate cancer was 0.0101, compared with 0.0099 according to the competing-risk analysis [1.8% overestimation]. At 10 year, these numbers were 0.0347 and 0.0321, respectively [8.0% overestimation]. For death from other causes, the cumulative probabilities at 5 year were 0.0399 and 0.0397 according to the Kaplan-Meier and the competing-risks method [0.6% overestimation], respectively. At 10 year, the probabilities were 0.141 and 0.139 [1.7% overestimation], respectively., Conclusions: When competing events are present, the competing-risks regression analysis is to be preferred over the Kaplan-Meier method in the estimation of the cumulative probability of the event of interest.

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., (Copyright 2002 Wiley-Liss, Inc.)

Screening for prostate cancer is controversial. While in some parts of the world screening is practised as a healthcare policy, it is strongly rejected in other areas, because solid evidence of effectiveness of screening combined with early treatment with respect to lowering the mortality of prostate cancer has not been shown. It is for this reason that a large European study is installed to establish or rule out the value of screening for this frequent disease. The present paper presents the goal of the study and elaborates on the value of presently available screening tests. Preliminary results with respect to the first round of screening in the Rotterdam area relating to 32,000 randomized men are presented. Evidence of effectiveness of screening through other studies and mechanisms is discussed.