In the community of Göteborg (population, 440 000), as of December 31, 1994, there were 32298 men alive who had been born between January 1, 1930, and December 31, 1944. After permission was obtained from the ethical committee, with the aid of the Swedish Population Registry, 10 000 men from this group (aged 50–65 years) were randomized by computer to prostate cancer screening and 10 000 men were randomized to serve as the control group. Men with prevalent prostate cancer were excluded, resulting in an intervention group of 9972 men and a control group of 9973 ().
Study design. See the “Methods” section for details. PSA indicates prostate-specific antigen.
The screening group received first-time invitations for PSA testing from January 1995 to December 1996. Serum was separated from blood tells, frozen, and stored at −20°C within 3 hours. The PSA was measured (Delfia Prostatus PSA F/T Dual Assay; Perkin Elmer Life Sciences, Turku, Finland) within 2 weeks from sample collection and less than 3 hours after thawing, Free and complex PSA forms are detected in an equimolar fashion by this assay. The lower limit of detection is 0.05 ng/mL; coefficients of variation are 13.9% at low (0.34 ng/mL), 5.6% at medium (2.30 ng/mL), and 5.5% at high (20.60 ng/mL) PSA levels. Men with PSA levels less than 3.00 ng/mL were not further studied, while men with PSA levels of 3.00 ng/mL or more were invited for further workup by an experienced urologist, consisting of digital rectal examination (DRE), transrectal ultrasound, and laterally directed sextant biopsies.6
Men with benign results of biopsies and PSA levels of 7.00 ng/mL or more were invited for new PSA testing after 6 months, and repeat biopsies were offered when PSA levels remained elevated.
Men with PSA levels less than 3.00 ng/mL and men with benign results of biopsies were invited for repeated PSA-based screening after 2 years (during 1997 and 1998), after 4 years (during 1999 and 2000), and after 6 years (during 2001 and 2002). Invitations for the second and fourth rounds of screening followed the same algorithm as the first. In the third round of screening, men with PSA levels less than 1.00 ng/mL during the second round of screening were not invited, The reason for this was that none of the 2950 men with PSA levels less than 1.00 ng/mL in the first round were found to have PSA levels greater than 3.00 ng/mL during the second round. However, the PSA cutoff that resulted in further investigations was lowered from 3.00 to 2.54 ng/mL for consistency within the European Randomized Screening Study for Prostate Cancer. Therefore, men with negative results of biopsies and persistently elevated PSA levels in the subsequent biennial testing may have been invited for biopsy up to 4 times during 7 to 8 years.
The present study is based on all 5855 men who participated in the first screening round in 1995 and 1996. The cancer detection rates have been related to their baseline PSA level measured in 1995 and 1996. To ensure inclusion of all cancer cases diagnosed outside the screening program (ie, interval cancers or “wild” extra screening), the study data were cross-matched against the regional cancer registry to identify and include any interval cancers diagnosed up to July 1, 2003.
Projected cumulative estimates of the risk of being diagnosed as having prostate cancer were calculated with the Kaplan-Meier method, and the difference between groups was tested with the Mantel-Cox log-rank test.