Prostate-specific antigen-based early detection of prostate cancer--validation of screening without rectal examination.

OBJECTIVES: The evaluation of the screening procedures for prostate cancer (PCa) was a part of the protocol of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, The Netherlands. We sought to establish an improved strategy for the early detection of PCa using a prostate-specific antigen (PSA) cutoff of 3.0 ng/mL or greater as the only indication for prostate biopsy with omission of the digital rectal examination (DRE). METHODS: In June 1996, 8612 men, 55 to 74 years old, were randomized to screening and were screened within the ERSPC Rotterdam by a PSA level of 4.0 ng/mL or greater or positive DRE or transrectal ultrasound findings as the indication for biopsy. Four hundred thirty men had PCa. Those treated by radical prostatectomy provided the tumor characteristics considered essential for a change in the screening strategies. Various options were evaluated and predictions made by logistic regression analyses. The protocol change was implemented in February 1997. Another 7943 men were screened according to the new protocol (PSA 3.0 ng/mL or greater). The resulting data were used to compare the two protocols. RESULTS: The detection rate (proportion of PCa in those screened) turned out to be very similar, with rates of 5.0 and 4.7 at a PSA cutoff of 4.0 ng/mL or greater and 3.0 ng/mL or greater, respectively. This was due to a much larger number of cases of PCa per biopsy in the PSA range of 3 to 3.9 ng/mL than expected. The positive predictive value of the PSA range 3.0 to 3.9 ng/mL in the two protocols was 18.0% and 6.4%, respectively. Tumor characteristics were studied on radical prostatectomy specimens from the original protocol. PCa detected with the new screening regimen had a similar distribution of Gleason scores but a larger proportion of confined disease. Tumor volumes were smaller in patients with PSA levels of less than 2.9 ng/mL; the proportion of "minimal disease" in that group was 50% compared with 28% in the group with a PSA level between 3.0 and 3.9 ng/mL. CONCLUSIONS: Lowering the biopsy indication to a PSA cutoff of 3.0 ng/mL or greater without a DRE improved the positive predictive value from 18.2% to 24.3%. The number of biopsies necessary to detect 1 case of PCa accordingly changed from 5.2 to 3.4. The overall characteristics of the cases detected at that PSA cutoff differed very little from those detected with the regimen based on PSA, DRE, and transrectal ultrasound.