Prostate cancer screening in Tyrol, Austria: Experience and results

Background: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate-specific antige n (PSA) and percent free PSA as the initial test. Methods: The twelve proje cts studied included: (1) a mass screening study using PSA as the initial t est in 21,079 volunteers; (2) an investigation of the usefulness of normal and age-referenced PSA cut-offs in 1,618 men; (3) a PSA-based screening stu dy of 2,272 asymptomatic blood donors; (4) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative dig ital rectal examination findings; (5) determination of percent free PSA in one retrospective and two prospective studies to determine the appropriate cutpoints for percent free PSA; (6) evaluation of the diagnostic benefit of PSA transition zone density in 308 screening volunteers; (7) a study of th e impact of PSA-based screening on the percentage of incidental prostate ca rcinoma in 1,543 men undergoing transurethral resection of the prostate; (8 ) an evaluation of the changes in total PSA and pathologic stages in radica l prostatectomy over 5 years in a PSA-based mass screening program; (9) a s tudy evaluating the probability of having prostate cancer given the patient 's age, total PSA and digital rectal examination findings; (10) an evaluati on of the correlation between preoperative predictors and pathologic featur es in radical prostatectomy specimens; (11) an investigation of the correla tion of-total PSA with pathologic stage and tumor volume in patients underg oing radical prostatectomy with low PSA cut-off level, and (12) a study whe ther age has an impact on the extension of prostate cancer. Results: (1) of the 21,079 volunteers, 1,618 (8%) had elevated PSA levels. Of these men, 7 78 (48%) underwent biopsies; 197 biopsies were positive for prostate carcin oma and 135 underwent radical prostatectomy. Ninety-five were found to be o rgan-confined. (2) A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and o f 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detec tion rate of organ-confined disease. (3) Of the 2,272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients und erwent radical prostatectomy and histologic examination revealed organ-conf ined tumor in all but 8 men. (4) Ninety-eight of 340 men had biopsies posit ive for carcinoma; 28 of these patients (28.5%) had carcinoma that originat ed in the transition zone only. (5) In the retrospective study, receiver-op erating characteristic curve analysis showed that by using a percent free P SA of 18% as a biopsy criterion, 37% of the negative biopsies could be elim inated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated PSA levels <10.0 ng/ml wer e further evaluated and 37 prostate carcinomas were detected. By using a % free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In th e second prospective study, 120 of 465 men with total PSA levels between 1. 25 and 6.49 ng/ml and a % free PSA <18% were further evaluated and 27 (22.5 %) were found to have prostate carcinomas. (6) Receiver-operating character istic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of >22 ng/ml/cm(3) as a biopsy criterion, 24.4 % of negative biopsies could be avoided without missing a single carcinoma. (7) In the prescreening era the incidence of T1a grade 1 and 2 carcinomas was 3.1% and the incidence of T1a grade 3 and T1b carcinoma was 2. 3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. (8) The rate of organ-confined tu mors increased from 28.7% in 1993 to 65.7% in 1997. (9) In this evaluation a new approach to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cutpoint was develo ped. (10) High total PSA levels, PSA density and PSA transition zone densit y correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. (11) In this evaluation all of the 95 patients with PSA levels <3. 99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. (12) The re sults of this evaluation suggest that older men have larger tumor volumes c ompared to younger men with the same PSA levels. Conclusions: These data su ggest that PSA-based screening with low PSA cut-off va rues increase the de tection rate of clinically significant, organ-confined and potentially cura ble prostate cancer. Percent free PSA and PSA transition zone density provi de an additional diagnostic benefit over total PSA.