Background: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate-specific antigen (PSA) and percent free PSA as the initial test.
Methods: The twelve projects studied included: (1) a mass screening study using PSA as the initial test 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 study of 2,272 asymptomatic blood donors; (4) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative digital 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 the impact of PSA-based screening on the percentage of incidental prostate carcinoma in 1, 543 men undergoing transurethral resection of the prostate; (8) an evaluation of the changes in total PSA and pathologic stages in radical prostatectomy over 5 years in a PSA-based mass screening program; (9) a study evaluating the probability of having prostate cancer given the patient's age, total PSA and digital rectal examination findings; (10) an evaluation of the correlation between preoperative predictors and pathologic features in radical prostatectomy specimens; (11) an investigation of the correlation of total PSA with pathologic stage and tumor volume in patients undergoing radical prostatectomy with low PSA cut-off level, and (12) a study whether 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, 778 (48%) underwent biopsies; 197 biopsies were positive for prostate carcinoma and 135 underwent radical prostatectomy. Ninety-five were found to be organ-confined. (2) A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection 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 underwent radical prostatectomy and histologic examination revealed organ-confined tumor in all but 8 men. (4) Ninety-eight of 340 men had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transition zone only. (5) In the retrospective study, receiver-operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated 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 were 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 the 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 characteristic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of >22 ng/ml/cm3 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 tumors 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 rath