Meta-analysis of PSA, DRE and TRUS According to the rapid advances in diagnostic technology, new diagnostic procedures like PSA and TRUS were introduced to the Korean Medical Association (KMA) in the early 1980s, and many Korean studies on this diagnostic triad of PSA, DRE and TRUS for the diagnosis of prostate can- cer have been undertaken since the early 1990s. The widespread application of diagnostic tech- niques, and especially PSA and systematic bio- psies, have played an important role in the in- creased incidence of prostate cancer.3,40 Also, the issues concerning clinical practice guidelines (CPGs) have also established after 1990 by the KMA,41 and the Korean Urological Association began developing the CPGs for prostate cancer a couple of years ago. Therefore, in this study, we conducted a meta-analysis of PSA, DRE, and TRUS for diagnosing prostate cancer among those subjects with lower urinary symptom, and we particularly focused on sensitivity and specificity according to the eligibility of some databases, like Medline, when searching for Korean articles published since the mid-1990s. Because the outcome data used in this study were based on retrospective observational studies, there would be considerable variation for the results of primary studies of this diagnostic triad. Furthermore, it was proved that 13 studies were heterogeneous with a statistical significance for both DRE and TRUS criteria, unlike the PSA cri- teria (PSA4 and PSA10). This variation may have been caused by chance alone (the small sample sizes), but it can also reflect true heterogeneity. Possible clinical sources of such heterogeneity are the between-study differences for the type of test that was used, the selected positivity cutoff point of each test, the patient selection and clinical setting, deficiencies in study design (methodolo- gical heterogeneity), or any combination of these factors.42,43 To minimize variations of study quality in the meta-analysis for the diagnostic tests, the Cochrane Methods Working Group on Screening and Diagnostic Tests have suggested that the comprehensive validity checklist for pri- mary studies include the study population's re- cruitment, the patient selection method (selection bias), the verification method (differential refer- ence standard bias), the interpretation of tests method, and the method to avoid residual con- founding.44,45 Therefore, this meta-analysis used only those studies that met the inclusion criteria (including using biopsy results as a reference standard and excluding screening tests on general population46,47) for quality evaluation. Also, because the search was restricted to Korean- language studies, there may be a considerable (English) language bias. In addition, to eliminate any multiple publication bias when there were several articles (including any masters thesis) written by the same authors, clinical data from the most recent publication were used.48 Among the several major outcomes of this meta-analysis, the most important outcome was the comparison of PSA, DRE and TRUS as diag- nostic tests to detect prostate cancer. The overall sensitivity and overall specificity for PSA4 were 91.3% and 35.9%, respectively; and those for PSA10 were 77.3% and 67.5%, respectively. Also, those for DRE were 68.4% and 71.5%, respectively; and those for TRUS were 73.6% and 61.3%, re- spectively. If a Korean man with lower urinary symptoms has abnormal PSA levels or DRE or TRUS findings, the chances of him having cancer are about 2 in 5; conversely, when the PSA levels or findings on DRE or TRUS are normal, the chance of missing the cancer is about 10%. Also, the detection rate (50.0%) of combination testing of PSA10 and DRE were larger than that (44.1% or 45.0%) of PSA10 or DRE alone. Further, the detection rate of combination testing of PSA4 or PSA10 with DRE and TRUS jumped to 68.3% or 76.8%. Thus, when this diagnostic triad was ab- normal, our result (the probability of prostate cancer) is same or is larger than that (68%) of the Haid et al. study.18 What exactly does all this mean to the clinician? It means that diagnostic triad for the detection of prostate cancer in men with lower urologic symptoms is a useful tool. Once the PSA is elevated more than 10 ng/mL or the DRE and TRUS are abnormal, then an invasive procedure with close follow-up appears to be necessary. However, a PSA of greater than 4.0 ng/mL has limited specificity because such elevations also occur in men with benign disease (e.g., prostatic hyperplasia and prostatitis). It is well known that PSA values for prostate cancer and benign pro- state hyperplasia have considerable overlap. Yonsei Med J Vol. 46, No. 3, 2005