Prostate-specific antigen (PSA) screening significantly increases the early diagnosis of prostate cancer; however, the specificity of PSA screening is fairly low (20%), leading to many unnecessary biopsies and overtreatment. Hence, the identification of a circulating biomarker with high specificity to complement the traditional PSA test is greatly needed. CpG island promoter hypermethylation may be one of the earliest somatic genome alterations in the development of several types of cancers. Studies have shown that glutathione-s-transferase-π (GST-P1) promoter hypermethylation is the most common somatic genome alteration during prostate cancer development. We have retrieved 22 studies that measured GST-P1 in plasma, urine, buffy coat, ejaculate, or whole blood. In our random effect model, the pooled specificity of measurement of GST-P1 hypermethylation was 89% (95%CI, 71-95%), indicating that GST-P1 has a much stronger specificity than the PSA test. When we stratify the studies by biospecimen type and PCR method, high specificity remains within each stratum. Unlike the PSA test, the pooled sensitivity of the GST-P1 methylation test was 47% (95%CI, 33-61%), relatively low. However, low sensitivity does not downgrade its potential application as a complement to the PSA test, which has a high sensitivity but a poor specificity. Moreover, we have found that the likelihood of GST-P1 methylation tends to increase with prostate cancer pathological stage (stages 3-4 versus 1-2), with an odds ratio of 1.21 (95%CI, 0.99-1.48). However, due to limited sample size (10 studies), this did not reach statistical significance. The current study has several advantages. This is the first study to systemically review GST-P1 methylation as measured in body fluids, and to compare the specificity of GST-P1 to the traditional PSA test; second, this review has rigorously examined specificity by excluding healthy controls, who cannot represent individuals with elevated PSA levels or urological symptoms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2797.