Biomarkers in Prostate Cancer在前列腺癌生物标记.pptVIP

Biomarkers in Prostate Cancer Prostate Cancer Symposium The Prostate Net September 17, 2011 Steven Lucas Wayne State University School of Medicine Karmanos Cancer Institute Why are Biomarkers Important Prostate Cancer diagnosed in 200,000 men annually in the united states 30,000 cancer specific deaths per year Yet, a substantial portion of cancers diagnosed through PSA screening do not progress to clinically significant disease. Problem with PSA screening It is not specific, resulting in a negative biopsy rate of up to 70% in some series European randomized trial: 1410 men screened and 48 treated to prevent 1 death from prostate cancer Sweedish Randomized trial of watchful waiting: Relative risk for surgery: 0.62 (0.44-0.87) NNT 15 overall and 7 for men younger than 65y How do we improve screening and treatment decisions? Clinical nomograms Include Gleason Score, positive cores, percent involvement of cores, and PSA Other risk factors: family history, age, race Biomarkers Supplement known clinical information Clinical Nomogram: Kattan Nomogram Stephenson et al, J natl CI, 2006 How can biomarkers improve management? Categories of biomarkers Urine Based Blood Based Tissu Based Urine Based Biomarkers Proteins Urinary/serum psa ratio Annexin A3 MMP9 Proteomics DNA Glutathione-S-transferase P1 Other methylation- specific PCR assays RNA PCA3 TMPRSS2-ERG gene fusion Roobol et al, Acta oncologica, 2011 Urinary PCA3 Developed from differential expression of noncoding RNA’s in prostate cancer versus other prostate conditions Commercially available, approved diagnostic test Collected from urine sample following a firm DRE Could function as a first line screen or prognostic indicator Urinary PCA3: First line screen Several studies show superior overall specificity to PSA: 80-90%, but include only patients with elevated PSA In the REDUCE trial the placebo test characteristics for PSA were: Se = 0.518 Sp = 0.629 PCA3 in patients with PSA 4-10ng/ml: