ORLANDO, FL USA (UroToday.com) - In determining personalized risk assessment, the profile of the patient and the tumor should be considered. The baseline risk assessment is an unmet need that could identify men at high-risk and those who might not need therapy. There are numerous challenges with biomarker discovery and validation. For discovery, use of radical prostatectomy specimens is useful but not completely translatable to the untreated patient. A quantifiable, feasible test in small volume material is necessary. The MRI-registered 3D TRUS is more accurate for serial TRUS-guided biopsy. It registers prior biopsy sites and identifies target lesions. Prospective clinical datasets are needed for uniform standards and validation. Single institution data must move to pooled multi-institution datasets and registration studies such as CANARY PASS, PRIAS, and CALGB.90202. CANARY is an AS protocol trial, multi-institution with accrual and development of a urine and tissue biorepository for biomarker delineation. Biomarkers in development are now combined in a systems approach, such as the Aureon assay. Serum markers such as TGF-B1 and IL6 receptor levels were individually discovered, then externally validated. PAI-1 is also shown to improve prediction of PSA in multivariate analysis. However, there is a lack of clinical application of these markers. Urine markers such as PCA3 mRNA are specific and sensitive with low test-to-test variation. An elevated PCA3 score is two-fold more predictive of a positive biopsy. A high score correlates with CaP tumor volume in surgical specimens, however a threshold value for high-risk disease is unclear. A threshold value for determining disease progression in an AS cohort has been unsuccessful, but may have been limited by technical aspects. The ETS gene fusion as a single marker is not emerging as prognostic, but a panel of gene fusions may be predictive, especially when combined with clinical characteristics. Expanding from a single gene locus to genome wide hybridization offers an unbiased, high-resolution approach. Array CGH added to the Kattan nomogram improved predictive ability. Integrative genomic profiling defined transcriptomes and copy number abnormalities (CNAs) in prostate tumors. This identified distinct subgroups with clear differences in time to PSA relapse based upon this technology (Taylor BS, Cancer Cell 2010;18:11-22). Copy number abnormalities identified by the Affymetrix MIPS are new technology to detect CNAs from small segments of DNA. Convergence of genomic, imaging and clinical science will support engineered advances in the future, Dr. Gleave concluded.
Presented by Martin Gleave, MD, FRCSC, FACS at the 2011 Genitourinary Cancers Symposium, General Session I: Emerging Trends in the Characterization and Treatment Decisions in Newly Diagnosed Prostate Cancer - February 17-19, 2011 - Orlando World Center Marriott, Orlando, Florida USA