Somatic DNA copy number alterations and their potential clinical utility for predicting lethal prostate cancer.

C urrent clinicopathologic indicators are insufficient to distinguish the small percentage of aggressive prostate cancer (PCa) from the vast majority of indolent disease at diagnosis, leading to overtreatment of PCa. A recent study reported and confirmed a strong association of PCaspecific mortality with somatic DNA copy number alterations (CNAs) in primary prostate tumors. If a sensitive, robust and lowcost method can be developed to measure these CNAs in biopsy specimens, it may help to stratify patients for more appropriate management at the time of diagnosis; aggressive treatment or active surveillance for patients with or without these CNAs, respectively. A study on the association of somatic DNA copy number alterations (CNAs) in prostate tumors with lethal prostate cancer (PCa) by our collaborative group of Wake Forest University School of Medicine, the Brady Urological Institute of Johns Hopkins Medical Institutions, and the Karolinska Institute of Sweden was recently published in Cancer. Shortly after, two abstracts on the association of RNA expression of two different panels of genes with progression of PCa were presented by investigators from Mayo Clinic and University of California at San Francisco, respectively, in the 2013 American Urology Association Annual meeting. These studies all focused on the prognosis of PCa and received great attention in the scientific and clinical communities as well as in public, as evidenced by the news coverage. The excitement surrounding these studies is not surprising because distinguishing aggressive from indolent forms of PCa is probably the most important clinical task in managing and treating this heterogeneous disease. Most prostate tumors grow so slowly that they may never threaten a man’s life; however, ,15% are lethal if not treated appropriately. Currently used clinical predictors such as Gleason score and tumor stages are useful but insufficient to discriminate between the two types of PCa at the time of diagnosis. This inability leads to unnecessary and intensive treatment of many PCa patients, reducing their quality of life, and incurring financial burden to patients, families and society. Novel biomarkers are urgently needed to better identify aggressive PCa at the time of diagnosis for selection of treatment strategy; a choice of active surveillance for indolent PCa or intensive treatment for aggressive PCa. In this perspective piece, we highlight the key points of our Cancer paper on the association of CNAs with lethal PCa, discuss their advantages as markers for lethal PCa and describe the challenges for translating the genomic findings to clinics.