APG-990

available at http://www.ncbi.nlm.nih.gov/pubmed/25732157 Editorial Comment: The response to ADT is highly variable with regard to magnitude and duration. While all men inevitably progress to a state of castration resistance if they live long enough, some may take years to do so and others only months. It has been demonstrated previously that time to prostate specific antigen (PSA) nadir following institution of ADT correlates with duration of response/time to castration resistance. In this study the authors demonstrate that the actual first-year PSA nadir point in men with biochemical relapse placed on intermittent ADT is predictive of risk of prostate cancer death. Men with a nadir of less than 0.7 ng/dl showed the lowest risk of prostate cancer death and prolonged response to androgen deprivation. Each increasing PSA stratile, up to greater than 1.7 ng/ ml, demonstrated an increase in time to castration resistance and progression. In previous years such observations would be viewed as interesting but alternative treatment approaches were unavailable, thereby making the findings largely academic. With the current availability of a multitude of efficacious agents for advanced prostate cancer, earlier institution of second line therapy for men with incomplete or inadequate nadir may be a prudent consideration, given these observations. Samir S. Taneja, MD Suggested Reading Berruti A, Dogliotti L, Fasolis G et al: Changes in free and free-to-total prostate specific antigen after androgen deprivation or chemotherapy in patients with advanced prostate cancer. J Urol 1999; 161: 176. Re: Validation of an RNA Cell Cycle Progression Score for Predicting Death from Prostate Cancer in a Conservatively Managed Needle Biopsy Cohort J. Cuzick, S. Stone, G. Fisher, Z. H. Yang, B. V. North, D. M. Berney, L. Beltran, D. Greenberg, H. Moller, J. E. Reid, A. Gutin, J. S. Lanchbury, M. Brawer and P. Scardino Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine and Department of Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, and Cancer Epidemiology and Population Health, King’s College London, London, and National Cancer Registration Service (Eastern Office), Public Health England, Cambridge, United Kingdom, Myriad Genetics, Inc., Salt Lake City, Utah, and Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Br J Cancer 2015; 113: 382e389. doi: 10.1038/bjc.2015.223 0022-5347/16/1956-1779/0 THE JOURNAL OF UROLOGY 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. http://dx.doi.org/10.1016/j.juro.2016.03.056 Vol. 195, 1779-1783, June 2016 Printed in U.S.A. www.jurology.com j 1779 1780 PROSTATE CANCER Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26103570available at http://www.ncbi.nlm.nih.gov/pubmed/26103570 Editorial Comment: In this study the authors evaluate the ability of a biopsy derived cell cycle progression (CCP) score to predict prostate cancer death during long-term followup when combined with other conventional prognostic variables. CCP score refers to the results of a genetic panel analysis now commercially available as a test called Prolaris . CCP scores were determined from paraffin embedded biopsy samples of cases managed conservatively without radiation or surgery in the United Kingdom. CCP score was highly predictive of prostate cancer death, even when evaluated in a multivariate analysis including powerful predictive tools such as CAPRA (Cancer of the Prostate Risk Assessment) score. This cohort is distinct from earlier cohorts on which the Prolaris model was based in that it is more contemporary and comes at least from a prostate specific antigen (PSA) detection era. Earlier training sets on which the predictive risk of Prolaris is based were criticized as lacking face validity, given the much more advanced stage at diagnosis. However, in this group diagnosed between 2000 and 2003 face validity remains a concern. All patients were generally symptomatic at baseline, and treatments were not recorded for most after 6 months of study entry. It is noteworthy that 185 of 585 men had PSAs greater than 25 ng/ml at diagnosis, and these patients accounted for 54 of 100 prostate cancer deaths noted at a median of 9.64 years of followup. A total of 395 men had PSAs greater than 10 ng/ml. While CCP score independently predicted prostate cancer risk, with a rough doubling of risk with each doubling of CCP score, it is unclear how this predictive risk would perform in men diagnosed at much lower PSAs, for whom lead time to prostate cancer death is presumably greater. In other words, if the risk of death from prostate cancer is low for the entire cohort by 10 years (in this group it was 17%, which is greater than in contemporary PSA detected cohorts in the United States), it is unclear how much clinical impact such testing would have for the whole group. As these types of tests are generally applied to the lowest risk cohorts in determining need for treatment, this concern is magnified. This study validates the predictive ability of the test but offers little insight into clinical application in contemporary practice.