© 2011 THE AUTHORS 1086 BJU INTERNATIONAL © 2 0 11 B J U I N T E R N A T I O N A L | 1 0 8 , 1 0 8 6 – 1 0 9 2 | doi:10.1111/j.1464-410X.2010.10037,10541.x 2011 THE AUTHORS; BJU INTERNATIONAL 2011 BJU INTERNATIONAL Urological Oncology A RETROSPECTIVE STUDY EVALUATING AN ASSOCIATION BETWEEN AR-CAG REPEAT LENGTH AND TIME TO PROGRESSION AMONG A LARGE COHORT OF PROSTATE CANCER PATIENTS RECEIVING ANDROGEN DEPRIVATION THERAPY MISRA ET AL. Germline CAG repeat length of the androgen receptor and time to progression in patients with prostate cancer treated with androgen deprivation therapy Dipika Misra, Wanling Xie*, Meredith M. Regan*, Robert W. Ross † , Gwo-shu Lee † , Doris Germain, Philip W. Kantoff † and William K. Oh Division of Hematology and Medical Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, Departments of *Biostatistics and Computational Biology and † Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Accepted for publication 1 October 2010 RESULTS • There was no significant correlation between differences in the AR-CAG repeat lengths and TTP or overall survival in patients with prostate cancer receiving ADT. • AR-CAG repeat lengths did not significantly correlate with age, prostate- specific antigen (PSA), Gleason score or clinical stage at diagnosis. • In patients with metastatic disease, longer AR-CAG repeat lengths (>23 vs ≤23) were associated with a longer TTP on ADT, but this finding was of borderline significance (median TTP 18.3 vs 15.5 months, P = 0.09; adjusted HR = 0.76, 95% confidence interval = 0.54–1.09). CONCLUSIONS • This is the largest published study to date investigating the association of germline AR-CAG repeat lengths and efficacy of ADT in prostate cancer. • Germline AR-CAG repeat lengths do not predict response to ADT. KEYWORDS androgen receptor, prostate cancer, androgen deprivation therapy, polymorphisms What’s known on the subject? and What does the study add? Germline CAG repeat polymorphisms in the androgen receptor (AR-CAG) have been shown to influence the activity of the androgen receptor, but there has been conflicting data from small retrospective studies evaluating the effect of CAG repeat polymorphisms on response to ADT. This is the largest published study to date investigating the association of germline AR- CAG repeat lengths and efficacy of ADT in prostate cancer. Germline AR-CAG repeat lengths do not predict response to ADT. Study Type – Prognosis (retrospective cohort) Level of Evidence 2b OBJECTIVES • Germline CAG repeat polymorphisms in the androgen receptor (AR-CAG) have been shown to influence the activity of the AR. • The purpose of the present study was to determine if AR-CAG repeat length correlates with time to progression on androgen deprivation therapy (ADT). PATIENTS AND METHODS • Germline AR-CAG repeat lengths were determined in a cohort of 480 patients with recurrent or metastatic prostate cancer treated at a single tertiary care institution and correlated to time to progression (TTP) and overall survival. INTRODUCTION Although most patients with advanced prostate cancer respond to initial androgen deprivation therapy (ADT), they can have widely variable durations of response. Clinical factors such as Gleason score at diagnosis and serum PSA at time of ADT initiation can help to predict response to ADT; however, more accurate predictive markers are needed to determine the efficacy of ADT [1]. The androgen receptor (AR) plays a pivotal role in prostate cancer, including its progression from a hormone-sensitive to castration- resistant state, and factors that modify the function of AR could also influence individual patient responses to ADT. The N-terminus of the AR contains the transcriptional activation domain as well as a polymorphic CAG repeat encoding polyglutamine (AR-CAG) [2]. Several case–control studies have shown that a shorter number of CAG repeats in the AR correlate with a younger age of onset and more aggressive form of prostate cancer, and in vitro studies have shown that shorter CAG repeat lengths enhance transactivation and downstream signalling of AR [3–7]. BJUI BJU INTERNATIONAL