Germline CAG repeat length of the androgen receptor and time to progression in patients with prostate cancer treated with androgen deprivation therapy.

Misra, Dipika; Xie, Wanling; Regan, Meredith M.; Ross, Robert W.; Lee, Gwo-shu; Germain, Doris; Kantoff, Philip W.; Oh, William K.

Study Type - Prognosis (retrospective cohort) Level of Evidence 2b 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. 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. 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.

PROSTATE cancer treatment; ANDROGEN drugs; GERM cells; DISEASE progression; PROSTATE-specific antigen; COHORT analysis

BJU International, 2011, Vol 108, Issue 7, p1086

1464-4096

Academic Journal

10.1111/j.1464-410X.2010.10037.x