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Serum Androgen Normalization Kinetics & Factors Linked To Testosterone Reserve After Limited Androgen Deprivation Therapy

April 10, 2017

UroToday - How rapidly serum androgen levels fall after androgen-deprivation therapy (ADT) and recover between cycles for patients with prostate cancer (CaP) undergoing intermittent androgen suppression (IAS) is not well studied. Yet the information has clinical utility for both patient quality of life and cancer management. In the online version of the Journal of Urology, Dr. James Gulley from the National Cancer Institute and a multi-institutional group of investigators reported on androgen kinetics with ADT and variables that impact it.

Patient data was obtained from a phase III clinical trial of limited IAS in men with non-metastatic CaP who presented with a rising PSA following local therapy. In cycle I, 6 months of GnRH-A therapy was given followed by thalidomide or placebo. This was repeated in cycle 2, which began when the PSA increased to 5ng/ml or above. Testosterone (T) and dihydrotestosterone (DHT) were measured at study enrollment and regularly thereafter.

A total of 129 patients made up the study cohort. The primary endpoint was time to recovery of T to low (50-211ng/dl) and normal (>211ng/dl) levels. During cycle 1, median time to T normalization was 15.4 weeks. In men with an initial normal baseline T, it was 14.4 weeks compared to 31.3 weeks in patients with low baseline T. In those with a low baseline T, the median time to a T recovery to the low concentration (50-211ng/dl) was longer (14.5 weeks) compared to 10.7 weeks in men with a normal baseline T. The median patient age was 67 years. Overall, men 67 years and younger had a shorter time to serum T normalization than men older than 67 years. A low baseline T compounded this observation. The recovery of T following ADT was longer (12.8 weeks) if the PSA nadir was 20ng/ml or less, compared to 6.7 weeks if the PSA nadir was above 20ng/ml. In the multivariable analysis, only age and baseline DHT were significantly associated with the time of the T recovery to normal in cycle 1.

Time to T normalization was 18.3 weeks in cycle 2, which was 2.9 weeks longer than in cycle 1. Overall median time to an increase of T to low levels was 11.5 weeks, and again a low baseline T resulted in a longer time to serum T normalization. Thalidomide did not affect time to serum T normalization in either cycle. Prior radiotherapy was associated with a delay in the T increase to a low or normal concentration. As in cycle 1, a T nadir of 20ng/dl or less was associated with a longer time to recovery to a low or normal T level. In cycle 2 multivariable analysis, T, DHT, race and T nadir were significantly associated with the time affecting T recovery to normal. Thus, several variables including the baseline T reserve prior to ADT as manifested by age and baseline T levels impact the time to T recovery following ADT.

Gulley JL, Aragon-Ching JB, Steinberg SM, Hussain MH, Sartor O, Higano CS, Petrylak DP, Chatta GS, Arlen PM, Figg WD, Dahut WL
J Urol. 2008 Aug 16

UroToday Contributing Editor Christopher P. Evans, MD, FACS

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