Relationships between times to testosterone and prostate-specific antigen rises during the first off-treatment interval of intermittent androgen deprivation are prognostic for castration resistance in men with nonmetastatic prostate cancer - Abstract

BACKGROUND: Intermittent androgen deprivation (IAD) represents an alternative to continuous AD with quality-of-life benefit and no evidence of inferior overall survival for nonmetastatic prostate cancer.

Early markers of prognosis for men treated with IAD have not been described.

PATIENTS AND METHODS: Men with nonmetastatic prostate cancer were treated with 9 months of leuprolide and flutamide followed by a variable off-treatment interval; AD was resumed when prostate specific antigen (PSA) reached a prespecified value (1 ng/mL, radical prostatectomy; 4 ng/mL, intact prostate). Cycles were repeated until castration resistance (marking the advent of castration-resistant prostate cancer [CRPC]), defined as 2 PSA rises with testosterone (T) ≤ 50 ng/dL. Kinetics and relationships of PSA and T levels were evaluated, with a focus on times to rise in each level, during the first off-treatment interval. Associations with CRPC and prostate cancer mortality were estimated using Cox proportional hazards models controlling for age and Gleason score.

RESULTS: Each 30-day increase in time to PSA rise was associated with a 21% reduction in the risk of developing CRPC (95% CI, 3%-36%; P = .02). Longer time (≥ 60 days) to PSA rise after rise to T > 50 ng/dL was associated with a 71% reduction in the risk of developing CRPC (95% CI, 92% reduction to 2% inflation; P = .05). Time to first T > 50 ng/dL and PSA doubling time were not prognostic for progression to CRPC. No time interval was prognostic for prostate cancer mortality.

CONCLUSION: During the first off-treatment interval of IAD, longer times to PSA rise overall and after T > 50 ng/dL were associated with reduced risk of developing CRPC.

Written by:
Kuo KF, Hunter-Merrill R, Gulati R, Hall SP, Gambol TE, Higano CS, Yu EY.   Are you the author?
Case Western Reserve University School of Medicine, Cleveland, OH; Fred Hutchinson Cancer Research Center, Biostatistics and Biomathematics Program, Public Health Sciences Division, Seattle, WA; University of Washington/Fred Hutchinson Cancer Research Center, Department of Medicine, Division of Oncology, Seattle, WA.  

Reference: Clin Genitourin Cancer. 2014 Aug 10. pii: S1558-7673(14)00175-X.
doi: 10.1016/j.clgc.2014.08.003

PubMed Abstract
PMID: 25242417 Prostate Cancer Section