Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: A secondary analysis of the PR-7 trial of intermittent versus continuous ADT - Abstract

PURPOSE: Three small retrospective studies have suggested that patients undergoing continuous androgen deprivation (CAD) have superior survival and time to progression if lower castrate levels of testosterone (< 0.7 nmol/L) are achieved. Evidence from prospective large studies has been lacking.

PATIENTS AND METHODS: The PR-7 study randomly assigned patients experiencing biochemical failure after radiation therapy or surgery plus radiation therapy to CAD or intermittent androgen deprivation. The relationship between testosterone levels in the first year and cause-specific survival (CSS) and time to androgen-independent progression in men in the CAD arm was evaluated using Cox regression.

RESULTS: There was a significant difference in CSS (P = .015) and time to hormone resistance (P = .02) among those who had first-year minimum nadir testosterone ≤ 0.7, > 0.7 to ≤ 1.7, and ≥ 1.7 nmol/L. Patients with first-year nadir testosterone consistently > 0.7 nmol/L had significantly higher risks of dying as a result of disease (0.7 to 1.7 nmol/L: hazard ratio [HR], 2.08; 95% CI, 1.28 to 3.38; > 1.7 nmol/L: HR, 2.93; 95% CI, 0.70 to 12.30) and developing hormone resistance (0.7 to 1.7 nmol/L: HR, 1.62; 95% CI, 1.20 to 2.18; ≥ 1.7 nmol/L: HR, 1.90; 95% CI, 0.77 to 4.70). Maximum testosterone ≥ 1.7 nmol/L predicted for a higher risk of dying as a result of disease (P = .02).

CONCLUSION: Low nadir serum testosterone (ie, < 0.7 mmol/L) within the first year of androgen-deprivation therapy correlates with improved CSS and duration of response to androgen deprivation in men being treated for biochemical failure undergoing CAD.

Written by:
Klotz L, O'Callaghan C, Ding K, Toren P, Dearnaley D, Higano CS, Horwitz E, Malone S, Goldenberg L, Gospodarowicz M, Crook JM.   Are you the author?
Laurence Klotz, Sunnybrook Health Sciences Centre, University of Toronto; Mary Gospodarowicz, Princess Margaret Hospital, Toronto; Chris O'Callaghan and Keyue Ding, Queen's University, Kingston; Shawn Malone, Ottawa Regional Cancer Centre, Ottawa, Ontario; Paul Toren, Larry Goldenberg, and Juanita M. Crook, University of British Columbia, Vancouver, British Columbia, Canada; David Dearnaley, Royal Marsden Hospital, London, United Kingdom; Celestia S. Higano, Fox Chase Cancer Center, Philadelphia, PA; and Eric Horwitz, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA. .

Reference: J Clin Oncol. 2015 Mar 2. (Epub ahead of print)
doi: 10.1200/JCO.2014.58.2973


PubMed Abstract
PMID: 25732157