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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
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. laurence.klotz@sunnybrook.ca.
Laurence
L
Klotz
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.
Chris
C
O'Callaghan
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.
Keyue
K
Ding
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.
Paul
P
Toren
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.
David
D
Dearnaley
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.
Celestia S
CS
Higano
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.
Eric
E
Horwitz
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.
Shawn
S
Malone
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.
Larry
L
Goldenberg
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.
Mary
M
Gospodarowicz
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.
Juanita M
JM
Crook
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D016019:Survival Analysis; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
D000726:Androgen Antagonists; D013739:Testosterone