TROG 03.06 and VCOG PR 01-03: The "Timing of androgen deprivation therapy in prostate cancer patients with a rising PSA (TOAD)" collaborative randomised phase III trial.

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Prostate) Cancer
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 5007)
Gillian M. Duchesne, Julie Bassett, Catherine D'Este, Mark Frydenberg, Leo Ledwich, Jeremy Laurence Millar, Roger L Milne, Rosemary Smith, Nigel Spry, Martin R. Stockler, Rodney Syme, Sandra Turner, Keen Hun Tai, Henry Woo, TROG & Cancer Council Victoria; Peter MacCallum Cancer Centre, East Melbourne, Australia; Cancer Epidemiology Centre, Cancer Council Victoria,, Melbourne, Australia; NCEPH, Australian National University, Canberra, Australia; Monash Health, Clayton, Australia; Consumer representative, Altona, Australia; Alfred Health, Melbourne Victoria, Australia; Cancer Council Victoria, Melbourne, Australia; Cancer Council Victoria Clinical Trials Office, Melbourne, Australia; Genesis Cancer Care, Perth, Australia; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia; Retired, Toorak, Australia; Westmead Hospital, Sydney, Australia; Westmead Private Hospital, Sydney, Australia

Abstract Disclosures


Background: This randomized, prospective phase III trial investigated if immediate intervention with androgen deprivation therapy (ADT) (Arm B) improved overall survival compared to delayed ADT introduction (Arm A) in prostate cancer patients with PSA relapse after definitive therapy, or in asymptomatic men not suitable for curative therapy at diagnosis. Methods: Eligible patients were randomised 1:1, and stratified by planned intermittent or continuous (I or C) ADT; treatment centre; prior therapy (prostatectomy or radiation therapy); relapse-free interval < or ≥ 2 years; and PSA doubling time of < or ≥ 10 months. The primary endpoint was unadjusted overall survival by intention-to-treat. Secondary endpoints were cancer specific survival, time-to-clinical progression, time-to-castration resistance, cancer- and treatment-related complications, and quality of life. Sample size calculations for 80% power, α level of 5%, and a 2-sided statistical test required 750 patients to show a 10% improvement in survival. Results: From September 2004 to July 2012, 293 patients were randomised (A: 151, B:142) with a median follow-up of 5.0 years. There were 46 deaths, 30 for Arm A (delayed) and 16 for Arm B (immediate). Overall survival (OS) (log rank unadjusted) was significantly higher in Arm B than Arm A (p = 0.047), with 6-year survival rates of 86% and 79% respectively. The hazard ratio (HR) for death from all causes for Arm B relative to Arm A (Cox adjusted regression analysis) was 0.54, 95% confidence interval (CI) 0.27,1.06, p = 0.07. Death from prostate cancer was reduced in Arm B (HR 0.50 CI 0.17,1.51, p = 0.22), as was death from other causes (HR 0.57 CI 0.31,1.05, p = 0.07), both non-significantly. Overt local and distant disease progression were significantly reduced in Arm B (HR 0.51 CI 0.34,0.76, p = 0.001; HR 0.54 CI 0.32,0.90, p = 0.018). There was no difference in the time to castrate resistance. In Arm A 34% of patients started ADT within 2 years, while 49% started later than 4 years on trial or had not yet commenced therapy. Conclusions: Overall survival and time to clinical progression were significantly improved for immediate versus delayed ADT. Clinical trial information: 12606000301561.