Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up.
BACKGROUND
Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization.


OBJECTIVE
Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences.


METHODS
EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients.


METHODS
Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival.


CONCLUSIONS
After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085).


CONCLUSIONS
This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.
Department of Urology, Inselspital, Bern, Switzerland. Electronic address: urs.studer@insel.ch.
Urs E
UE
Studer
St. James Hospital, Department of Urology, Leeds, UK.
Peter
P
Whelan
Department of Urology, Rudolfstiftung Hospital, Vienna, Austria.
Florian
F
Wimpissinger
Department of Urology, Damiaan Ziekenhuis, Oostende, Belgium.
Jacques
J
Casselman
Department of Urology, Academisch Medisch Centrum, Amsterdam, The Netherlands.
Theo M
TM
de Reijke
Department of Urology, University Hospital of Zürich, Zürich, Switzerland.
Hartmut
H
Knönagel
Department of Urology, Krankenhaus Barmherzige Schwestern, Linz, Austria.
Wolfgang
W
Loidl
Department of Urology, Hospital Nuestra Senora Del Pino, Las Palmas, Spain.
Santiago
S
Isorna
Mid Yorkshire NHS Trust, Department of Urology, Pinderfields Hospital, Wakefield, UK.
Subramanian K
SK
Sundaram
EORTC Headquarters, Department of Statistics, Brussels, Belgium.
Laurence
L
Collette
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D004334:Drug Administration Schedule; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009919:Orchiectomy / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000726:Androgen Antagonists
Androgen deprivation; Deferred treatment; Prostate cancer; Surrogate; Survival