Duration of androgen suppression in the treatment of prostate cancer.
BACKGROUND
The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer.


METHODS
We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429.


RESULTS
A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes.


CONCLUSIONS
The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)
Bolla
Michel
M
Centre Hospitalier Régional Universitaire de Grenoble, Grenoble, France. mbolla@chu-grenoble.fr
de Reijke
Theodorus M
TM
Van Tienhoven
Geertjan
G
Van den Bergh
Alphonsus C M
AC
Oddens
Jorg
J
Poortmans
Philip M P
PM
Gez
Eliahu
E
Kil
Paul
P
Akdas
Atif
A
Soete
Guy
G
Kariakine
Oleg
O
van der Steen-Banasik
Elsbietha M
EM
Musat
Elena
E
Piérart
Marianne
M
Mauer
Murielle E
ME
Collette
Laurence
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005485:Flutamide / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006331:Heart Diseases / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D011788:Quality of Life; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure
D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide; C053541:bicalutamide