First off-time treatment prostate-specific antigen kinetics predicts survival in intermittent androgen deprivation for prostate cancer.
BACKGROUND
Prostate-specific antigen (PSA) doubling time is relying on an exponential kinetic pattern. This pattern has never been validated in the setting of intermittent androgen deprivation (IAD). Objective is to analyze the prognostic significance for PCa of recurrent patterns in PSA kinetics in patients undergoing IAD.


METHODS
A retrospective study was conducted on 377 patients treated with IAD. On-treatment period (ONTP) consisted of gonadotropin-releasing hormone agonist injections combined with oral androgen receptor antagonist. Off-treatment period (OFTP) began when PSA was lower than 4 ng/ml. ONTP resumed when PSA was higher than 20 ng/ml. PSA values of each OFTP were fitted with three basic patterns: exponential (PSA(t) = λ.e(αt)), linear (PSA(t) = a.t), and power law (PSA(t) = a.t(c)). Univariate and multivariate Cox regression model analyzed predictive factors for oncologic outcomes.


RESULTS
Only 45% of the analyzed OFTPs were exponential. Linear and power law PSA kinetics represented 7.5% and 7.7%, respectively. Remaining fraction of analyzed OFTPs (40%) exhibited complex kinetics. Exponential PSA kinetics during the first OFTP was significantly associated with worse oncologic outcome. The estimated 10-year cancer-specific survival (CSS) was 46% for exponential versus 80% for nonexponential PSA kinetics patterns. The corresponding 10-year probability of castration-resistant prostate cancer (CRPC) was 69% and 31% for the two patterns, respectively. Limitations include retrospective design and mixed indications for IAD.


CONCLUSIONS
PSA kinetic fitted with exponential pattern in approximately half of the OFTPs. First OFTP exponential PSA kinetic was associated with a shorter time to CRPC and worse CSS.
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
Rafael
R
Sanchez-Salas
Altran Research, Altran France, Velizy-Villacoublay, France.
Fabien
F
Olivier
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
Dominique
D
Prapotnich
Altran Research, Altran France, Velizy-Villacoublay, France.
José
J
Dancausa
Altran Research, Altran France, Velizy-Villacoublay, France.
Mehdi
M
Fhima
Altran Research, Altran France, Velizy-Villacoublay, France.
Stéphane
S
David
Urology Section, CEMIC and San Lazaro Foundation, Buenos Aires, Argentina.
Fernando P
FP
Secin
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
Alexandre
A
Ingels
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
Eric
E
Barret
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
Marc
M
Galiano
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
François
F
Rozet
Department of Urology, Institut Mutualiste Montsouris, Paris, France.
Xavier
X
Cathelineau
D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen
PSA kinetics; exponential pattern; intermittent androgen deprivation; predictors of survival; prostate cancer