Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.
OBJECTIVE
To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA).


RESULTS



OBJECTIVE
A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population.


METHODS
The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed.


METHODS
Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation.


RESULTS
An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned.


METHODS
The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative.


CONCLUSIONS
Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.
Scher
Howard I
HI
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. scherh@mskcc.org
Eisenberger
Mario
M
D'Amico
Anthony V
AV
Halabi
Susan
S
Small
Eric J
EJ
Morris
Michael
M
Kattan
Michael W
MW
Roach
Mack
M
Kantoff
Philip
P
Pienta
Kenneth J
KJ
Carducci
Michael A
MA
Agus
David
D
Slovin
Susan F
SF
Heller
Glenn
G
Kelly
William Kevin
WK
Lange
Paul H
PH
Petrylak
Daniel
D
Berg
William
W
Higano
Celestra
C
Wilding
George
G
Moul
Judd W
JW
Partin
Alan N
AN
Logothetis
Christopher
C
Soule
Howard R
HR
D002986:Clinical Trials as Topic; D004608:Eligibility Determination; D006287:Health Planning Guidelines; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome; D014481:United States
D017430:Prostate-Specific Antigen