Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group.
OBJECTIVE
To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone.


METHODS
A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data.


RESULTS
The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or "no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group.


CONCLUSIONS
PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.
Scher
Howard I
HI
Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. byczekb@mskcc.org
Halabi
Susan
S
Tannock
Ian
I
Morris
Michael
M
Sternberg
Cora N
CN
Carducci
Michael A
MA
Eisenberger
Mario A
MA
Higano
Celestia
C
Bubley
Glenn J
GJ
Dreicer
Robert
R
Petrylak
Daniel
D
Kantoff
Philip
P
Basch
Ethan
E
Kelly
William Kevin
WK
Figg
William D
WD
Small
Eric J
EJ
Beer
Tomasz M
TM
Wilding
George
G
Martin
Alison
A
Hussain
Maha
M
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology* / Q000628:therapy; D002986:Clinical Trials as Topic / Q000592:standards*; D018450:Disease Progression; D023381:Endpoint Determination; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care / Q000592:standards; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy; D012107:Research Design / Q000592:standards*; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
D013739:Testosterone; D017430:Prostate-Specific Antigen