Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.
It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.
Department of Statistics, University of Akron, Akron, Ohio, United States of America ; Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Normal College, Guiyang, China ; Department of Family and Community Medicine, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
Zhenyu
Z
Jia
Division of Hematology-Oncology, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Michael B
MB
Lilly
College of Health, Human Services and Science, Ashford University, California, United States of America.
James A
JA
Koziol
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, California, United States of America.
Xin
X
Chen
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Xiao-Qin
XQ
Xia
AltheaDx Inc., San Diego, California, United States of America.
Yipeng
Y
Wang
Department of Urology, University of California Irvine, Irvine, California, United States of America.
Douglas
D
Skarecky
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, California, United States of America.
Manuel
M
Sutton
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, California, United States of America.
Anne
A
Sawyers
Department of Urology, Loma Linda University, Loma Linda, California, United States of America.
Herbert
H
Ruckle
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, California, United States of America.
Philip M
PM
Carpenter
Department of Pathology, University of California San Diego, La Jolla, California, United States of America.
Jessica
J
Wang-Rodriguez
Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Normal College, Guiyang, China.
Jun
J
Jiang
Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Normal College, Guiyang, China.
Mingsen
M
Deng
Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Normal College, Guiyang, China.
Cong
C
Pan
Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Normal College, Guiyang, China ; Department of Urology, Guizhou Provincial People's Hospital, Guizhou, China.
Jian-Guo
JG
Zhu
Department of Epidemiology, University of California Irvine, Irvine, California, United States of America.
Christine E
CE
McLaren
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Michael J
MJ
Gurley
Department of Statistics, University of Akron, Akron, Ohio, United States of America ; Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Chung
C
Lee
Department of Medicine, University of California Irvine, Irvine, California, United States of America ; Vaccine Research Institute of San Diego, San Diego, California, United States of America.
Michael
M
McClelland
Department of Urology, University of California Irvine, Irvine, California, United States of America.
Thomas
T
Ahlering
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America.
Michael W
MW
Kattan
Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, California, United States of America.
Dan
D
Mercola
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D035061:Control Groups; D018849:Controlled Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D049451:Nomograms; D011467:Prostate / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
D000970:Antineoplastic Agents