Generation of "virtual" control groups for single arm prostate cancer adjuvant trials

Zhenyu Jia, Michael B. Lilly, James A. Koziol, Xin Chen, Xiao Qin Xia, Yipeng Wang, Douglas Skarecky, Manuel Sutton, Anne Sawyers, Herbert Ruckle, Philip M. Carpenter, Jessica Wang-Rodriguez, Jun Jiang, Mingsen Deng, Cong Pan, Jian Guo Zhu, Christine E. McLaren, Michael J. Gurley, Chung Lee, Michael McClellandThomas Ahlering, Michael W. Kattan, Dan Mercola

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere85010
JournalPloS one
Volume9
Issue number1
DOIs
StatePublished - Jan 21 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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