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

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

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

PloS one

2014

1905-07

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.

Humans; Male; Middle Aged; Aged; Treatment Outcome; Disease-Free Survival; *Nomograms; *Prostatectomy; Antineoplastic Agents/therapeutic use; Control Groups; Controlled Clinical Trials as Topic; Prostate/drug effects/pathology/surgery; Prostatic Neoplasms/*drug therapy/mortality/pathology/surgery; Neoplasm Recurrence; Chemotherapy; Adjuvant/*methods; Local/*drug therapy/mortality/pathology/surgery

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e85010–e85010

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