Improving power in PSA response analyses of metastatic castration-resistant prostate cancer trials

To determine how much an augmented analysis approach could improve the efficiency of prostate-specific antigen (PSA) response analyses in clinical practice. PSA response rates are commonly used outcome measures in metastatic castration-resistant prostate cancer (mCRPC) trial reports. PSA response is evaluated by comparing continuous PSA data (e.g., change from baseline) to a threshold (e.g., 50% reduction). Consequently, information in the continuous data is discarded. Recent papers have proposed an augmented approach that retains the conventional response rate, but employs the continuous data to improve precision of estimation.

A literature review identified published prostate cancer trials that included a waterfall plot of continuous PSA data. This continuous data was extracted to enable the conventional and augmented approaches to be compared.

Sixty-four articles, reporting results for 78 mCRPC treatment arms, were re-analysed. The median efficiency gain from using the augmented analysis, in terms of the implied increase to the sample size of the original study, was 103.2% (IQR [89.8,190.9%]).

Augmented PSA response analysis requires no additional data to be collected and can be performed easily using available software. It improves precision of estimation to a degree that is equivalent to a substantial sample size increase. The implication of this work is that prostate cancer trials using PSA response as a primary endpoint could be delivered with fewer participants and, therefore, more rapidly with reduced cost.