Time to biochemical failure and prostate-specific antigen doubling time as surrogates for prostate cancer-specific...

Area of Science:

• Oncology
• Clinical Trials
• Biostatistics

Background:

• Established surrogate endpoints for prostate cancer-specific mortality after curative treatment are lacking.
• This study investigated time to biochemical failure (TTBF) and prostate-specific antigen doubling time (PSADT) as potential surrogate endpoints.

Purpose of the Study:

• To evaluate TTBF and PSADT as surrogate endpoints for prostate cancer-specific mortality.
• To assess their ability to predict trial outcomes and meet established criteria for surrogate endpoints.

Main Methods:

• Utilized PSA and survival data from the TROG 96.01 trial involving 802 men with locally advanced prostate cancer.
• Patients received radiation alone or with 3 or 6 months of short-term androgen deprivation (STAD).
• Assessed surrogate candidates based on Prentice criteria and prediction of trial findings.

Main Results:

• Six months of STAD significantly reduced prostate cancer-specific mortality, while 3 months did not.
• PSADT met Prentice criteria, predicting trial findings with proportion of treatment effect ratios between 0.36 and 0.56.
• TTBF demonstrated superior prediction of trial findings and met Prentice criteria at multiple cutpoints, with ratios between 0.45 and 0.64.

Conclusions:

• TTBF and PSADT can serve as valuable surrogate endpoints for prostate cancer-specific mortality.
• These surrogate endpoints have the potential to significantly reduce follow-up periods in clinical trials.
• Further validation through multi-trial meta-analyses is recommended before widespread clinical adoption.