Deriving Prostate Alpha-Beta Ratio Using Carefully Matched Groups, Long Follow-Up and the Phoenix Definition of Biochemical Failure

Abstract

Prior studies have derived low values of alpha-beta ratio (a/ß) for prostate cancer of approximately 1-2 Gy. These studies used poorly matched groups, differing definitions of biochemical failure, and insufficient follow-up. National Comprehensive Cancer Network low- or low-intermediate risk prostate cancer patients, treated with external beam radiotherapy or permanent prostate brachytherapy, were matched for prostate-specific antigen, Gleason score, T-stage, percentage of positive cores, androgen deprivation therapy, and era, yielding 118 patient pairs. The Phoenix definition of biochemical failure was used. The best-fitting value for a/ß was found for up to 90-month follow-up using maximum likelihood analysis, and the 95% confidence interval using the profile likelihood method. Linear quadratic formalism was applied with the radiobiological parameters of relative biological effectiveness = 1.0, potential doubling time = 45 days, and repair half-time = 1 hour. Bootstrap analysis was performed to estimate uncertainties in outcomes, and hence in a/ß. Sensitivity analysis was performed by varying the values of the radiobiological parameters to extreme values. The value of a/ß best fitting the outcomes data was >30 Gy, with lower 95% confidence limit of 5.2 Gy. This was confirmed on bootstrap analysis. Varying parameters to extreme values still yielded best-fit a/ß of >30 Gy, although the lower 95% confidence interval limit was reduced to 0.6 Gy. Using carefully matched groups, long follow-up, the Phoenix definition of biochemical failure, and well-established statistical methods, the best estimate of a/ß for low and low-tier intermediate-risk prostate cancer is likely to be higher than that of normal tissues, although a low value cannot be excluded.