Alpha/beta (α/β) ratio for prostate cancer derived from external beam radiotherapy and brachytherapy boost

There is disagreement regarding the value of the α/β ratio for prostate cancer. Androgen deprivation therapy (ADT) may dominate the effects of dose fractionation on prostate-specific antigen (PSA) response and confound estimates of the α/β ratio. We estimate this ratio from combined data on external beam radiation therapy (EBRT) and brachytherapy (BT)-treated patients, providing a range of doses per fraction, while accounting for the effects of ADT.

We analyse data on 289 patients with local prostate cancer treated with EBRT (2 Gy per fraction) or EBRT plus one or two BT boosts of 10 Gy each. The timing of ADT was heterogeneous. We develop statistical models to estimate the α/β ratio based upon PSA measurements at 1 year as a surrogate for the surviving fraction of cancer cells as well as combined biochemical + clinical recurrence-free survival (bcRFS), controlling for ADT.

For the PSA-based end point, the α/β ratio estimate is 7.7 Gy [95% confidence interval (CI): 4.1 to 12.5]. Based on the bcRFS end point, the estimate is 18.0 Gy (95% CI: 8.2 to ∞).

Our model-based estimates of the α/β ratio, which account for the effects of ADT and other important confounders, are higher than some previous estimates.

Although dose inhomogeneities and other limitations may limit the scope of our findings, the data suggest caution regarding the assumptions of the α/β ratio for prostate cancer in some clinical environments.