Purpose To estimate the ratio α/β of Prostate Cancer from the effect of dose of radiation on the long term rise of prostate specific antigen (PSA). Materials and methods Repeated measures of PSA from 5,093 patients treated for localized prostate cancer by external beam radiation therapy (EBRT) were analysed. Patients came from 6 large cohorts. A biphasic linear mixed model described the post-treatment evolution of PSA. The effect of the radiation dose schedule on the long term rate of rise of PSA was estimated from the model. The model adjusted for standard prognostic factors (T-stage, initial PSA and Gleason) and cohort specific effects. Results Adjusted for other factors, total dose of EBRT and sum of squared doses per fraction were associated with long term rate of change of PSA (respectively p=0.0017 and p=0.0003), an increase of each being associated with a lower rate of rise. The ratio α/β was estimated at 1.55 Gy with 95% confidence interval [0.46;4.52]. This estimate was robust to adjustment of the linear mixed model but varied according to which cohorts were included, especially the one bringing hypofractioned schemes. Conclusions Using more than 5,000 patients treated by EBRT and a method that accounts for all the repeated measures of PSA after end of treatment rather than only the time of biochemical recurrence, a very low and precise value for α/β was estimated. This result favors hypofractionated radiation therapy that could better control the tumor with a reduced late toxicity. However outcome data from EBRT studies using higher doses per fraction are still needed to validate this result.

IBF is the single most robust prognostic factor for PCM following RT without androgen deprivation therapy. This external validation demonstrates that patients and clinicians can use this information to make decisions about subsequent treatments.