Prostate cancer has been typically treated with a total radiation dose of 74-80 Gy administered in 2 Gy fractions. However, about 20% of patients suffer biochemical recurrence. Hypofractionated treatments may have a positive effect on tumour control. Nevertheless, the choice of an optimal personalised therapy is still compromised by the limited knowledge of the response of patients to high irradiation fractions. The purposes of this work were i) to predict biochemical recurrence after standard fractionation using our previously developed mechanistic model and ii) to explore the impact of hypofractionated treatments for patients who suffered biochemical failure. A cohort of 279 patients with localised prostate adenocarcinoma was used. Analogous virtual tissues were built from pre-treatment MRIs. The prescribed standard irradiation schedules were simulated using the mechanistic model. Biochemical recurrence was predicted from the in silico number of tumour cells at the end of treatment (AUC = 0.68). Then, alternative 2.5 and 3 Gy fractionations were simulated for patients who suffered biochemical recurrence. Significantly lower numbers of tumour cells at the end of treatment were obtained after these hypofractionated schedules. Significant decreases in total doses assuring tumour control were also observed for these patients (median of -10.3 and -14.0 Gy for 2.5 and 3 Gy fractionations, respectively). © 2022 IEEE.