We evaluated the feasibility of using the kinetic of diffusion-weighted MRI (DWI) and the normalized apparent coefficient diffusion (ADC) map value as an early biomarker in patients treated by external beam radiotherapy (EBRT). Twelve patients were included within the frame of a multicenter phase II trial and treated for intermediate risk prostate cancer (PCa). Multiparametric MRI was performed before treatment (M0) and every 6 months until M24. Association between nADC and PSA or PSA kinetic was evaluated using the test of nullity of the Spearman correlation coefficient. The median rates of PSA at the time of diagnosis, two years and four years after EBRT were 9.29 ng/ml (range from 5.26 to 17.67), 0.68 ng/ml (0.07-2.7), 0.47 ng/ml (0.09-1.39), respectively. Median nADC increased from 1.14 × 10-3 mm2/s to 1.59 × 10-3 mm2/s between M0 and M24. Only one patient presented a decrease of nADC (1.35 × 10-3 mm2/s and 1.11 × 10-3 mm2/s at M0 and M12 respectively). The increase in nADC at M6 was correlated with PSA decrease at M18, M24 and M30 (p < 0.05). The increase in nADc at M12 was correlated with PSA decrease at M36 (p = 0.019). Early nADC variation were correlated with late PSA decrease for patients with PCa treated by EBRT.