BackgroundThree-dimensional ultrasound (3DUS) is an attractive option in image-guided radiotherapy (IGRT) for prostate cancer (PCa) patients. However, the potential factors influencing the accuracy of 3DUS in comparison with cone-beam CT (CBCT) in IGRT for PCa patients haven't been clearly identified.MethodsThe differences between US/US and CBCT/CT registrations were analyzed over 586 and 580 sessions for 24 and 25 PCa patients treated with or without pelvic lymph node irradiation, respectively. The clinical factors that may influence registration differences were also evaluated.ResultsThe average discrepancies between US/US and CBCT/CT registrations were-0.285.28mm, -0.16 +/- 3.48mm, and-0.47 +/- 4.31mm in the superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions, respectively. The discrepancies were respectively less than 5mm longitudinally, laterally, and vertically in 64.4 and 70.1%, 84.9 and 89.2%, and 75.9 and 79.1% of the patients treated with or without pelvic lymph node irradiation, respectively. The registration differences were significantly smaller at least in one direction in patients younger than 70years, without pelvic lymph node irradiation, guided by transperineal ultrasonography and had a bladder volume smaller than 300mL.Conclusions p id=Par4 Age, irradiated regions, 3DUS modality, and bladder volume are important factors that may influence the differences between US/US and CBCT/CT registrations. 3DUS guidance is more feasible for younger PCa patients with a better control of bladder volume during the treatment and those who did not undergo pelvic lymph node irradiation.