Purpose:Implanted tissue spacers show great promise in reducing radiation dose to organs at risk (OAR) and/or permitting dose escalation to target volumes in IMRT plans. Dosimetric benefits have been demonstrated in a randomized study of such a device despite variations in plan optimization. The purpose of this analysis was to quantify the dosimetric effect of a tissue spacer using a validated prostate DVH prediction model trained with previous high‐quality clinical prostate plans.Methods:Imaging and treatment planning for men undergoing IMRT for localized stage T1‐T2 prostate cancer was performed before and after hydrogel spacer implantation between the prostate and anterior rectum. Pre‐ and post‐implant plans were independently optimized to satisfy dose‐volume criteria for rectum, bladder, and penile bulb. Image segmentation data were used to predict DVHs achievable using IMRT for rectum and bladder with institutionally‐validated model parameters [Medical Physics 39, 7446 (2012); doi: 10.1118/1.4761864]. Predicted and actual clinical DVHs (cDVH) for rectum were used to compare pre‐ and post‐implant plans.Results:101 pairs of plans from 5 clinical sites treating at least 14 spacer subjects each were analyzed. An average ± s.d. absolute reduction of 9.4 ± 6.5 % in V60 and 7.0 ± 4.6 % in V70 was seen for pDVH. Corresponding reductions in cDVH were 10.3 ± 6.2 % and 8.0 ± 4.3, respectively. Standard deviations of corresponding pDVH and cDVH values were similar. Correlation coefficients between predicted and actual Vx values were computed for pre‐implant, post‐implant, and pre‐post Vx differences. Correlations between pDVH and cDVH were significantly positive, but not uniform among clinical sites, suggesting differences in plan optimization.Conclusion:Predicted DVHs showed an absolute difference of nearly 10% in rectal volume receiving ≥ 60 Gy (50.4% relative reduction in V60) with use of peri‐rectal spacer, consistent with analysis of clincal pre‐ and post‐implant plans.This work was supported by a research grant from Augmenix, Inc.