In MR only radiation therapy planning, generation of the tissue specific HU map directly from the MRI would eliminate the need of CT image acquisition and may improve radiation therapy planning. The aim of this work is to generate and validate substitute CT (sCT) scans generated from standard T2 weighted MR pelvic scans in prostate radiation therapy dose planning. A Siemens Skyra 3T MRI scanner with laser bridge, flat couch and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole pelvis MRI (1.6 mm 3D isotropic T2w SPACE sequence) was acquired. Patients received a routine planning CT scan. Co-registered whole pelvis CT and T2w MRI pairs were used as training images. Advanced tissue specific non-linear regression models to predict HU for the fat, muscle, bladder and air were created from co-registered CT-MRI image pairs. On a test case T2w MRI, the bones and bladder were automatically segmented using a novel statistical shape and appearance model, while other soft tissues were separated using an Expectation-Maximization based clustering model. The CT bone in the training database that was most 'similar' to the segmented bone was then transformed with deformable registration to create the sCT component of the test case T2w MRI bone tissue. Predictions for the bone, air and soft tissue from the separate regression models were successively combined to generate a whole pelvis sCT. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same IMRT dose plan was found to be [Formula: see text] (mean ± standard deviation) for 39 patients. The 3D Gamma pass rate was [Formula: see text] (2 mm/2%). The novel hybrid model is computationally efficient, generating an sCT in 20 min from standard T2w images for prostate cancer radiation therapy dose planning and DRR generation.