Automating prostate radiotherapy treatment planning is dosimetrically complex, particularly for extreme hypofractionated regimens. In this study, we introduce Dose-PlanNet, a physics-guided 3D deep learning architecture designed to predict dose distributions.

This model's performance was evaluated on a cohort of patients treated in a prospective trial where two different dose fractionation regimens were employed. Dose-PlanNet achieved comparable target coverage ($D_{95}$), though statistical analysis revealed a marginal reduction in target homogeneity ($p<0.001$) offset.

However the model achieved statistically significant improvements in high-dose organ-at-risk sparing ($p<0.001$). When evaluated against strict Prospective Randomized protocol volumetric constraints, automated plans met prespecified clinical acceptance criteria in $11$ out of $14$ Moderate Hypofraction Arm plans and $9$ out of $12$ Stereotactic Body Radiation Therapy Arm plans.

This pipeline demonstrates that physics-informed deep learning can accelerate radiotherapy workflows while safely maintaining the stringent dosimetric quality required for high-precision clinical deployment.