PURPOSE: To assess the magnitude of dosimetric reductions of a focal and ultra-focal high-doserate (HDR) prostate brachytherapy treatment strategy relative to standard whole gland (WG) treatment. METHODS AND MATERIALS: HDR brachytherapy plans for five patients treated with WG HDR monotherapy were optimized to assess different treatment strategies. Plans were generated to treat the hemigland (HG), one-third gland (1/3G), and one-sixth gland (1/6G), as well as to assess treating the WG with a boost to one of those sub-volumes (WG þ HG, WG þ 1/3G, WG þ 1/6G). Dosimetric parameters analyzed included Target D90%, V100%, V150%, Bladder (B), Rectal (R), Urethral (U) D0.1, 1 and 2cc, Urethral V75%, and the V50% to the contralateral HG. Two-tailed t tests were used for comparison of means, and p-values less than 0.05 were considered statistically significant. RESULTS: Target objectives (D90 O 100% and V100 O 97%) were met in all cases. Significant organs at risk dose reductions were achieved for all approaches compared with WG plans. 1/6G vs WG plans resulted in the greatest reduction in dose with a mean bladder D2cc 24.7 vs 64.8%, rectal D2cc 32.8 vs 65.3%, urethral D1cc 52.1 vs 103.8%, and V75 14.5 vs 75% ( p ! 0.05 for all comparisons). CONCLUSION: Significant dose reductions to organs at risk can be achieved using HDR focal brachytherapy. The magnitude of the reductions achievable with treating progressively smaller sub-volumes suggests the potential to reduce morbidity, but the clinical impact on morbidity and tumor control remain to be investigated. Ó