Biological optimization of the dose in prostate cancer

Radiotherapy is one of the therapeutic options for nonmetastatic prostate carcinoma. Its outcomes seem superior to simply "wait-and-see" and comparable with those of radical prostatectomy. However, in locally advanced tumors the outcomes are not completely satisfactory. Therefore, in the last decades, numerous studies aimed at the optimization of therapy have been performed. The combination with hormonal therapy and dose escalation have allowed better clinical results. The effect of adjuvant hormonal therapy is well evident especially in phase III studies where the improvement both in biochemical relapse-free survival, cause-specific and overall survival, was documented. As for the effect of dose-escalation, at present, the improvement is limited to the biochemical disease-free survival, when considering the randomized studies. Both strategies seem unnecessary in low-risk patients while the advantages are evident in patients with intermediate-high-risk disease. In case of intermediate risk, dose escalation seems particularly effective while in high risk disease adjuvant hormonal therapy seems more advantageous. The role of dose escalation in this category is discussed, considering that many patients have no more a localized disease. The possibility of further improved clinical outcomes based on the combination of the two strategies is uncertain. Non conventional fractionations and hypofractionation in particular are still under experimentation and their utility has not been established as yet.