ESTRO 38 Abstract book

S231 ESTRO 38

ESTRO 38 Monday 29 April

Teaching Lecture: Extreme hypofractionation in the treatment of localized prostate cancer

SP-0439 Extreme hypofractionation in the treatment of localized prostate cancer R. Valdagni 1 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiation Oncology 1, Milan, Italy Abstract text Over the past two decades, the radiation oncology community is being experiencing a major technical evolution in the radical irradiation (RT) of localized prostate cancer. Most significant improvements consist of the routine utilization of IMRT, of IGRT, also including active (e.g. electromagnetic transponders) or passive (e.g. gold fiducials markers) localization systems, of devices aimed to improve dosimetry in the perirectal space (e.g. rectal spacer and endorectal balloons) as well advances in prostate imaging. Such technical sophistication facilitates the definition, localization and monitoring of the tumor position, size and shape before and during treatment, together with the possibility of higher, targeted radiation doses to improve tumor control and decreased radiation exposure to normal tissues surrounding the tumor. Highly precise treatment delivery is leading to safely administer very conformal treatment at increased total doses in small volumes. This allows to overcome conventional fractionation (CF) and to routinely utilize moderate hypofractionation (M-HF) as well as to explore feasibility and safety of extreme hypofractionated (E-HF). The recently published guidelines on localized prostate cancer by ASTRO, ASCO, and AUA define M-HF as the daily fraction of 2.40-3.4 Gy and of ≥ 5 Gy for E-HF; this guideline underlines that, being HF a “spectrum” of fraction sizes and lacking a “universally accepted definition”, the above mentioned subdivision between M-HF and U-HF is “necessarily arbitrary” and pragmatically reflects most of the available clinically experience with M-HF and E-HF. The almost acquired evidence that the α/β ratio of prostate cancer is in the range of 1.5-2 Gy and that surrounding critical organs (rectum and bladder) tend to exhibit lower fractionation radiosensitivity (i.e. α/β range: 3-5 Gy), suggest the use of hypofractionated schemes to improve the therapeutic gain, exploiting high doses per fraction to achieve better tumor control probability. E-HF, particularly at single doses ≥ 8Gy, shows further radiobiological advantages with respect to C-F and M-HF, tumor microvasculature induced disruption appearing to be a significant ablative determinant which concurs in considerably increasing tumor cell death. Beside radiobiological and clinical considerations, E-HF implies additional advantages in terms of economical cost reduction and patients’ convenience (mainly but not only related to the possibility of gaining time), over CF- and M- HF, brachytherapy, proton irradiation and, because of non-invasiveness and of the evidence that radio-induced toxicities do not depend on patient’s age, over radical prostatectomy. To date, E-HF in localized prostate cancer has been used in low, intermediate and high risk tumors and appears very attractive for intermediate risk and potentially for high risk patients (the non malignant nature of GG I/GPS 3+3 strongly suggests to avoid overtreatment in low risk patients), showing good biochemical control and, with few exceptions, limited toxicities in the early- mid term follow up. However, the long survival of prostate cancer patients with localized disease and the present