Hypofractionated Radiotherapy for Localized Prostate Cancer: A Challenging Accelerated Hypofractionated Radiotherapy

Conventionally fractionated (CF) external-beam radiation therapy (1.8-2.0 Gy/fraction) is an established treatment modality for localized prostate cancer. Emerging evidence suggests that the alpha/beta ratio for prostate cancer is as low as 1.5, which has prompted investigators to explore hypofractionated (HF) radiation therapy. We reviewed the current status of hypofractionation and found that the accumulated outcomes reveal that dose escalation by moderate (2.5-4 Gy/fraction) hypofractionation (mHF) results in a better early biochemical outcome with acceptable complication rates, although there exist no marked advantages, other than the convenience of short treatment periods. Recently, hypofractionated external-beam radiotherapy has been challenged by accelerated hypofractionation (AHF), i.e., stereotactic body irradiation, particle therapy, and a high-doserate brachytherapy, using 5-10 Gy/fraction with a precise dose distribution and shorter treatment periods. Five-year biochemical control rates improved to >90%, even for high-risk groups, with a higher dose delivery using a safer technology. The overall survival rate reached nearly 100% at 5 years and was unaffected by prostate cancer, particularly in patients aged >80 years. Therefore, if maintaining the quality of life is the main purpose, short-term treatment is an attractive option from the socioeconomic perspective. Furthermore, CF and mHF regimens use equivalent doses at 2 Gy per fraction (EQD2) of 62-84 Gy, whereas AHF uses a higher EQD2 of 85 to 135 Gy if an alpha/beta ratio of 1.5 is applied. In the preliminary phase, AHF has theoretical advantages that not only reduce the treatment period but also potentially improve BC, particularly in high-risk groups using a higher EQD2.