Moderate hypofractionated radiotherapy for localised prostate cancer: A new standard of care

Abstract

Radical radiotherapy is an effective treatment and standard of care for localised prostate cancer. Most conventionally treatment has been given with 1.8 to 2.0 Gy fractions to a dose of 74 to 79.2 Gy. Radiobiology insights have encouraged the exploration of hypofractionated schedules. Over 7000 patients have contributed to eight randomised controlled trials comparing conventional fractionation with modest hypofractionation using 2.4 to 3.4 Gy fractions. These studies have used both non-inferiority statistical designs aiming to define isoeffective and isotoxic moderate hypofractionated radiotherapy schedules as well as dose-escalated hypofractionated schedules intended to show improved disease control whilst maintaining a low level of late side effects. Long-term follow-up of over 10 years is now available from four of the studies. Patients with low-high risk disease have been studied treating with or without androgen-deprivation. Meta-analysis of individual patient data from seven available trials has been performed with median follow-up of 5 to 7 years. The studies of isoeffective moderate hypofractionated radiotherapy show that a dose of 60 Gy in 3 Gy fractions delivered over 4 weeks is non-inferior to doses of 74 Gy to 78 Gy in 2 Gy fractions delivered over 7.4 to 7.8 weeks with similar levels of disease control and survival. Low levels of late side effects were maintained using intensity-modulated radiotherapy techniques. In distinction trials using dose-escalated hypofractionated schedules have not increased effectiveness and have raised levels of late side effects. This may relate to very modest hypofractionation and treatment protraction. There is now adequate evidence for radiotherapy delivering 60 Gy in 20 fractions over 4 weeks to be the standard schedule for all patients with localised prostate cancer.