Hypofractionation and Stereotactic Treatment: Clinical Data

Abstract

AbstractDuring the last decade, improved physical sparing of normal tissues with the most recent technologies and a better understanding of prostate cancer radiobiology has prompted a number of moderate as well as extreme hypofractionation trials using different treatment schedules with the aim of exploring the outcome and toxicity of shorter regimens. The hypofractionated regimes appear to be associated with excellent results and toxicity similar to that observed after conventional fractionation courses, in spite of the numerous variables relative to different distributions in the risk categories or androgen deprivation delivery in the trials. However, the relatively short follow-up and the single-arm nature of these reports do not permit any meaningful comparisons with the conventional regimes. Until now, six controlled randomized trials of moderate hypofractionation have been published. Notwithstanding the similar outcome and toxicity results between hypo and conventional fractionation, two of these studies used a 2D technique delivering total doses that are now considered insufficient and inconclusive for treating prostate cancer. In the most recent trial, reporting equivalent 2 year toxicity rates, the follow-up is still too short to evaluate the clinical outcome of the two schedules. The three remaining trials report similar biochemical outcomes between the short and standard regimes. Only one trial has a sufficiently long follow-up to confirm the equivalence of the two regimes in terms of biochemical, clinical local and distant failure, and overall and disease-specific survival. This trial also shows that in some subgroups of patients, i.e., those with a pretreatment PSA ≤ 20 ng/mL or with a T-stage ≥ 2c, hypofractionation may be better than conventional fractionation in terms of both local failure and disease-specific survival. These results suggest that moderate hypofractionation for prostate cancer does not increase treatment-related toxic effects or decrease efficacy, although they still need to be confirmed by trials with more patients. The premature results of extreme hypofractionation (or SBRT) studies, although associated with good treatment tolerance, excellent early biochemical outcomes and low late toxicity rates, do not lead to any firm conclusions on the clinical benefits of these regimes in comparison to escalated conventional dose fractionation. Given that a certain number of uncertainties exist in extrapolating biological effects to very large fraction size, the results of extreme hypofractionation need to be confirmed by appropriate randomized trials with a sufficiently long follow-up and accurate evaluation of long-term tolerance and toxicity.KeywordsProstate CancerAndrogen Deprivation TherapyStereotactic Body RadiotherapyConventional FractionationLate GradeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.