Hypofractioned radiotherapy in prostate cancer: is it the next step?

Abstract

There are many available options for prostate cancer treatment, including active surveillance, surgery, brachytherapy and external beam radiotherapy. Based on a radiobiological rationale, which considers the prostate tumor as a low α/β tumor, the use of higher and fewer fractions to prostate cancer external beam radiotherapy treatment has been proposed. Instead of the traditional fractions of 1.8–2.0 Gy per day, fractions higher than 2 Gy per day were the subject of a number of studies. In addition, new technologies such as intensity-modulated radiation therapy, image-guided radiation therapy, volumetric-modulated arch therapy and others have emerged as background for changing paradigms. Meanwhile, moderate and ultra-hypofractionation have been the subject of studies in recent years. Some moderate hypofractionation data from randomized controlled trials are ready to use, though other non-inferiority data are still lacking. The data on ultra-hypofractionation are still very new and require further evaluation to determine its long-term safety and efficacy.

Keywords::

• biochemical control
• hypofractionation
• IMRT
• prostate cancer
• radiotherapy
• toxicity

Financial & competing interests disclosure

The authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest in or with financial conflict concerning the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

This manuscript was reviewed by a professional science editor and by a native English-speaking copy editor to improve readability.

Key issues

• The α/β ratio indicates the sensitivity of a cell to alterations in fraction size.

• Rapidly proliferating cells are not very sensitive (higher α/β), whereas slowly proliferating cells are very sensitive to fraction sizes. This seems to be the case for prostate tumor cells (low α/β).

• Emerging technologies based on treatment planning (intensity-modulated radiation therapy, volumetric-modulated arch therapy) and image-guided treatment delivery (image-guided radiation therapy: Kv planar images; cone beam CT) enable new fractioning schemes (stereotactic body radiotherapy and hypofractioned radiotherapy).

• Moderate hypofractionation (2.4–4 Gy per fraction) is a potentially valuable regimen for the treatment of prostate patients, both due to patient convenience and to the benefits of potentially increasing the therapeutic ratio.

• Ready-to-use data from the trials used to test the superiority of moderate hypofractionation over conventional regimes are negative. It is not possible to conclude that these schemes are equivalent, only that they are different.

• Results of the non-inferiority comparison between moderate hypofractionation over conventional regimes will be available in the next few years and will be important to reveal whether moderate hypofractionation should be established as the standard regimen.

• Most research centers that tested moderate hypofractionation used modern radiotherapy techniques (at least conformal 3D planning or intensity-modulated radiation therapy) and some kind of image-guided radiation therapy such as cone beam CT or ultrasound.

• The use of ultra-hypofractionation requires further evaluation to determine its long-term safety and efficacy.