Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline

Compared to most other solid tumors, prostate cancer appears to exhibit a greater sensitivity to radiation fraction size. This observation has spurred investigation of hypofractionated external beam radiation therapy (EBRT) in the management of localized prostate cancer. Eight randomized trials comparing moderately hypofractionated EBRT (defined as a daily fraction size between 240 cGy and 340 cGy) and conventionally fractionated EBRT (180-200 cGy daily) have been completed and, among these, the four largest trials reported efficacy results in 2016 and 2017. At the same time, use of ultra-hypofractionated EBRT (daily fraction size of at least 500 cGy), also referred to as stereotactic body radiation therapy (SBRT), has been observed to be increasing in routine clinical practice in the absence of randomized evidence. In this context, the American Society for Radiation Oncology, in collaboration with the American Society of Clinical Oncology and the American Urological Association, convened a task force to issue recommendations on the use of hypofractionated EBRT.

The completed randomized trials have shown consistently that, compared to conventional fractionation, moderate hypofractionation is as effective, no more toxic over the long term, and substantially more convenient given its shorter treatment schedule. (Conventionally fractionated regimens extend over 7½ to 9 weeks; moderately hypofractionated schedules, by contrast, are typically 4 to 5½ weeks.) These results have informed the guideline’s key recommendation, graded as “strong” and endorsed unanimously by the task force, that moderate hypofractionation should be offered to men with localized disease receiving prostate EBRT. This recommendation applies across all risk groups.

In short, moderate hypofractionation represents a new standard of care for the delivery of EBRT for localized prostate cancer. A large majority of patients with localized prostate cancer choosing EBRT as their primary treatment will now be appropriately treated with moderate hypofractionation and their overall treatment time will be roughly halved compared to the previous standard. It is only in a minority of clinical scenarios – for example, where the decision has been made to include the pelvic lymph nodes in the treatment volume – that the role for moderate hypofractionation requires further study.

While moderate hypofractionation is ready for routine use in the clinic, the task force has adopted a more cautious view on the use of ultra-hypofractionated EBRT at this time. Ultrahypofractionation is conditionally recommended as an option in low-risk and intermediate-risk disease, but the task force strongly recommends that patients in the latter group be offered participation in clinical trials or multi-institutional registries investigating this treatment approach. Several large-scale randomized trials evaluating ultra-hypofractionation are at various stages of completion. A 1200-patient Scandinavian trial, HYPO-RT-PC, reported very promising efficacy and toxicity results in abstract form earlier this year. NRG-GU005 is accruing patients across North America to a randomized comparison of a 5-fraction ultra-hypofractionated schedule and a 28-fraction moderately hypofractionated regimen. Finally, the similarly-designed PACE B trial, conducted in the United Kingdom and Canada, closed to accrual last year after meeting its goal of over 800 patients. As the results from these trials emerge, the ASTRO-ASCO-AUA recommendations regarding ultra-hypofractionation will likely be reviewed and updated.

Written By: Scott Morgan, MD, MSc, FRCPC, Co-Chair, ASTRO-ASCO-AUA Hypofractionated EBRT for Prostate Cancer Guideline Task Force, Division of Radiation Oncology, The Ottawa Hospital, Assistant Professor, University of Ottawa, Ottawa, Ontario, Canada

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