New Expert Guidance on EBRT in Men with Early-Stage Prostate Cancer

November 5, 2018

Oncologists now have some clarification on the use of moderate hypofractionation and ultrahypofractionation from ASTRO, ASCO, and the AUA.

Oncologists treating early-stage prostate cancer patients with external beam radiation therapy (EBRT) recently received some clarification regarding the use of moderate hypofractionation and ultrahypofractionation. The evidence-based guidelines, based on recent clinical evidence regarding oncologic outcomes, toxicity, and quality of life, were published online in the Journal of Clinical Oncology.

“Although many of us have been using some form of hypofractionated intensity-modulated radiotherapy for a while, there hasn’t been [a] consensus regarding who is an appropriate candidate for this treatment and what is the best dose/fractionation scheme to use. This guideline answers these questions,” Eric Horwitz, MD, FABS, FASTRO, chair of radiation oncology at Fox Chase Cancer Center in Philadelphia, told Cancer Network.

Hypofractionated radiation shortens treatment duration, which potentially improves resource utilization and results in cost savings, according to the new guideline, which was developed by a panel of experts from the American Society for Radiation Oncology (ASTRO), the American Society of Clinical Oncology (ASCO), and the American Urological Association (AUA). 

“In 2016–2017, three high-quality randomized hypofractionation clinical trials from North America and the UK involving more than 4,000 men were published. These trials demonstrated that shorter, moderately hypofractionated schedules of radiation were equivalent to longer, 8-to-9 week approaches. There was equivalence in cancer control, as well as equivalent and highly tolerable side effects profiles,” Howard Sandler, MD, a chair and professor of radiation oncology at Cedars-Sinai Medical Center in Los Angeles and co-chair of the guideline panel, told Cancer Network.

The recommendations apply to men who require or prefer treatment instead of surveillance and have opted for EBRT instead of radical prostatectomy, brachytherapy, or other treatment options for localized prostate cancer. For men who have opted for EBRT, moderate hypofractionation (fraction size of 240 to 340 centigray [cGy]) should be offered as an alternative to conventional fractionation (180 to 200 cGy), regardless of cancer risk group, patient age, comorbidity, anatomy, or baseline urinary function, according to the guideline.

The suggested regimens for moderate hypofractionation include the two schedules used with the largest number of patients in randomized clinical trials. These include 6,000 cGy delivered in 20 fractions of 300 cGy over 4 weeks, or 7,000 cGy delivered in 28 fractions of 250 cGy over 5.5 weeks.

Ultrahypofractionation (≥ 500 cGy) guidance varies by prostate cancer risk. The guideline calls for low-risk patients to be offered ultrahypofractionation as an alternative to conventional fractionation. For intermediate-risk disease, the guideline recommends offering ultrahypofractionation; however, the expert panel strongly encourages treating these patients as part of a clinical trial or multi-institutional registry. For high-risk disease, the panel does not suggest offering ultrahypofractionation outside of a trial or registry.

Suggested regimens for ultrahypofractionation include the two schedules used most commonly in published studies. These include 3,500 cGy in 5 fractions of 700 cGy, or 3,625 cGy in 5 fractions of 725 cGy. For 5-fraction regimens, the expert panel recommends against total radiation doses larger than 3,625 cGy outside of clinical trials or registries.

To develop this guideline, a 16-member expert panel of clinicians, researchers, and a patient advocate reviewed studies published from December 2001 through March 2017. A total of 61 articles, including 4 large prospective randomized clinical trials with more than 6,000 patients, were evaluated.