External-beam radiation therapy (EBRT) is a standard treatment option for men with localized prostate cancer and confers long-term prostate cancer control outcomes equal to radical prostatectomy. Technologic advances in imaging and computing during the past 20 years have led to a number of innovations in prostate EBRT, which together have allowed for more precise delivery of escalated doses of radiation to the prostate. More recently, several clinical trials investigating hypofractionated EBRT—courses of treatment in which fewer, larger-dose fractions of radiation are delivered—have been completed.
With the results of these trials emerging, three oncology organizations created a task force to develop a guideline offering recommendations on the use of hypofractionated EBRT. The American Society for Radiation Oncology (ASTRO), ASCO, and the American Urological Association (AUA) worked together to conduct a systematic literature review on which the recommendations are based. The guideline was recently published in the Journal of Clinical Oncology.1
Scott Morgan, MD, MSc, FRCPC
Howard M. Sandler, MD, FASCO, FASTRO
In the following interview, guideline Co-Chairs Scott Morgan, MD, MSc, FRCPC, and Howard M. Sandler, MD, FASCO, FASTRO, offer their perspective on the importance of this therapy and how it improves patient care. Dr. Morgan is a radiation oncologist at The Ottawa Hospital Cancer Centre and Assistant Professor, Radiation Oncology, at the University of Ottawa. Dr. Sandler is Ronald H. Bloom Family Chair in Cancer Therapeutics and Professor and Chairman of Radiation Oncology at the Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles.
Moderate Hypofractionation vs Ultrahypofractionation
How do you differentiate between moderate hypofractionation and ultrahypofractionation as treatment techniques?
In clinical practice, two fairly distinct approaches to hypofractionation have arisen, and the guideline distinguishes between them. “Moderate hypofractionation” is defined in the guideline as a fraction size between 2.4 Gy and 3.4 Gy. Two common moderately hypofractionated regimens are 60 Gy in 20 fractions delivered over 4 weeks or 70 Gy in 28 fractions delivered over 5.5 weeks.
“Ultrahypofractionation,” on the other hand, is defined as a fraction size of at least 5 Gy. It is also referred to as “extreme hypofractionation,” “stereotactic body radiation therapy,” and “stereotactic ablative radiation therapy.” A typical ultrahypofractionated regimen consists of 5 fractions of 7.25 Gy given on alternating days over about 2 weeks, for a total dose of 36.25 Gy. So, the difference between the two approaches is in degree rather than in kind.
What are the key takeaways of the guideline?
The main takeaway is the 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 and is based on the results of several large-scale randomized trials that enrolled thousands of men with localized prostate cancer over the past several years.2-5
How will the practice-changing recommendations benefit patients most?
The main benefit for patients is that, compared with conventional fractionation, hypofractionation is as effective, no more toxic over the long term, and substantially more convenient given its shorter treatment schedule. Conventionally fractionated regimens for localized prostate cancer extend over 7.5 to 9.0 weeks, whereas moderately hypofractionated schedules are 4.0 to 5.5 weeks. Therefore, the overall treatment time is roughly halved.
How can oncologists apply the recommendations in the clinic?
Based on the results of the completed trials and the guideline recommendations that they inform, moderate hypofractionation represents a new standard of care for the delivery of radiation therapy for localized prostate cancer. A large majority of patients with localized prostate cancer who choose EBRT as their primary treatment modality will now be appropriately treated with moderate hypofractionation. 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.
Although moderate hypofractionation is ready for routine use in the clinic, the task force adopted a more cautious view on the use of ultrahypofractionated 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 ongoing clinical trials evaluating this treatment approach. As the results from these trials emerge, the recommendations regarding ultrahypofractionation will likely be reviewed. ■
DISCLOSURE: For full disclosures of all task force members, visit www.jco.ascopubs.org.
1. Morgan SC, Hoffman K, Loblaw DA, et al: Hypofractionated radiation therapy for localized prostate cancer: An ASTRO, ASCO, and AUA evidence-based guideline. J Clin Oncol. October 11, 2018 (early release online).
2. Dearnaley D, Syndikus I, Mossop H, et al: Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CCHiP trial. Lancet Oncol 17:1047-1060, 2016.
3. Incrocci L, Wortel RC, Alemayehu WG, et al: Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer: Final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 17:1061-1069, 2016.
4. Lee WR, Dignam JJ, Amin MB, et al: Randomised phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol 34:2325-2332, 2016.
5. Catton CN, Lukka H, Gu CS, et al: Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer. J Clin Oncol 35:1884-1890, 2017.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 22, 2019. All rights reserved.