Three prominent medical organizations have issued a new clinical guideline for physicians treating men with early-stage prostate cancer using external-beam radiation therapy (EBRT). Developed by a panel of experts from the American Society for Radiation Oncology (ASTRO), ASCO, and the American Urological Association (AUA), the new guideline recommends offering patients hypofractionated radiation therapy as an alternative to longer, conventional courses of radiation. ASTRO, ASCO, and AUA published the guideline in their respective journals, Practical Radiation Oncology,1 the Journal of Clinical Oncology,2 and The Journal of Urology.3
Conclusive evidence from several large, well-designed randomized trials now confirms that dose escalation can almost universally benefit men with early-stage prostate cancer who choose to manage their disease with external radiation.— Howard Sandler, MD, FASTRO, FASCO
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“Conclusive evidence from several large, well-designed randomized trials now confirms that dose escalation can almost universally benefit men with early-stage prostate cancer who choose to manage their disease with external radiation,” said Howard Sandler, MD, FASTRO, FASCO, Chair and Professor of Radiation Oncology at Cedars-Sinai Medical Center, Los Angeles, and Co-Chair of the guideline panel. “Significant advances in treatment planning and delivery have enabled oncologists to deliver more powerful, life-saving doses of radiation in fewer visits, and without compromising quality of life.”
EBRT is a standard definitive treatment option that confers outcomes equivalent to radical prostatectomy for men with localized prostate cancer, according to research by Hamdy et al in The New England Journal of Medicine.4 When EBRT is hypofractionated, patients receive larger radiation doses across fewer treatment sessions—typically completing treatment in 4 to 5 weeks, compared with 8 to 9 weeks for conventional radiation. Extremely hypofractionated courses—also known as ultrahypofractionation, stereotactic body radiation therapy. or stereotactic ablative radiation therapy—can be completed in as few as five treatments.
Key Guideline Recommendations
The recommendations apply to patients 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. Key recommendations follow:
For men who have opted for EBRT, moderate hypofractionation (240–340 cGy/fraction) should be offered as an alternative to conventional fractionation (180–200 cGy) regardless of cancer risk group, patient age, comorbidity, anatomy, or baseline urinary function. Suggested regimens for moderate hypofractionation include the 2 schedules used with the largest number of patients in randomized clinical trials: 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. Although moderately hypofractionated EBRT confers similar early cancer control and side effects as conventional fractionation, physicians should counsel patients about a small increased risk of short-term gastrointestinal toxicity and discuss how data are limited for oncologic outcomes beyond 5 years posttreatment.
Ultrahypofractionation (≥ 500 cGy) guidance varies by prostate cancer risk: For patients with low-risk disease who have opted for EBRT, it may be offered as an alternative to conventional fractionation; for those with intermediate-risk disease, it may be offered, but the expert panel strongly encourages treating these patients as part of a clinical trial or multi-institutional registry; for patients with high-risk disease, the panel does not suggest offering ultrahypofractionation outside of a trial or registry. Recommendations for ultrahypofractionation were graded by the panel as “conditional,” reflecting the limited base of current evidence on this approach. Suggested regimens for ultrahypofractionation include the 2 schedules used most commonly in published studies: 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. Consecutive daily treatments also should be avoided when using five fractions.
Recommendations also address the technical aspects of planning and delivering hypofractionated prostate radiation, including target and normal tissue volumes, dose constraints, margin definitions, and delivery techniques. The expert panel universally recommends the use of image-guided radiation therapy.
Benefits of Hypofractionation
“Men who opt to receive hypofractionated radiation therapy will be able to receive a shorter course of treatment, which is a welcomed benefit to many men. When clinicians can reduce overall treatment time while maintaining outcomes, it’s to our
Scott Morgan, MD, FRCPC
Daniel Barocas, MD
patients’ benefit, as they can spend less time away from family and less time traveling to and from treatment,” said Scott Morgan, MD, FRCPC, Assistant Professor of Radiation Oncology at the University of Ottawa and Co-Chair of the Guideline Panel.
“Image guidance and other advances in radiation therapy delivery have enabled radiation oncologists to treat prostate cancer with a therapeutic dose of radiation in a shorter treatment period than was previously possible,” said Daniel Barocas, MD, Associate Professor of Urology at Vanderbilt University Medical Center and guideline coauthor. “Results so far show comparable early cancer control to conventional fractionation while maintaining an acceptable side-effect profile. This has benefits to the patient in terms of reducing the treatment burden and cost and may increase the acceptability of external-beam radiation therapy.” ■
DISCLOSURE: For full disclosures of the authors, visit www.jco.ascopubs.org.
REFERENCES
1. Morgan SC, et al: Hypofractionated radiation therapy for localized prostate cancer: Executive Summary of an ASTRO, ASCO, and AUA evidence-based guideline. Pract Radiat Oncol 8:354-360, 2018.
2. Morgan SC, et al: J Clin Oncol. October 11, 2018 (early release online).
3. Morgan SC, et al: J Urol. October 9, 2018 (early release online).
4. Hamdy FC, et al: 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 375:1415-1424, 2016.
