New Guidelines Highlight Hypofractionation for Prostate Cancer

Pam Harrison

October 16, 2018

Men with early prostate cancer who choose active therapy rather than active surveillance should unreservedly be offered hypofractionated external-beam radiotherapy (EBRT) for the treatment of localized disease and, more tentatively, ultrahypofractionated EBRT as an alternative to convention fractionation, according to new guidelines.

The guidelines were developed by an expert committee from the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Urological Association.

They were published online October 11 in the Journal of Clinical Oncology.

In the guideline, conventional fractionation is defined as EBRT with a fraction size of 180 to 200 cGy; moderate hypofractionation is defined as EBRT with a fraction size between 240 cGy and 340 cGy; and ltrahypofractionation is defined as EBRT with a fraction size of 500 cGy or more.

"Compared to conventional fractionation, moderate hypofractionation confers similar prostate-cancer-control outcomes, similar rates of late toxicity, and only a slight excess in acute gastrointestinal toxicity," the expert panel writes.

Moreover, moderate hypofractionation is more convenient for patients, allowing patients to receive large doses of radiation across fewer treatment sessions, and utilizes healthcare resources well.

Thus, the task force were in "strong agreement" that the use of moderate hypofractionated EBRT should be offered to all men who chose EBRT for the treatment of their prostate cancer.

This recommendation applies to all risk groups and is independent of age, the presence of comorbidities, anatomy, or baseline urinary function, the panel members note.

"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, co-chair of the guideline panel and chair and professor of radiation oncology at Cedars-Sinai Medical Center in Los Angeles, California.

"Significant advances in treatment planning and delivery have enabled oncologists to deliver more powerful, lifesaving doses of radiation in fewer visits and without compromising quality of life," he said in a statement.

Key Clinical Questions

Under lead author Scott Morgan, MD, assistant professor of radiation oncology, University of Ottawa, Canada, who is the other co-chair of the guideline panel, the group of experts address eight key clinical questions in the new guidelines.

The first is how moderately hypofractionated EBRT compares to conventionally fractionated EBRT with respect to prostate cancer control, toxicity, and quality of life.

Having reviewed the literature and found that moderate hypofractionated EBRT compares favorably with conventional fractionated EBRT, the panel recommends that men at all levels of risk for prostate cancer moderate hypofractionation EBRT to the prostate with or without radiation to the seminal vesicles.

For men with high-risk prostate cancer, moderate hypofractionation should also be offered, but not to the pelvic lymph nodes.

In addition, "men should be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with moderate hypofractionation," the panel members caution.

Panel members could not single out one optimal regimen, because most of the multiple fractionation schemes explored in clinical trials have not been compared head to head.

However, they suggest that radiation oncologists choose a regimen of 6000 cGy delivered in 20 fractions of 300 cGy or a regimen of 7000 cGy delivered in 28 fractions of 250 cGy each.

They also indicate that men with either low-risk or intermediate-risk prostate cancer may be offered ultrahypofractionation as an alternative to conventional fractionation, although they do not recommend hypofractionation for men with high-risk disease outside of a clinical trial or a multi-institutional registry.

When offered to men with low- and intermediate-risk disease, ultrahypofractionated EBRT should be delivered in doses of 3500 to 3625 cGy in five fractions of 700 to 725 cGy to the planning target volume, provided the prostate is less than 100 cm3 in size.

Panel members also point out that at least two dose-volume constraint points for the rectum and bladder be used whenever moderately hypofractionated or ultrahypofractionated EBRT is delivered — one at the high-dose range, and one in the mid-dose range.

On the other hand, "five-fraction prostate ultrahypofractionation using consecutive daily treatments is not suggested, due to potential increased risk of late urinary and rectal toxicity," the panel members caution.

They also note that, with either modality, normal tissue constraints that differ from those of a published reference study should not be used, owing to acute and late toxicity risks.

Nor should the use of target volume and associated margin definitions for hypofractionated EBRT deviate from those of a published reference study, especially when using ultrahypofractionated regimens.

"IGRT [image-guided radiation therapy] is universally recommended when delivering moderately or ultrahypofractionated EBRT," the guideline authors emphasize.

In contrast, nonmodulated three-dimensional conformal radiotherapy techniques should be avoided when delivering either moderately hypfractionated or ultrahypofractionated prostate EBRT.

"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," coauthor Daniel Barocas, MD, associate professor of urology, Vanderbilt University Medical Center, Nashville, Tennessee, reaffirms in a statement.

"Results so far show comparable early cancer control to convention fractionation while maintaining an acceptable side effect profile," he added.

"This has benefits to the patient in terms of reducing the treatment burden and cost, and may increase the acceptability of EBRT," Barocas concluded.

Dr Morgan has served as a consultant or as an advisory board member for Janssen, Mayer, and Astellas Pharma. Dr Barocas has received honoraria from AstraZeneca, Tolmar, and Janssen and has served as a consultant or on an advisory board for these companies.

J Clin Oncol. Published online October 11, 2018. Full text

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