Guideline supports shorter radiation therapy option in prostate cancer

The American Society for Radiation Oncology, ASCO and the American Urological Association have published a guideline supporting moderately hypofractionated external beam radiation therapy as an alternative to longer, conventional radiation courses for men with localized prostate cancer.

The motivation for the guideline — developed by a panel of clinicians and researchers — was twofold, according to co-author Howard Sandler, MD, MS, Ronald H. Bloom chair in cancer therapeutics and chair of the department of radiation oncology at Cedars-Sinai Medical Center,

“One, there is biological rationale to suspect that, for slow-growing tumors like prostate cancer, they might be safely and effectively treated with fewer radiation treatments,” he said. “Second, a number of important papers were published on the topic recently that rose the supporting data to a high enough level of evidence that we felt it was worth putting together a guideline document.”

The panel defined hypofractionation as 20 to 28 radiation treatments, as opposed to the standard 40 to 44 treatments. Ultrahypofractionated radiation therapy, which received a conditional recommendation from the task force, could bring the total down to as few as five treatments.

Eric M. Horwitz, MD, chair of the department of radiation oncology at Fox Chase Cancer Center, offered perspective on the more convenient approach to radiation therapy for these patients.

“The standard of care for generations has been 5 days a week for 2 months,” said Horwitz, who was not involved with the guideline development. “If there’s no other option, then men will do it. But if we can tell them they don’t have to come in here for 9 weeks, of course they’re going to say yes. Now we have the option to tell them that, yes, they can come in for a shorter period of time without losing anything in terms of safety and efficacy.”

Guideline overview

Moderate hypofractionation is defined as a fraction size of 240 cGy to 340 cGy, according to the authors. This approach may be offered as an alternative to standard fractionation — defined as 180 cGy to 200 cGy — for patients in any cancer risk group, anatomy or baseline urinary function category, and regardless of age or comorbidities.

“There was a particularly high level of evidence in favor of hypofractionation, with three strong and important randomized controlled trials,” Sandler said. “It can be used for men with low, intermediate and high-risk prostate cancer, as long as the lymph nodes aren’t being treated, and as long as there is active surveillance.”

More than 4,000 patients were involved in these trials, Sandler said.

The suggested schedules for moderate hypofractionation are 6,000 cGy administered in 20 fractions of 300 cGy over 4 weeks, or 7,000 cGy administered in 28 fractions of 250 cGy over 5.5 weeks.

A slight increase in short-term gastrointestinal toxicity may accompany moderately hypofractionated external beam radiation therapy, but that risk is minimal. Sandler said.

“We want to stress that the guideline process used for ASTRO, ASCO and AUA is very strict,” he said. “Studies were subject to very strict criteria.”

Fox Chase has been using hypofractionation for nearly 2 decades with few safety issues, according to Horwitz.

“We did the first trial for hypofractionation from 2002 through 2006,” he said. “We showed almost 20 years ago that this was a good way to treat men, and subsequent data have proven us out not only in terms of efficacy, but in how well the regimen is tolerated. The side-effect profile is basically the same as standard of care.”

Ultrahypofractionation — defined as 500 cGy or greater — may be offered to patients with low-risk disease, according to the guideline. If patients with intermediate- or high-risk disease are offered this approach, the authors of the guideline strongly recommend treatment in the context of a clinical trial or multiinstitutional registry.

“For ultrahypofractionation, the recommendations were based on a number of smaller studies, so the level of evidence is a bit weaker,” Sandler said. “We recommend this approach for low-risk patients, but there was less enthusiasm for intermediate- or high-risk patients.”

Sandler suggested that the primary motivation for patients choosing this regimen is convenience. “Although convenience is important, the guideline committee felt that we should be careful to make sure it is also safe and effective,” he said.

The authors suggest two schedules for ultrahypofractionation: 3,500 cGy in five fractions of 700 cGy, or 3,625 cGy in five fractions of 725 cGy. Patients should not receive 3,625 cGy in a fivefraction regimen outside of a trial or registry, according to the authors. When the five-fraction approach is used, patients should not receive consecutive daily treatments.

Other recommendations offer specifics about target and tissue volumes, dosing, margin definitions and methods for administering fractions. Imageguided radiation therapy is universally recommended.

Broader perspective

“As you know, this is a moving target,” Sandler said of hypofractionated external beam radiation therapy for prostate cancer. “Studies are ongoing right now, testing these schedules in various patient populations, including intermediate- and high-risk patients. The results of those studies were not available when we put this document together, but I suspect we will need to revise them at some point.”

Horwitz offered one more general caveat about hypofractionation.

“Men with big prostates who urinate a lot — and this has nothing to do with their cancer — are not good candidates for hypofractionation,” he said. “They are technically candidates, but this symptom of frequent urination will get worse with this process.”

The guidelines can be put into practice immediately, Sandler said.

“The pace of medical research is dynamic, and certainly subject to change,” Sandler said. “What we have offered is a good signpost along the road, based on the best information at this time. We expect that as the word spreads of hypofractionation, it will become more widely used.” — by Rob Volansky

For more information:

Eric M. Horwitz , MD, can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111; email: eric.horwitz@fccc.edu.

Howard Sandler, MD, MS, can be reached at Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048; email: howard.sandler@cshs.org.

Disclosures: Sandler reports stock and other ownership interests in Advanced Bioinformatics, consultant or advisory roles with Blue Earth Diagnostics, Dendreon, Ferring and Janssen, and a relationship with Caribou Publishing. Please see the guideline for all other authors’ relevant financial disclosures. Horwitz reports no relevant financial disclosures.