GU Cancers Symposium 2012 - Hypofractionation for prostate cancer: Is less better? - Session Highlights

SAN FRANCISCO, CA, USA ( - Dr. W. Robert Lee expressed the potential advantages of a hypofractionation schedule (using fewer fractions with larger doses per fraction)

may result in an improved therapeutic fraction, while offering convenience and lower cost to the patient - and to the institution, improved resource utilization. This area of study is based on the fractionation sensitivity (alpha-beta ratio) of prostate cancer. In this presentation, Dr. Lee defined fractionation as: 1) conventional 1.8-2Gy; 2)moderate 2.4-4 Gy; and 3) extreme 6.5-10 Gy. Adding, “climb the pyramid to evidence-based medicine but recognized currently, there is no definitive radiation schedule for a curative treatment of prostate cancer.“ In the U.S., patients with prostate cancer receiving external beam radiation therapy typically are treated 5 days per week for 8 to 9 weeks. The typical dose per fraction is 1.8 to 2 Gy.

Dr. Lee reviewed results from three recent randomized trials of hypofractionation in prostate cancer. All three compared different fractionation schedules using contemporary methods and were designed with explicit alpha-beta ratio assumptions using some form of a superiority hypothesis. The Italian study was published recently and compared 80 Gy in 2 Gy fractions to 62 Gy in 3.1 Gy fractions. The other two studies were based in the U.S. (Fox Chase Cancer Center and M.D. Anderson). All three studies reported no consistent effect. In the Italian, study the hypofractionated arm reduced the risk of biochemical recurrence (with short follow-up). The U.S. studies found no difference between the arms (note: increased late genitourinary toxicity was detected in the Fox Chase study). In addition, the use of androgen suppression varies greatly from study to study.

Dr. Lee highlighted three newer inferiority studies currently underway. The Radiation Therapy Oncology Group (RTOG) study includes low-risk patients and has completed accrual. A Canadian study includes intermediate-risk patients and a study from by Metastasis Research Center will accrue more than 2,000 patients. All three of these studies are of noninferiority design with specific assumptions about alpha-beta.

In conclusion, Dr. Lee emphasizes there is a broad spectrum of hypofractionation. For consistency we should evaluate this treatment approach based on common definitions. To date, researchers have the largest experience with 2.4-4 Gy. While current randomized clinical trials of moderate hypofractionation have yielded inconsistent results, the newer larger studies are promising.

Overall, there is a very small experience with extreme hypofractionation. The studies on extreme hypo are non-randomized, small studies using 4 to 7 fractions of 6-10 Gy with less than 3 years follow-up. A trial from Sweden compares an extreme hypofractionation regimen to a conventionally fractionated regimen; however, until level 1 evidence becomes available, extreme schedules should be confined to the clinical research realm.

When asked about the hypofractionation spectrum, Dr. Lee responded that he is currently persuaded by the available data that 2.5-3 Gy is very safe. In a second question about the delivery device, he added, the biology underlying hypofractionation is fundamentally different than radiation therapy. It is possible to use various radiation machines to deliver hypofractionation.


Presented by W. Robert Lee, MD, MS, MEd1 at the 2012 Genitourinary Cancers Symposium - February 2 - 4, 2012 - San Francisco Marriott Marquis - San Francisco, California
1Duke University School of Medicine, Durham, NC

Reported for UroToday by Karen Roberts, Medical Writer



View Full 2012 GU Cancers Symposium Coverage