The breast cancer world is 10 years ahead of us [in prostate cancer] with adopting modest hypofractionation. For prostate cancer, however, the appropriate regimen remains to be defined.
—Daniel Hamstra, MD
Formal discussant of these trials Daniel Hamstra, MD, of Texas Center for Proton Therapy, Irving, offered his perspective. With increased doses of radiation using additional conventional fractions, tumor control is improved, but the risk of damage to normal tissue is increased. Hypofractionation is an approach that promises to “get off this sigmoidal curve,” he said.
“For the past 20 years, we have been increasing conventionally fractionated radiotherapy by using higher doses and more fractions and, at the same time, witnessing increased toxicity, predominately urinary toxicity, to the point where we could not go much further upping the dose,” Dr. Hamstra told the audience at the 2016 Genitourinary Cancers Symposium.
The rationale for conventional fractionation is that tumors are unaffected by fractionation, but by contrast, late effects seem to be influenced by fractionation. By giving multiple small fractions, there is an improvement in toxicities, he continued. It is possible that in prostate cancer, which may be sensitive to fractionation, these effects are reversed by giving a smaller number of fractions with higher doses (hypofractionation).
Both the NRG Oncology RTOG 0415 and CHHiP studies were noninferiority trials, and the curves for biochemical failure overlap. In both trials, bowel and bladder toxicity was similar with conventional vs hypofractionation therapy, with only a small increase in mild to moderate bowel toxicity.
At least four previous randomized trials postulated that hypofractionation would be superior to conventional fractionation, but this was not borne out in the previous studies. The current trials asked a question of noninferiority and were able to demonstrate that hypofractionation was noninferior to conventional fractionation in both trials.
“Hypofractionation is probably ready for prime time,” Dr. Hamstra stated, but will it be implemented in prostate cancer? “The breast cancer world is 10 years ahead of us [in prostate cancer] with adopting modest hypofractionation. For prostate cancer, however, the appropriate regimen remains to be defined. It will be intriguing to see if modest hypofractionation takes off, as described in RTOG 0415 and the UK CHHiP Trial, as there are a number of different hypofractionation regimens being tested, with some regimens bringing the fractions down to as low as 5 or 7,” he continued.
In summary, Dr. Hamstra called these “practice-changing” trials. “Hypofractionation is cost- and resource-effective treatment that is easier for the patient, and these trials with more than 4,000 patients demonstrate clearly that they are tested and safe,” he stated. ■
Disclosure: Dr. Hamstra’s financial disclosures are Varian Medical Systems, Myriad Genetics, Teva, and Novartis.
Separate phase III trials presented at the 2016 Genitourinary Cancers Symposium demonstrated that modest hypofractionated radiotherapy is noninferior to conventional radiotherapy for men with intermediate- and low-risk prostate cancer and should be considered a new standard of care.1,2 However, it...