Geneva, Switzerland — Hypofractionated radiation therapy (HF) for intermediate- and high-risk prostate cancer results in similar late toxicity compared with standard fractionation (SF), according to new results from the Dutch Hypofractionation Trial (HYPRO).
"I think there is a role for hypofractionation in prostate cancer," Shafak Aluwini, MD, told Medscape Medical News, after presenting the findings here at the 2nd European Society for Radiotherapy & Oncology (ESTRO) Forum.
If both treatment approaches result in similar toxicity, "it's better to give the course in a shorter period because, especially for older people, this will improve their quality of life," said Dr. Aluwini, from Erasmus Medical Center in Rotterdam, the Netherlands.
It's too early yet for efficacy results from this study and another comparing HF vs SF in prostate cancer, and experts are urging patience until these results come in. At the same time, there is growing interest in HF as a way of reducing treatment costs while still delivering effective therapy.
HYPRO is a phase 3 trial conducted in 820 patients from 7 hospitals in the Netherlands. Patients were randomly assigned equally to SF (39 × 2 Gy fractions at 5 per week) or HF (19 × 3.4 Gy at 3 fractions per week).
All patients (mean age, 70.7 years) had high- or intermediate-risk prostate cancer without lymph node involvement, and more than two thirds used hormonal therapy.
The primary endpoints of the study were relapse-free survival (RFS) and overall toxicity scores, said Dr. Aluwini.
Although RFS has not yet been reported, at the meeting Dr. Aluwini reported that late gastrointestinal (GI) and genitourinary (GU) toxicities at a median follow-up of 43 months were available for 766 patients (378 in the SF group and 388 in the HF group).
Overall, late GI and GU toxicities did not significantly differ between the 2 groups, said Dr. Aluwini. "We can see that late toxicity can really be very late…even after more than 4 years," he noted.
For late GU toxicity, patients in the HF group had fewer grade 2 toxicities than those in the SF group (30% vs 34%) but had more grade 3 toxicities (15% vs 9%); however, this difference was not significant (P = .056). Grade 4 toxicities were seen in only 1% of patients in both groups.
Similarly, for late GI toxicity, patients in the HF group had more grade 2 toxicities than those in the SF group (19% vs 15%). Although the difference was not significant (P = .146), there was "a very low and equal" rate (2%) of grade 3 toxicities in both groups, and again, only 1% of grade 4 toxicities in both groups.
Multivariate analysis showed that acute toxicity was the most significant predictor for late toxicity. "This was highly significant," Dr. Aluwini said. "Patients presenting with acute toxicity had about 3 times the chance of getting late toxicity" (32% vs 12%; P = .000).
Age older than 70 years was also a significant predictor, with 50% of this age group showing late toxicity compared with 39% of younger patients (P = .002).
Finally, hormonal therapy was also predictive of late toxicity. Patients who were receiving HT were more likely to show late toxicity than those who were not receiving HT (47% vs 41%; P < .001).
"Fractionation dose does not significantly influence late toxicity, and the presence of acute toxicity and age were more important that dose of fractionation," Dr. Aluwini said, adding, "you also have this effect of age on toxicity with conventional fractionation."
He said the findings are important because the shortened schedule of hypofractionation may significantly improve quality of life: "We're looking at that now," he said.
New Findings Are Reassuring
Asked by Medscape Medical News to comment on the findings, session co-moderator Mary Gospodarowicz, MD, medical director of the Princess Margaret Cancer Centre at the University Health Network in Toronto, Ontario, Canada, said, "We're all a bit concerned about hypofractionation, and these studies are actually quite reassuring that the differences are small."
Regarding efficacy of the treatment, RFS results are not yet available. "We need at least 1 to 2 years more years to report results of the efficacy of the treatment," Dr. Aluwini told Medscape Medical News.
"There is increasing evidence that it could be advantageous. But the real proof will have to come with a good trial. The only 2 good trials are the CHHiP [Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer] trial and our trial. I think we have to wait 2 more years to get the real evidence from trials. At the moment we can say there are positive signals that hypofractionation could be helpful," he commented.
Efficacy results for the CHHiP trial have not yet been reported, but recently published safety data for the trial suggest that HF is associated with a rate and severity of adverse effects similar to those seen with SF (Lancet Oncol. 2012;13:43-54).
Principal investigator of the CHHiP trial, David Dearnaley, MD, professor of uro-oncology at the Institute of Cancer Research in Surrey, United Kingdom, said these new results from the HYDRO trial "are very reassuring" and complement the results from CHHiP. "We have 2 major challenges: firstly to find out whether these more intense but shorter courses of radiotherapy are as effective as the standard 7- to 8-week schedules, and secondly to continue to refine radiotherapy techniques to make treatment even safer," he told Medscape Medical News.
In addition, Dr. Dearnaley said intensity-modulated and image guidance techniques "show considerable promise and allow even more extreme hypofractionation using as few as 5 radiotherapy treatments."
"Efficacy is of course very important and we need patience to wait another 2-3 years before these results become available to decide whether shorter treatments should become the 'standard of care.' Well-constructed trials will give us the answers and these international efforts will be the foundation for guiding safe, effective and convenient radiotherapy treatments in the future which should use health resources efficiently."
In the United States, there is "growing interest in hypofractionated radiotherapy as a way to reduce the cost of prostate radiotherapy while still delivering effective treatment," added Sanjay Aneja, MD, and James Yu, MD, from the Department of Therapeutic Radiology at Yale University in New Haven, Connecticut, who recently published a review on this topic (Oncology (Williston Park). 2012;26:512-518).
"The HYPRO trial is a significant step in validating the safety of hypofractionated radiation compared to conventional fractionated treatment," they told Medscape Medical News. "However, until longer follow-up is reported, these alternative fractionation regimens should still be considered relatively experimental, particularly in comparison to standard fractionated intensity-modulated radiotherapy, which has a long and robust record of safety and effectiveness."
None of the speakers or interview subjects have disclosed any relevant financial relationships.
2nd European Society for Radiotherapy & Oncology (ESTRO) Forum. Abstract OC-0052. Presented April 20, 2013.
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Cite this: Hypofractionated Prostate Radiotherapy, Same Toxicity: Study - Medscape - Apr 23, 2013.