A randomized phase III trial found that a hypofractionated radiotherapy (RT) regimen was not superior to, but generally equivalent to a conventional RT scheme in men with localized prostate cancer. The study joins a growing body of literature on hypofractionation in this malignancy, generally showing that the shorter courses are a reasonable option.
A low α-β ratio for prostate cancer has generated interest in hypofractionation, as it could increase the tumor dose without increasing toxicities. “Moreover, hypofractionated radiotherapy is delivered in fewer fractions, improving patients’ convenience, hospital logistics, and possibly reducing healthcare costs,” wrote study authors led by Luca Incrocci, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.
A study was presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago that found a hypofractionated regimen of 60 Gy in 20 fractions was noninferior to conventional RT. Another, presented this past January at the ASCO Genitourinary Cancers Symposium, again found a 60 Gy/20 fractions regimen was noninferior to conventional RT and to another hypofractionated regimen of 57 Gy/19 fractions.
The new HYPRO study, an open-label, randomized phase III trial, included 804 patients with intermediate- to high-risk localized prostate cancer treated at seven Dutch centers. A total of 407 patients received a hypofractionated RT course of 64.6 Gy in 19 fractions, and 397 received a conventional dose of 78 Gy in 39 fractions. The results were published online ahead of print in Lancet Oncology.
After a median follow-up period of 60 months, treatment failure occurred in 80 patients (20%) in the hypofractionation group and in 89 patients (22%) in the conventional RT group. The 5-year relapse-free survival rate was 80.5% in the hypofractionation group and 77.1% in the conventional group, for an adjusted hazard ratio (HR) of 0.86 (95% CI, 0.63–1.16; P = .36).
A post-hoc overall survival (OS) assessment was also similar between the groups. Hypofractionation patients had a 5-year OS rate of 86.2%, compared with 85.9% in the conventional RT group, for an HR of 1.02 (95% CI, 0.71–1.46; P = .92). Of 61 deaths among hypofractionation patients, 16 (26%) were related to prostate cancer; in the conventional patients, 15 of 59 deaths (25%) were related to the disease.
“The findings of our phase III trial provide no evidence for the postulated superiority of hypofractionated radiotherapy over conventional fractionation in terms of relapse-free survival in patients with intermediate-risk and high-risk localized prostate cancer,” the authors concluded.
In spite of the failure to show superiority, Incrocci’s center in the Netherlands will begin offering the shorter RT regimen to patients, though it will not become standard care. “The shorter therapy is as good as, but not better than the conventional therapy,” Incrocci said in a press release, adding that there were slightly more long-term side effects in the hypofractionation patients, which should be considered when deciding on an RT regimen. In particular, the incidence of grade 3 or worse nocturia was significantly higher with hypofractionation, which contributed to a significantly higher cumulative incidence of late genitourinary toxic effects (19% vs 13%; P = .021).
The HYPRO study will eventually be updated with 7-year results, which could shed more light on if and for whom a hypofractionated RT regimen is the best treatment option.