A shorter, more intense radiation therapy schedule conferred comparable DFS as a conventional schedule among men with low-risk prostate cancer, according to results of stratified, parallel-group study.
However, hypofractionated radiotherapy also increased risk for late grade 2 and 3 gastrointestinal and genitourinary adverse events.
“This study has public policy implications. Because the shorter regimen has advantages such as greater patient convenience and lower costs, it’s important to establish whether we can cure as many patients with the shorter regimen. Our study provides that information for the first time,” W. Robert Lee, MD, professor in the department of radiation oncology at Duke University School of Medicine, said in a press release. “These findings should help guide clinical decisions, and doctors should be comfortable recommending a shorter radiotherapy course as an alternative to the conventional schedule.”
Convention radiotherapy for localized prostate cancer includes 1.8 Gy to 2 Gy per treatment. That schedule requires administration 5 days per week for approximately 8 to 9 weeks, totaling 40 to 45 treatments and a dose range from 70 Gy to 81 Gy.
Lee and colleagues sought to evaluate whether hypofractionation — a higher dose given in fewer treatments — achieved comparable outcomes as conventional radiation.
The analysis included data from 1,092 men (median age, 67 years) with low-risk prostate cancer (clinical classification of T1b to T2c, Gleason score of 2-6 and PSA < 10).
Researchers randomly assigned the patients 1:1 to conventional (n=550) or hypofractionated (n=542) treatment regimen.
Those in the conventional group received 73.8 Gy in 41 fractions over 8.2 weeks, whereas those in the hypofractionated cohort received 70 Gy in 28 fractions over 5.6 weeks.
Median follow-up was 5.8 years. Researchers assessed patients every 3 months for the first 2 years, every 6 months the for the next 3 years and annually thereafter.
Researchers designed the trial to establish with 90% power that hypofractionated radiation results in a 5-year DFS that is not lower than that of conventional radiation by more than 7.65% (HR < 1.52).
The rate of 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the conventional arm and 86.3% (95% CI, 83.1 to 89) in the hypofractionated arm. The HR for DFS was 0.85 (95% CI, 0.64 to 1.14), which met the predefined noninferiority criterion.
Biochemical recurrence at 5 years occurred in 8.1% in the conventional arm and 6.3% in the hypofractionated arm. These data also demonstrated noninferiority of biochemical recurrence with hypofractionated vs. conventional radiation (HR = 0.77; 95% CI, 0.51-1.17; prespecified noninferiority criterion HR > 1.67 rejected).
A comparable proportion of patients in each arm achieved 5-year OS (93.2% vs. 92.5%; HR = 0.95; 95% CI, 0.64-1.41).
The incidence of early adverse events appeared comparable between the two arms.
However, patients who received the hypofractionated protocol were more likely to experience late GI (grade 2, RR = 1.59; 95% CI, 1.22-2.06; grade 3, RR = 1.55; 95% CI, 0.8-2.99) and genitourinary (grade 2, RR = 1.31; 95% CI, 1.07-1.61; grade 3, RR = 1.56; 95% CI, 0.76-3.18) toxicities.
The researchers acknowledged critics could argue that the prespecified noninferiority margin was wide, the dose in the conventional radiation arm was low and that some men with low-risk prostate cancer may not need any treatment.
Still, the results definitively show that the efficacy of 70 of Gy delivered in 28 fractions over 5.5 weeks is noninferior to 73.8 Gy delivered in 41 fractions over 8.25 weeks, despite an increase in adverse events, according to the researchers.
“These results are another example of NRG Oncology’s exemplary work in advancing the treatment of men with prostate cancer,” Walter J Curran Jr, MD, NRG Oncology Group chairperson, executive director of the Winship Cancer Institute of Emory University in Atlanta, and HemOnc Today Section Editor for Radiation Oncology, said in the press release. “This performance demonstrates the importance that the radiation oncology community places on learning whether a hypofractionated radiation schedule can both increase patient convenience and save health care resources.” – by Nick Andrews
Disclosure: Lee reports honoraria from Ferring and royalties or patents from UpToDate. Please see the study for a list of all other researchers’ relevant financial disclosures.