Hypofractionated Radiotherapy Not Inferior to Conventional Radiotherapy in Low-Risk Prostate Cancer
Hypofractionated radiotherapy was not inferior to conventional radiotherapy in terms of disease-free survival among men with low-risk prostate cancer, according to the results of the phase III NRG Oncology RTOG 0415 trial reported in the Journal of Clinical Oncology by Lee et al. However, it was associated with a greater risk for late gastrointestinal and genitourinary adverse events.
Study Details
In the trial, 1,092 patients were randomized between April 2006 and December 2009 to receive hypofractionated radiotherapy given as 70 Gy in 28 fractions over 5.6 weeks (n = 550) or conventional radiotherapy given as 73.8 Gy in 41 fractions over 8.2 weeks (n = 542). Patients had to have clinical T1b to T2c disease, a Gleason score of 2 to 6, a prostate-specific antigen (PSA) level < 10 ng/mL, and no nodal or distant metastatic disease. The trial was designed to establish with 90% power and an α of 0.05 that treatment with hypofractionated radiotherapy resulted in 5-year disease-free survival not worse than conventional radiotherapy by > 7.65% (hazard ratio [HR] = 1.52).
For the hypofractionated and conventional groups, median age was 67 years (37% and 40% ≥ 70 years), 79% in both were white and 18% and 17% were black, median PSA was 5.4 ng/mL (< 4 ng/mL in 20% in both), Gleason score was 5 or 6 in 100% and > 99%, T stage was T1 in 80% and 76%, and the radiotherapy modality was three-dimensional conformal radiotherapy in 20% and 21% and intensity-modulated radiotherapy in 80% and 79%.
Disease-Free Survival
Median follow-up was 5.8 years. Five-year disease-free survival was 86.3% (95% confidence interval [CI] = 83.1%–89.0%) in the hypofractionated radiotherapy group vs 85.3% (95% CI = 81.9%–88.1%) in the conventional radiotherapy group. The hazard ratio was 0.85 (95% CI = 0.64–1.14), with the predefined noninferiority hazard ratio threshold of 1.52 being met (P < .001). The cumulative incidence of biochemical recurrence at 5 years was 6.3% (95% CI = 4.5%–8.6%) vs 8.1% (95% CI = 5.9%–10.6%), with the hazard ratio of 0.77 meeting the prespecified noninferiority criterion of 1.67 (P < .001).
Estimated 5-year overall survival was 92.5% (95% CI = 89.9%–94.5%) vs 93.2% (95% CI = 90.7%–95.1%), with the hazard ratio of 0.95 meeting the prespecified criterion of 1.54 (P = .008). The most common causes of death were cardiovascular disease and second cancers.
Toxicity
No differences in early grade 2 (9.9% vs 9.7%) or 3 (0.6% vs 0.6%) gastrointestinal or grade 2 (23.7% vs 24.7%) or 3 (3.3% vs 2.4%) genitourinary toxicity were observed. Patients receiving hypofractionated radiotherapy were at an increased risk of late gastrointestinal toxicity (18.3% vs 11.4% grade 2, relative risk [RR] = 1.59, P = .005; 4.1% vs 2.4% grade 3, RR = 1.55, P = .19) and genitourinary toxicity (26.2% vs 20.5% grade 2, RR = 1.31, P = .009; 3.5% vs 2.1% grade 3, RR = 1.56, P = .22).
The investigators concluded: “In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late [gastrointestinal]/genitourinary adverse events was observed in patients treated with [hypofractionated] radiotherapy.”
The study was supported by grants from the National Cancer Institute.
W. Robert Lee, MD, MS, MEd, of Duke University Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
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