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].

— W. Robert Lee, MD, MS, Med

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In a phase III noninferiority trial (NRG Oncology RTOG 0415) reported in the Journal of Clinical Oncology, W. Robert Lee, MD, MS, Med, of Duke University Medical Center, and colleagues found that hypofractionated radiotherapy was not inferior to conventional radiotherapy in disease-free survival among men with low-risk prostate cancer.¹ Hypofractionated radiotherapy was, however, associated with a greater risk for mild late gastrointestinal and genitourinary adverse events.

Study Details

In the trial, 1,092 patients were randomly assigned 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, Gleason score of 2 to 6, 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 .05 that treatment with hypofractionated radiotherapy resulted in 5-year disease-free survival not worse than conventional radiotherapy by more than 7.65% (hazard ratio [HR] = 1.52).

For the hypofractionated and conventional radiotherapy 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 increased risk of mild to moderate 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].” ■

Disclosure: The study was supported by National Cancer Institute grants. For full disclosures of the study authors, visit jco.ascopubs.org.

Reference

1. Lee WR, Dignam JJ, Amin MB, et al: Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol 34:2325-2332, 2016.