Hypofractionated Radiotherapy Not Noninferior to Standard Radiotherapy in Late Genitourinary and Gastrointestinal Toxicity in Prostate Cancer


Key Points

  • Hypofractionation was not noninferior to standard fractionation in late genitourinary or gastrointestinal toxicity in patients with prostate cancer in a Dutch phase III trial.
  • Efficacy outcomes have yet to be reported.

Hypofractionated radiotherapy was not noninferior to conventionally fractionated radiotherapy in late genitourinary and gastrointestinal toxicity in patients with prostate cancer in the Dutch phase III HYPRO trial. These findings were reported by Aluwini et al in The Lancet Oncology. An earlier report indicated a lack of noninferiority for acute genitourinary and gastrointestinal toxicity.

Study Details

In the trial, 820 patients aged 44 to 85 years from 7 centers in the Netherlands were randomized between March 2007 and December 2010 to receive hypofractionation (n = 410) or standard-fractionation radiotherapy (n = 410). Patients had stage T1b-T4, NX-0, MX-0 disease and a prostate-specific antigen level ≤ 60 ng/mL.

Hypofractionation consisted of 19 fractions of 3.4 Gy in 6.5 weeks (3 fractions per week), and standard fractionation consisted of 39 fractions of 2 Gy in 8 weeks (5 fractions per week). The primary endpoint was 5-year relapse-free survival.

Late Toxicity

The analysis of late toxicity included 395 evaluable patients in the hypofractionation group and 387 in the standard-fractionation group and. Median follow-up was 60 months.

At 3 years, grade ≥ 2 genitourinary toxicity had occurred in 41.3% (95% confidence interval [CI] = 36.6%–46.4%) of patients in the hypofractionation group vs 39.0% (95% CI = 34.2%–44.1%) in the standard-fractionation group (hazard ratio [HR] = 1.16, 90% CI = 0.98–1.38; noninferiority threshold = 1.11). Grade ≥ 2 gastrointestinal toxicity had occurred in 21.9% (95% CI = 18.1%–26.4%) vs 17.7% (95% CI = 14.1%–21.9%; HR = 1.19, 90% CI = 0.93–1.52; noninferiority threshold = 1.13). Grade ≥ 3 late genitourinary toxicity occurred in 19.0% vs 12.9% (P = .021), and grade ≥ 3 late gastrointestinal toxicity occurred in 3.3% vs 2.6% (P = .55).

The investigators concluded: “Our data could not confirm that hypofractionation was non-inferior for cumulative late genitourinary and gastrointestinal toxicity compared with standard fractionation. Before final conclusions can be made about the utility of hypofractionation, efficacy outcomes need to be reported.”

The study was funded by the Dutch Cancer Society.

Shafak Aluwini, MD, of Erasmus MC Cancer Institute, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.