Failure-Free Survival With Ultrahypofractionated vs Conventionally Fractionated Radiotherapy in Prostate Cancer
In the Scandinavian phase III HYPO-RT-PC trial reported in The Lancet, Widmark et al found that ultrahypofractionated radiotherapy was noninferior to conventionally fractionated radiotherapy in failure-free survival in patients with intermediate- to high- risk prostate cancer.
Study Details
In the open-label trial, 1,200 patients from 12 sites in Sweden and Denmark were randomly assigned between July 2005 and November 2015 to receive conventionally fractionated radiotherapy (n = 602) or ultrahypofractionated radiotherapy (n = 598). Of these, 1,180 (591 in the conventional-fractionation group and 589 in the ultrahypofractionation group) constituted the per-protocol population.
Most patents (89%) had intermediate-risk disease. Ultrahypofractionated radiotherapy consisted of 42.7 Gy in seven fractions 3 days per week for 2.5 weeks. Conventionally fractionated radiotherapy consisted of 78.0 Gy in 39 fractions 5 days per week for 8 weeks. No androgen-deprivation therapy was permitted.
The primary endpoint was time to biochemical or clinical failure in the per-protocol population. The prespecified noninferiority margin was 4% at 5 years, corresponding to a hazard ratio (HR) limit of 1.338.
Survival and Toxicity Outcomes
Median follow-up was 5.0 years. Estimated failure-free survival at 5 years was 84% in the ultrahypofractionated group vs 84% in the conventionally fractionated group (adjusted HR = 1.002, P = .99), establishing the noninferiority of ultrahypofractionation. Overall survival at 5 years was 94% vs 96% (HR = 1.11, 95% confidence interval = 0.73–1.69).
There was a borderline significant increased risk of acute Radiation Therapy Oncology Group grade ≥ 2 urinary toxicity in the ultrahypofractionated group at the end of radiotherapy (28% vs 23%, P = .057). No significant differences in grade ≥ 2 urinary or bowel late toxicity were observed between the two groups at any point after radiotherapy, apart from a higher rate of urinary toxicity in the ultrahypofractionated group at 1 year (6% vs 2%, P = .0037). At 5 years, there were no differences between groups in grade ≥ 2 urinary toxicity (5% vs 5%, P = 1.00) or bowel toxicity (1% vs 4%, P = .14).
The investigators concluded, “Ultrahypofractionated radiotherapy is noninferior to conventionally fractionated radiotherapy for intermediate- to high-risk prostate cancer regarding failure-free survival. Early side effects are more pronounced with ultrahypofractionation compared with conventional fractionation, whereas late toxicity is similar in both treatment groups. The results support the use of ultrahypofractionation for radiotherapy of prostate cancer.”
Anders Widmark, MD, of the Department of Radiation Sciences, Oncology, Umea University, Sweden, is the corresponding author for The Lancet article.
Disclosure: The study was funded by The Nordic Cancer Union, Swedish Cancer Society, and Swedish Research Council. For full disclosures of the study authors, visit thelancet.com.
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®.
