Among patients with 6 years’ follow-up, no differences were observed between ultra-hypofractionation and conventional fractionation in the rates of clinically relevant deterioration in overall urinary bother, overall bowel bother, overall sexual bother, or global health/QoL.
Ultra-hypofractionation was as well tolerated as conventional fractionation in patients with intermediate-to-high risk prostate cancer, according to a long-term, patient-reported quality of life (QoL) analysis from the phase 3 HYPO-RT-PC trial.1
“Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QoL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer,” the authors wrote.
The open-label, noninferiority, phase 3 HYPO-RT-PC trial was conducted at 12 sites in Sweden and Denmark, comprising 7 university hospitals and 5 country hospitals. The QoL assessment consisted of data from 1165 patients enrolled between July 1, 2005, and November 4, 2015.
To enroll on the trial, patients had to have histologically confirmed intermediate-to-high-risk prostate cancer. Specifically, patients had to have stage T1c–T3a disease, along with at least 1 of these risk factors: Gleason score ≥7, T3a disease, and/or a prostate-specific antigen level of 10 to 20 ng/mL with no detectable lymph node involvement or distant metastases. Other inclusion criteria were age ≤75 years and a WHO performance status of 0 to 2.
Patients were randomized in a 1:1 ratio to conventional fractionation (n = 582) or ultra-hypofractionation (n = 583). Conventional treatment consisted of 78.0 Gy in 39 fractions administered 5 days a week for 8 weeks. Ultra-hypofractionation consisted of 42.7 Gy in 7 fractions, administered 3 days per week for 2.5 weeks.
The study used 2 tools to assess QoL: the Prostate Cancer Symptom Scale (PCSS) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30). The study design stipulated that these assessments be made at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years.
For the QoL analysis, the median follow-up was 48 months and follow-up time for some patients extended up to 6 years. Specifically, 71% and 66% of the conventional fractionation and ultra-hypofractionation arms, respectively, completed questionnaires at 6 years.
Among patients receiving ultra-hypofractionation, the incidence rates of clinically relevant deteriorations at the end of radiotherapy was significantly higher for 7 out of 10 measured bowel symptoms or problems: stool frequency (P <.0001), rush to toilet (P = .0013), flatulence (P = .0013), bowel cramp (P <.0001), mucus (P = .0014), blood in stool (P <.0001), and limitation in daily activity (P = .0014).
At the end of radiotherapy, among 14 clinically relevant acute urinary symptoms or problems that were assessed, there was not a significant difference in incidence rates between the 2 treatment arms. There were also no reported differences in sexual functioning based on the radiotherapy methods used.
At subsequent follow-ups, no clinically relevant differences between the treatment arms were observed regarding bowel, urinary, or sexual functioning.
Among patients with 6 years’ follow-up, no differences were observed between the 2 radiotherapy arms in the rates of clinically relevant deterioration in overall urinary bother (P= .38), overall bowel bother (P = .33), overall sexual bother (P = .15), or global health/QoL (P= .41).
The previously reported primary outcomes from the HYPO-RT-PC trial showed ultra-hypofractionated radiotherapy is noninferior to conventionally fractionated radiotherapy in terms of failure-free survival.2 The estimated 5-year failure-free survival rate was 84% in both treatment arms (adjusted HR, 1.002; log-rank P = .99).
Safety data reported with the primary analysis showed that early side-effects presented more issues with ultra-hypofractionation; however, late toxicity was similar between the 2 radiotherapy arms, and, overall, ultra-hypofractionation was determined to have a noninferior toxicity profile.
1. Fransson P, Nilsson P, Gunnlaugsson A, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial [published online January 11, 2021]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30581-7
2. Widmark A, Gunnlaugsson A, Beckman L, et al. Ultrahypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet. 2019;394(10196):385-395. doi: 10.1016/S0140-6736(19)31131-6