ASTRO 2016: Extremely Hypofractionated Radiation Therapy Shows Promising Toxicity Results for Intermediate-Risk Prostate Cancer
For men with intermediate-risk prostate cancer, side effects at 2 years following radiation therapy were comparable for extremely hypofractionated treatment, which was delivered in 7 fractions across 2.5 weeks, and conventional treatment of 39 fractions across 8 weeks, according to research presented at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA-5).
The HYPO-RT-PC trial, a randomized multi-institutional phase III trial in Scandinavia, was designed to assess outcomes from highly accelerated extreme hypofractionation, which is delivered in smaller number of high doses—seven fractions of 6.1 Gy each in this study.
“Randomized trials have confirmed the value of radiation dose escalation for prostate tumors, and the potential benefits of larger radiation doses in fewer fractions are expected to increase the therapeutic efficacy for men with prostate cancer,” said Anders Widmark, MD, Professor of Radiation Sciences at Umeå University in Umeå, Sweden, and lead author of the study. “Most of the existing data on hypofractionation, however, draws on cases of moderately accelerated radiation treatment of the prostate, in contrast to our study with more extreme hypofractionation. Our trial shows that patients experience similar side effects at 2 years with highly accelerated extreme hypofractionation.”
Trial Details
1,200 men with intermediate-risk prostate cancer were enrolled in the HYPO-RT-PC non-inferiority trial between 2005 and 2015. Eligible patients presented with tumor stages of T1c to T3a, prostate-specific androgen (PSA) levels of 20 or below, and one or two of three risk factors: stage T3a; a Gleason tumor score of 7 or higher; or a PSA level greater than 10.
Patients were randomized to one of two treatment arms. The conventional fractionation group received 78 Gy of image-guided radiotherapy to the prostate in 39 treatments of 2 Gy each over 8 weeks. The extreme hypofractionation group received 42.7 Gy in seven treatments of 6.1 Gy each over 2.5 weeks. Most patients (80%) received three-dimensional conformal radiotherapy (3DCRT), and the remaining patients received volumetric arc therapy (VMAT). Androgen-deprivation therapy was not allowed among study participants.
Primary outcomes included physician-reported side effects measured via a modified RTOG scale and patient-reported outcomes of urinary, bowel, and sexual function side effects measured with the Prostate Cancer Symptom Scale (PCSS) questionnaire. Side effects were measured prior to radiotherapy start (baseline); at the end of radiotherapy; and at 3, 6, 12, 18, and 24 months following completion of radiotherapy. Median follow-up time from randomization for the entire patient population was 4.2 years, and findings reflect the 866 patients who reached 2-year follow-up at the time of reporting in May 2016.
Findings
Men who received extremely hypofractionated RT in seven treatments experienced similar side effects 2 years following treatment as those who received conventional radiotherapy in 39 treatments. Rates of physician-reported grade 2+ toxicities at 2 years following treatment did not differ significantly between treatment arms. Urinary side effects were reported for 5.4% of extreme hypofractionation patients and 4.6% of conventional fractionation patients (P = .59). Bowel side effects were reported for 2.2% of extreme hypofractionation patients and 3.7% of conventional fractionation patients (P = .20). Impotence at 2 years posttreatment was reported in 34% of both groups, compared to 16% among all participants at baseline. Patient-reported outcomes at 2 years following treatment also did not differ significantly between treatment groups for overall bother from urinary (P = .17), bowel (P = .12), or sexual function (P = .71) symptoms.
Some modest but statistically significant differences emerged between the accelerated and conventional treatment arms in shorter-term bowel and urinary side effects. Acute urinary toxicity immediately following treatment was similar for both treatment groups (27.6% for extreme hypofractionation vs 22.8% for conventional fractionation, P = .11), although acute bowel toxicity at the end of radiotherapy was higher for the accelerated extreme hypofractionation treatment than for conventional fractionation (9.4% vs 5.3%; P = .023). Patient-reported bowel function at the end of radiotherapy was also significantly worse following extreme hypofractionation than following conventional fractionation for 7 of 10 symptoms assessed, although these differences dissipated at 3 and 6 months follow-up. At 1 year posttreatment, patient-reported urinary function was significantly worse among extreme hypofractionation patients for four of the 14 symptoms measured.
“The trial was designed to have equal late toxicity, so although there were some differences in shorter-term side effects, the results for long-term toxicity were precisely what we hoped to find,” said Dr. Widmark. “Our plan moving forward is to analyze primary endpoint data and present updated toxicity results approximately a year from now.”
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®.
