Side effects experienced with extremely hypofractionated treatment for intermediate-risk prostate cancer were comparable to those of conventional radiation therapy at 2 years after treatment, according to research presented at the 2016 annual meeting of the American Society for Radiation Oncology.1
The HYPO-RT-PC trial (Phase III study of HYPOfractionated RadioTherapy of intermediate risk localised prostate cancer; ISRCTN registry identifier ISRCTN45905321) assessed outcomes from highly accelerated extreme hypofractionation, delivered in 7 fractions across 2.5 weeks vs conventional treatment delivered in 39 fractions across 8 weeks. The HYPO-RT-PC trial is a randomized multi-institutional phase III trial from Scandinavian cancer centers.
The benefits of radiation dose escalation and larger radiation doses in fewer fractions are proven to improve the therapeutic efficacy of radiation therapy for prostate cancer. However, most data on hypofractionation for prostate cancer were drawn from cases in which radiation treatment was moderately accelerated, whereas this study assessed more extreme hypofractionation. “Our trial shows that patients experience similar side effects at 2 years with highly accelerated extreme hypofractionation,” explained Anders Widmark, MD, a professor of radiation sciences at Umeå University in Umeå, Sweden, and lead author of the study.
For this study, the researchers enrolled 1200 men with prostate cancer tumor stages T1c to T3a, prostate-specific androgen (PSA) levels of 20.0 ng/mL or less, and 1 or 2 of the following risk factors: stage T3a, Gleason tumor score 7 or higher, or PSA level greater than 10.0 ng/mL. Participants were randomized to receive conventional fractionation (CF group) or extreme hypofractionation (E-HF group).
Conventional fractionation was 78 Gy of image-guided radiation therapy to the prostate delivered in 39 fractions of 2 Gy each over 8 weeks. Extreme hypofractionation was 42.7 Gy delivered in 7 fractions of 6.1 Gy each over 2.5 weeks. Most patients (80%) received 3-dimensional conformal RT (3DCRT), and the remaining patients received volumetric arc therapy (VMAT). Study participants were not allowed to receive androgen deprivation therapy.
Outcomes measured included physician-reported side effects via a modified RTOG scale and patient-reported urinary, bowel, and sexual function side effects via the Prostate Cancer Symptom Scale (PCSS) questionnaire. Measurements were obtained at baseline, at the end of radiation therapy, and at 3, 6, 12, 18, and 24 months after completion of radiation therapy. Median follow-up from randomization was 4.2 years, with 866 participants reaching 2-year follow-up by May 2016.
At 2 years after treatment, side effects experienced by men in the E-HF group were similar to those experienced by the men in the CF group. Rates of physician-reported grade 2 or higher toxicities were not significantly different between the 2 groups. Side effects reported for the E-HF group vs the CF group, respectively, were urinary, 5.4% vs 4.6% (P =.59) and bowel, 2.2% vs 3.7% (P =.20).
Impotence rates were 16% among all participants at baseline; however, at 2 years posttreatment, it was reported in 34% of both groups. Patient-reported overall bother from urinary (P =.17), bowel (P =.12) or sexual function (P =.71) symptoms at 2 years following treatment also did not differ significantly between groups.
Some modest but statistically significant differences were seen between the accelerated and conventional treatment arms for shorter-term bowel and urinary side effects. Acute urinary toxicity immediately after treatment was similar for both groups (27.6% for E-HF vs 22.8% for CF, P =.11), although acute bowel toxicity at the end of radiation therapy was higher in the E-HF group than in the CF group (9.4% vs 5.3%, respectively; P =.023). Patient-reported bowel function after completing radiation therapy was also significantly worse after E-HF than after CF for 7 of 10 symptoms assessed; however, these differences disappeared at 3 and 6 months follow-up. At one year posttreatment, patient-reported urinary function was significantly worse among patients in the E-HF group for 4 of the 14 symptoms measured.
1. Extremely hypofractionated radiation therapy shows promising toxicity results for intermediate risk prostate cancer patients. Boston, MA; September 26, 2016. https://mail.google.com/mail/b/475/u/0/#label/News%2FWEBEX/157666a586ea8909. Accessed October 3, 2016.