The CHHiP trial is a phase III non-inferiority study which accrued between October 2002 and June 2011 and randomized 3216 men across 71 centers in the United Kingdom to XRT in one of three dose schedules:
- 74 gy in 37 fractions
- 60 gy in 20 fractions
- 57 gy in 19 fractions
All patients received androgen deprivation therapy started at least 3 months prior to initiation of radiation therapy and stopped immediately after completion of radiation.
The primary outcome was biochemical recurrence-free survival, and a critical hazard ratio of 1.208 compared to the 74 gy regimen was chosen to declare either of the other two regimens non-inferior.
The original results of the CHHiP trial were published by Dr. Dearnaley et al in Lancet Oncology in 2016. These demonstrated non-inferiority of the 60 gy treatment regimen compared to the 74gy regimen in terms of 5 year biochemical recurrence-free survival (HR 0.84 [90% CI 0.68-1.03], p =0·0018). In fact, this HR numerically (and very nearly statistically significantly) favors superiority of the 67 gy regimen. The confidence interval for the HR of the 57 gy regimen included the critical value of 1.208, so non-inferiority could not be claimed (HR 1.20 [0.99-1.46], p=0.48).
These results, along with the PROFIT, RTOG 0415, and HYPRO trials form the backbone of the international consensus supporting the use of hypofractionation in prostate cancer, including in the more recent 2018 AUA/ASCO/ASTRO guidelines.
The results presented by Dr. Dearnaley showed these findings to be robust with 3 more years of follow up. With a median of 9.2 years of follow up, the 8 year biochemical recurrence-free survival for the 60 gy regimen was 83.7% vs 80.6% for 74gy and 78.5% for 57 gy. The hazard ratios for the 60 gy and 57 gy regimens were similarly essentially unchanged (HR 0.84 [90% CI 0.71, 0.99]; HR 1.17 (90% CI 1.00, 1.37) respectively).
Results for secondary endpoints were similar. 176 patients developed metastases over the course of the study, and metastasis-free survival was 95.6%, 95.3%, and 94.8% in the 74, 60, and 59 gy groups respectively. There were 567 overall deaths, which were driven overwhelmingly by non-prostate cancer mortality. Overall survival in the 3 groups was 85.9%, 88.6%, and 86.7% respectively.
Rates of toxicity were low. Clinician-assessed grade 3 or greater toxicity were 1.65, 2.0%, and 1.9% for bowel and 1.9%, 1.5%, and 1.9% for bladder. Patients reported “moderate” or “big” bother from bowel symptoms in 5.4%, 7.6%, and 5.3% of cases. Patients reported “moderate” or “big” bother from urinary symptoms in 6.7%, 9.3%, and 7.9% of cases. These patient-reported outcomes likely largely reflect bowel and bladder symptoms related to age rather than treatment effect, as the median age at enrollment was 69.
During the question-and-answer session, it was highlighted that CHHiP is one of only two trials to enroll high risk patients, a group that made up 19% of the study population. Dr. Dearnaley acknowledged that a subgroup analysis of only these high-risk patients has been much requested, but given that such a subgroup analysis was not a planned part of the study, he said that such data would likely never be presented. That said, he did express some openness to a general test of effect modification of fractionation schedule by risk category.
Presented by: David P. Dearnaley, MD The Royal Marsden National Health Service Foundation Trust
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA at the 2020 Genitourinary Cancers Symposium – February 13-16, San Francisco, CA @mcstroth at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
1. Dearnaley D, Syndikus I, Mossop H, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016;17(8):1047-1060.