Comparison of hypofractionated high-dose intensity-modulated radiotherapy schedules for prostate cancer: Results from the phase III randomized CHHiP trial (CRUK/06/016).

Abstract

2 Background: We aimed to explore the dose response relationship for two 3 Gray (Gy) hypofractionated radiotherapy (hRT) schedules for localised prostate cancer (PCa). Methods: hRT schedules of 60Gy/20 fractions (f) and 57Gy/19f were compared with conventional RT (cRT) 74Gy/37f; iso-effective for alpha-beta ratios of 2.5Gy and 1.5Gy respectively. The trial was powered to demonstrate non-inferiority between each hRT schedule and cRT, with 3,213 patients (pt) needed to rule out 5% inferiority (80% power, 1-sided alpha 5%) assuming 70% event-free rate in cRT, corresponding to a critical hazard ratio (HR) of 1.21. The trial was not formally powered to directly compare the two hRT schedules. Pt with N0 T1b-T3a localised PCa were randomized (1:1:1 ratio). The primary endpoint was PCa progression (freedom from biochemical failure by Phoenix consensus guidelines or PCa recurrence). Acute toxicity was assessed up to 18 weeks post treatment and late side effects to 5 years (yr) by RTOG, LENT-SOM and patient reported outcomes (PROs). Results: 3,216 pts were randomized between 2002 and 2011; 1,065 (74Gy), 1,074 (60Gy), 1,077 (57Gy). Baseline characteristics were well balanced across groups: median age 69 yr; NCCN risk group 15% low, 73% intermediate, 12% high. With median follow up 5.2yr, 5yr progression-free rate (95% CI) was 74Gy: 88.3% (86.0%, 90.2%); 60Gy: 90.6% (88.5%, 92.3%), 57Gy: 85.9 (83.4, 88.0); HR60/74: 0.83, 90% CI (0.68, 1.03), HR57/74: 1.20, 90% CI (0.99, 1.45). Significantly more events were observed with 57Gy compared to 60Gy; HR57/60: 1.44, 90% CI (1.18, 1.75), log-rank p=0.003. No significant difference in acute RTOG bladder or bowel toxicity was observed between hRT schedules. Late toxicity profile was favorable; with grade 2+ RTOG bladder (60Gy: 16/960 (1.7%); 57Gy: 11/962 (1.1%), p=0.34) and bowel (60Gy: 28/960 (2.9%); 57Gy: 17/962 (1.8%), p=0.10) toxicity at 2yr. Analysis of LENT-SOM and PROs supported these results. Conclusions: With 5 yr follow-up treatment with a 3Gy schedule of 60Gy/20f shows improved treatment efficacy compared to 57Gy/19f and is non-inferior to 74Gy/37f with a similar low level of acute and late normal tissue damage. Clinical trial information: ISRCTN97182923.

Stereotactic body radiation therapy for low and intermediate risk prostate cancer—Results from a multi-institutional clinical trial

“…Radical prostatectomy (RP) series indicated five-year recurrencefree survival rates between 65 and 84% [23] for intermediate-risk PCa. Modestly hypofractionated regimens report FFBF rates of 82 and 90% in low and intermediate risk respectively [18,24]. The current study demonstrates improved results compared to previously published data, regardless of modality.…”

“…Though the current analysis still did not meet the stoppage rules, we recommend using doses less than 50 Gy. The patients with toxicity required significant surgical intervention as a result of treatment and the probability of toxicity is not warranted given the safety of modest hypofractionation with ADT or lower doses of SBRT [18]. The Phase I study was designed to assess late toxicity at 9 months after radiation therapy however 4 of 6 late GI toxicities occurred greater than 9 months after treatment.…”

Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know?

“…It is particularly useful for patients who benefit logistically from a shortened HF course like patients living at long distance from an RT centre or who have a poor support system [57, 58]. The results of three recently published phase III trials are summarised in Table 2 [59–61]. These trials revealed that HF is well tolerated, albeit with a slight increase in toxicity rates when compared to conventional schedules.…”

Early results of localised, high-risk prostate cancer treated by moderate hypo-fractionation (70 Gy at 2·5 Gy per fraction): 5-year experiences of a moderate hypo-fractionation regimen

“…[15][16][17] In addition, the recent phase III publications of this moderate hypo-fractionation regimen versus conventional fractionation showed non-inferiority in terms of biochemical control in a high-risk group. 18,19 In our institute, the schedule of 70 Gy at 2•5 Gy per fraction was adapted to treat localised prostate cancer at any level of risk in 2012. In this study we report the early results of moderate hypofractionation in 'high-risk' localised prostate cancer and evaluate the treatment results and toxicity of this regimen after implementation of this fractionation scheme for our population of patients.…”