Is hypofractionated whole pelvis radiotherapy (WPRT) as well tolerated as conventionally fractionated WPRT in prostate cancer patients? The HOPE trial

Abstract

Background Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT. Methods Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm. Discussion To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.

Elective nodal radiotherapy in prostate cancer

“…11 Lastly, the biological dose to the prostate used in POP-RT is sufficient to optimise local control. 11 Indeed, local control plays an important role in optimising progression-free survival and metastasis-free survival, 11,15 and is linked to the dose delivered to the prostate. 24,57 Both the RTOG 9413 and GETUG-01 trials had this issue; 4 taking into account current knowledge, the dose delivered in these two studies was too low to guarantee sufficient local control.…”

“…24,57 Both the RTOG 9413 and GETUG-01 trials had this issue; 4 taking into account current knowledge, the dose delivered in these two studies was too low to guarantee sufficient local control. Consequently, the rate of local relapse was substantial and led to a second wave of distant metastasis, 15 which diluted the potential benefit of whole pelvis radiotherapy. 1,7,14 Results from Sandler and colleagues 8 confirmed that only when the primary tumour is controlled, whole pelvis radiotherapy might affect the outcome.…”

“…62,63 Although still in early development, hypofractionated and ultra-hypofractionated whole pelvis radiotherapy is currently widely investigated. 6,15,29,30 Despite short followup, preliminary results suggest that these approaches are safe 29,30 without affecting quality of life. 6 None of the randomised trials considered locoregional salvage treatment for isolated pelvic lymph node recurrence in patients receiving prostate-only radiotherapy, which is the most dominant site of recurrence.…”

“…9 An exploratory post-hoc analysis of the Medical Research Council PR07 trial 13 confirmed that there was no benefit of whole pelvis radiotherapy. Reasons for this finding might not necessarily be due to the absence of a benefit, but might be the result of incorrect patient selection (in patients with low risk and positive pelvic nodes the benefit of whole pelvis radiotherapy is often absent), [4][5][6]8,9,11,[14][15][16] inadequate treatment volume definition (not all pelvic nodal regions at risk were considered and consequently not irradiated), 2,4,5,7,[9][10][11]14,15,17,18 inappropriate technology used, 3,10,19 an insufficient dose, 4,[10][11][12]14,15,17,19,20 and inadequate use of concomitant and adjuvant androgen deprivation therapy. 9,11,17,20,21 In 2014, Dirix and colleagues 2 published a systematic review on this issue, analysing seven contemporary retrospective studies from 2006 to 2011 on elective pelvic radiotherapy.…”

Dosimetric Comparison of Ultra-Hypofractionated and Conventionally Fractionated Radiation Therapy Boosts for Patients with High-Risk Prostate Cancer

“…Improvement of a PCa cure is related to oncological, psychological, and economic issues [ 4 , 5 , 6 ]. Different fractionation schemes for radiation therapy were explored [ 7 , 8 , 9 , 10 ]. Clinical data for low- and intermediate-risk PCa show that treatment outcomes (i.e., genitourinary and gastrointestinal toxicities, biochemical relapse free survival (BRFS), overall survival (OS), and metastases-free survival (MFS)) after ultra-hypofractionated radiation therapy (UF-RT) are similar to conventional-fractionated radiation therapy (CF-RT) [ 11 ].…”