Data reinforce isodose MHFRT as standard of care radiotherapy regimen

Both isodose and dose-escalated moderately hypofractionated radiotherapy (MHFRT) showed comparable efficacy to conventionally-fractionated radiotherapy (CFRT) in patients with prostate cancer, though dose-escalated MHFRT was associated with greater odds of bowel toxicity, according to data from a recent meta-analysis published in Lancet Oncology.¹

The study assessed outcomes from 7 phase 3 trials.

With isodose MHFRT, there was no added risk of urinary or bowel toxicity compared with CFRT.

“We believe these data strongly support that isodose MHFRT should become the preferred standard of care MHFRT regimen for prostate cancer,” said co-lead author Amar U. Kishan, MD, executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA, in a news release on the findings.² “More broadly, there appears to be little reason to consider conventional radiotherapy over MHFRT for the types of patients enrolled in these trials given these results.”

In total, the study assessed outcomes from 7 phase 3 trials that compared MHFRT with CFRT. Of these, 3 studies compared isodose MHFRT with CFRT (n = 3454; median follow-up, 5.4 years) and 4 studies compared dose-escalated MHFRT with CFRT (n = 2426; median follow-up, 7.1 years).

In the studies comparing isodose MHFRT with CFRT, progression-free survival (PFS) was not statistically significant different between the 2 cohorts (HR, 0·92; 95% CI, 0·81–1·05; P = .21). Specifically, the estimated 5-year PFS was 77.0% (95% CI, 74.9%-77.0%) with MHFRT vs 75.6% (95% CI, 73.5%-75.6%) with CFRT.

The authors added, “There were also no significant differences in overall survival (HR, 0.83; 95% CI, 0.68–1.01; P = .06) or in progression-free survival detected after stratification by NCCN risk classification.”

Regarding safety, isodose MHFRT was not associated with an increased odds of 5-year late grade 2 or higher physician-scored genitourinary toxicity (OR, 1.16; 95% CI, 0.86–1.57; P = .32) nor late grade 3 or higher physician-scored genitourinary toxicity (OR, 1·15; 95% CI, 0.89–1.49; P = .27) compared with CFRT. Similarly, isodose MHFRT was not associated with an increased odds of late grade 2 or higher physician-scored gastrointestinal toxicity (OR, 1.30; 95% CI, 0.59–2.87; P = .51) or late grade 3 or higher gastrointestinal toxicity (OR, 0.89; 95% CI, 0.43–1.87; P = .76).

Additionally, patients in the isodose MHFRT arm did not experience an increased risk of 2x the minimally important clinical difference (MCID) in patient-reported urinary (OR, 1.03; 95% CI, 0.51–2.09; P = .93) or bowel (OR, 0.76; 95% CI, 0.40–1.43; P = .39) quality of life decrement compared with CFRT.

In the studies comparing dose-escalated MHFRT and CFRT, there was not statistically significant difference in PFS between the 2 arms, with an estimated 5-year PFS of 82.7% (95% CI, 80.5-84.9%) in the MHFRT arm vs 82.7% (95% CI, 80.5-84.9%) in the CFRT arm (HR, 0.94; 95% CI, 0.82–1.09; P = .43). The authors also noted no difference in overall survival nor PFS by National Comprehensive Cancer Center risk group.

Regarding safety, dose-escalated MHFRT was not associated with an increased odds of late grade 2 or higher physician-scored genitourinary toxicity (OR, 1.20; 95% CI, 0.95–1.51; P = .13), but was linked to a higher risk for grade 3 or higher genitourinary toxicity (OR, 1.53; 95% CI, 1.07–2.20; P = .021). Patients who received dose-escalated MHFRT also had an increased risk of late grade 2 or higher gastrointestinal toxicity (OR, 1.48; 95% CI, 1.14–1.92; P = .0035) and late grade 3 gastrointestinal toxicity (OR, 1.80; 95% CI, 1.08–3·00; P = .022).

Patients in the dose-escalated MHFRT also had significantly increased odds of experiencing a 2xMCID in bowel quality of life decrement vs patients who received CFRT (OR, 1.68; 95% CI, 1.07–2.61; P = .023). However, dose-escalated MHFRT was not associated with an increased odds of 2xMCID in urinary quality of life decrement (OR, 1.57; 95% CI, 0.87–2.85; P = .13).

“These findings reinforce isodose MHFRT as the standard of care, offering the same cancer control as conventional treatment but with fewer side effects than dose-escalated MHFRT,” said Kishan, who is also a researcher in the UCLA Health Jonsson Comprehensive Cancer Center. “Patients can safely opt for a shorter treatment schedule without compromising their outcomes, ensuring they receive effective care with fewer visits and minimal added risk. Less time in treatment can still mean the best possible results.”

REFERENCES

1. Kishan AU, Sun Y, Tree AC, et al. Hypofractionated radiotherapy for prostate cancer (HYDRA): an individual patient data meta-analysis of randomised trials in the MARCAP consortium. Lancet Oncol. 2025. doi: 10.1016/S1470-2045(25)00034-8

2. Study confirms safety and efficacy of higher-dose-per-day radiation for early-stage prostate cancer. News release. University of California, Los Angeles (UCLA), Health Sciences. March 18, 2025. Accessed March 20, 2025. https://www.newswise.com/articles/study-confirms-safety-and-efficacy-of-higher-dose-per-day-radiation-for-early-stage-prostate-cancer