PROs Further Support Hypofractionated RT in Nonmetastatic Prostate Cancer

The use of moderately hypofractionated radiation therapy demonstrated no statistically significant differences in functional outcomes compared with conventionally fractionated radiation therapy, further cementing hypofractionated radiation therapy as a standard approach for patients with nonmetastatic prostate cancer.

Julie Nossiter, PhD

The use of moderately hypofractionated radiation therapy (H-RT) demonstrated no statistically significant differences in functional outcomes compared with conventionally fractionated radiation therapy (C-RT), further cementing H-RT as a standard approach for patients with nonmetastatic prostate cancer, according to patient-reported outcomes from a national cohort study.1

Findings showed that H-RT was associated with small increases in adjusted mean Expanded Prostate Cancer Index Composite short-form 26 sexual (3.3 points; 95% CI, 2.1-4.5; P <.001) and hormonal function scores (3.2 points; 95% CI, 1.8-4.6; P <.001), neither of which met established thresholds for a clinically meaningful change. Moreover, there were no statistically significant differences in urinary or bowel function, as well as quality of life (QoL), between the 2 approaches.

“To our knowledge, our study is the first national population-based prospective study to compare patient-reported outcomes and health-related quality of life in men undergoing C-RT or H-RT. Previous observational studies have demonstrated similar clinician-reported genitourinary/gastrointestinal toxicities in retrospective comparisons with C-RT,” first author Julie Nossiter, PhD, London School of Hygiene and Tropical Medicine, and coinvestigators wrote.

The trial evaluated all men diagnosed with prostate cancer from April 2014 to September 2016 in the English National Health Service who underwent a C-RT or H-RT; these patients, who were identified in the National Prostate Cancer Audit, were mailed a survey ≥18 months after their diagnosis.

The questionnaire included the Expanded Prostate Cancer Index Composite, which was meant to measure patient function and bother. Differences were estimated from patient surveys in the areas of urinary, bowel, sexual, and hormonal function and a health-related QoL scale in the areas of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression from a scale of 0 to 100 and 0 to 1.

Both rating systems used linear regression with adjustments for patient, tumor, and treatment-related factors in addition to gastrointestinal (GI) and (GU) baseline function, with higher scores representing better outcomes.

Of 17,058 participants, 77% (n = 13,131) responded to the survey. Of these, 64.2% had received C-RT and 35.8% received H-RT. In the H-RT group, 67.5% of patients were ≥70 years of age versus 60.9% in the C-RT arm. Fewer men had locally advanced disease in the H-RT group at 56.5% versus 71.3% in the C-RT group. Moreover, 79.5% versus 87.8% were less likely to receive androgen deprivation therapy in the H-RT and C-RT arms, respectively, and pretreatment GU procedures were conducted in 24.2% versus 21.2%, respectively.

Most men received radiation within 9 months of diagnosis (90.6%) and completed the survey ≥12 months after the start of radiation therapy (88.6%). Compared with C-RT, H-RT was associated with higher sexual function (95% CI, 2.1-4.5; P <.001) and hormonal function scores (95% CI, 1.8-4.6; P < .001). There were no significant differences in urinary incontinence, urinary obstruction, or bowel function and index scores, or in EuroQol EQ-5D-5L index scores, between both groups.

The frequency of men who indicated that their functioning was an issue at time of diagnosis was similar between both groups: 10.8% in the H-RT group versus 12.2% in the C-RT group for urinary function, 1.9% versus 2.3% for bowel function, and 19.5% versus 19.9% for sexual function, respectively.

“Results of this contemporary, large, national cohort study provide evidence that there are no clinically significant differences in functional outcomes and [health-related quality of life] between men receiving H-RT versus C-RT in real-world clinical practice,” Nossiter and coinvestigators wrote. “This supports recent guidelines that recommend H-RT with a moderately hypofractionated regimen as the standard of care for men with nonmetastatic [prostate cancer].”

Prior studies have compared the use of H-RT and C-RT in prostate cancer. The randomized, multicenter, phase III HYPRO trial found that at 3 months after radiotherapy, 22% in the C-RT group and 23% in the H-RT group reported grade ≥2 GU toxicity; the rate of grade ≥2 GI toxicity was similar between arms at 13%.2 One patient in each group experienced a grade 4 acute GU toxicity; 0% experienced grade 4 acute GI toxicities. Overall, results showed that H-RT was inferior to C-RT in terms of acute toxicity.

The multicenter, randomized CHHiP study collected results from patients with localized prostate cancer who underwent C-RT or hypofractionated high-dose intensity-modulated radiation. Approximately 153 men were randomized to receive conventional treatment at 74 Gy, 60 Gy, or 57 Gy—the latter of 2 were hypofractionated schedules. At 50.5 months of median follow-up, 4.3% in the 74 Gy group, 3.6% in the 60 Gy group, and 1.4% in the 57 Gy group experienced grade ≥2 bowel toxicity.3 A total 2.2%, 2.2%, and 0% had grade ≥2 bladder toxicity, respectively, as assessed by the Radiation Therapy Oncology Group scale. Investigators concluded that H-RT was equally well tolerated compared with C-RT at 2 years.


  1. Nossiter J, Sujenthiran A, Cowling TE, et al. Patient-reported functional outcomes after hypofractionated or conventionally fractionated radiation for prostate cancer: a national cohort study in England. J Clin Oncol. 2020;38(7):744-761. doi: 10.1200/JCO.19.01538
  2. Aluwini S, Pos F, Schimmel E, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): acute toxicity results from a randomised non-inferiority phase 3 trial. Lancet Oncol. 2015;16(3):274-283. doi: 10.1016/S1470-2045(14)70482-6
  3. Dearnaley D, Syndikus I, Sumo G, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHIP randomised controlled trial. Lancet Oncol. 2012;13(1):43-54. doi: 10.1016/S1470-2045(11)70293-5