Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs Conventional Radiotherapy: A Phase 3 Randomized Clinical Trial

Abstract

Importance: Hypofractionated radiotherapy (HRT) would be more convenient for men with low-risk prostate cancer and cost less than conventional radiotherapy (CRT) as long as HRT is noninferior to CRT in terms of survival and quality of life (QOL) is not found to be worse.

Objective: To assess differences in QOL between men with low-risk prostate cancer who are treated with HRT vs CRT.

Design, setting, and participants: In this phase 3 randomized clinical trial, men with low-risk prostate cancer were enrolled from sites within the National Cancer Institute's National Clinical Trials Network in the United States, Canada, and Switzerland.

Interventions: Random assignment to CRT (73.8 Gy in 41 fractions over 8.2 weeks) or to HRT (70 Gy in 28 fractions over 5.6 weeks).

Main outcomes and measures: Quality of life was assessed using the Expanded Prostate Index Composite questionnaire measuring bowel, urinary, sexual, and hormonal domains; the 25-item Hopkins Symptom Checklist measuring anxiety and depression; and the EuroQol-5 Dimension questionnaire measuring global QOL. All data were collected at baseline and 6, 12, 24, and 60 months. Change scores were compared between treatment arms using the Wilcoxon signed rank test. A significance level of .0125 to adjust for multiple comparisons was used for an overall 2-sided type 1 error of .05. Clinical significance was determined for the Expanded Prostate Index Composite change scores by an effect size of 0.5.

Results: Of 1092 patients analyzable for the primary end point, 962 (mean [SD] age, 66.6 [7.4] years) consented to the QOL component. No statistically significant differences with regard to baseline characteristics nor any of the QOL baseline domains were measured between arms. There were no differences in change score between arms with respect to any of the Expanded Prostate Index Composite questionnaire domain scores except at 12 months when the HRT arm had a larger decline than the CRT arm in the bowel domain (mean score, -7.5 vs -3.7, respectively; P<.001), but it did not reach clinical significance (effect size = 0.29). There were no differences between arms at any time point for the Hopkins Symptom Checklist nor EuroQol-5 Dimension questionnaire.

Conclusions and relevance: Treatment with HRT is noninferior to CRT in men with low-risk prostate cancer in terms of disease-free survival and, as shown in the present study, in prostate cancer-specific (eg, bowel, bladder, sexual) and general QOL, as well as in anxiety and depression. This study provides evidence to affirm that HRT is a practice standard for men with low-risk prostate cancer.

Trial registration: ClinicalTrials.gov identifier: NCT00331773.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Malone reports personal fees from Amgen, Sanofi, AstraZeneca, Bayer, Janssen, AbbVie, and TerSera. Dr Movsas reports grants from the National Cancer Institute, Varian, and Philips, as well as personal fees from ViewRay. Dr Nguyen reports personal fees from Ferring Pharmaceuticals, Nanobiotix, Janssen, Augmenix, Dendreon, Bayer, Astellas Pharma, GenomeDX, and Blue Earth Diagnostics, as well as grants from Janssen and Astellas Pharma. Dr Sandler reports personal fees from Ferring Pharmaceuticals, Blue Earth Diagnostics, Janssen, and Caribou Publishing, as well as grants from the American College of Radiology NRG Oncology. Dr Pugh reports personal fees from Millennium. No other disclosures are reported.

Figures

Figure.. CONSORT Flowchart

EPIC indicates the Expanded Prostate Cancer Index Composite questionnaire; EQ–5D, EuroQol–5 Dimension questionnaire; HSCL-25, Hopkins Symptom Checklist; QOL, quality of life; RT, radiotherapy.