Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs Conventional Radiotherapy

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.

Patient-Reported Functional Outcomes After Hypofractionated or Conventionally Fractionated Radiation for Prostate Cancer: A National Cohort Study in England

“…12 A recent trial comparing H-RT and C-RT in 962 low-risk prostate-cancer patients found no differences in patient-reported outcomes between 6 and 60 months after the start of treatment, expect for a statistically but not clinically significant decline in bowel function at 12 months only. 29 Three smaller RCTs utilising IMRT have also reported no significant differences in patientreported urinary, bowel, or sexual functioning measured using the EPIC-50 with short (3month) 30 and long-term follow-up (≤ 5 years). 31,32 The toxicity profiles will need to be reviewed in response to the introduction of other hypofractionation regimens.…”

Comparing bowel and urinary domains of patient‐reported quality of life at the end of and 3 months post radiotherapy between intensity‐modulated radiotherapy and proton beam therapy for clinically localized prostate cancer

“…There are various definitions of a clinically meaningful EPIC‐26 score change. In this study, we used the widely accepted definition of a clinical meaningful change as a score change >50% of the standard deviation of a baseline score 5‐7 . The minimally important differences (MID) can also be utilized as a threshold to define a clinically meaningful change.…”

“…In addition, for each RT modality, we assessed the statistical significance and clinical relevance of score changes at the end of RT and 3 months post‐RT. A clinically meaningful change at a specified point of time was defined as a score change that exceeds >50% of the standard deviation of a baseline score 5‐7 . The difference in the proportion of patients with clinically meaningful change between the two treatment modalities was also evaluated.…”

Moderately Hypofractionated Intensity Modulated Radiation Therapy with Simultaneous Integrated Boost for Prostate Cancer: Five-Year Toxicity Results from a Prospective Phase I/II Trial

“…These trials demonstrated equivalent BF, PCSM, overall survival (OS). [3][4][5][6][7][8][9][10][11][12][13] In 2018, this led to a joint ASTRO, ASCO, and AUA guideline recommending moderate hypofractionation be offered across low, intermediate, and high risk groups regardless of age, comorbidity, and urinary function. 14 Consensus opinion is that moderate hypofractionation has a similar risk of acute GU and late GU/GI toxicity compared to conventional EBRT with higher rates of acute GI toxicity.…”