HRQOL in Prostate Cancer Patients Treated With Radiotherapy (PRORAD)

Health-Related Quality of Life in Prostate Cancer Patients Treated With Radiotherapy

The study primarily aims at evaluating health-related quality of life after radiotherapy for prostate cancer, using modern hypofractionated radiotherapy schedules. Study design is a prospective observational cohort study. All patients give written informed consent and fill out online validated questionnaires before, during, and after radiotherapy (yearly) up to 5 years post-treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: radiotherapy

Detailed Description

Rationale: Patient-Reported Outcomes (PROs), such as health-related quality of life (HRQL), have achieved an important role in the evaluation of benefits and harms after cancer treatment, including radiotherapy for prostate cancer (PCa). In the past year, clinical radiotherapy protocols at the Erasmus MC have been changed for external beam radiotherapy (EBRT) as well as for brachytherapy (BT). In order to evaluate the current, changed, clinical practice, we will conduct a prospective cohort study, with the main purpose to assess HRQL for the current treatment options at the Erasmus MC.

Objective: To establish HRQL (start treatment - 5 years after treatment) in a prospective cohort of ≈600 patients with localized PCa treated with radiotherapy within in the period ≈ 1/3/2019 - 1/12/2023.

Main objective: to establish changes in HRQL levels (with respect to baseline) up to 5 year post-treatment, within each radiotherapy modality for prostate cancer patients, i.e. EBRT 60 Gy in 20 fractions, EBRT 42.7 Gy in 7 fractions, CyberKnife (stereotactic EBRT) 38 Gy in 4 fractions, BT 27 Gy in 2 fractions, postoperative EBRT (PORT) 72 Gy in 36 fractions, EBRT for LN+: 70 Gy (prostate)/52 Gy (lymph nodes) in 28 fractions.

Study design: Prospective observational cohort study. Study population: Patients with prostate cancer T1c-T4 referred for radiotherapy at the Erasmus MC as a primary treatment with curative intent or as first line adjuvant treatment after a prostatectomy.

Intervention: All interventions are according to applicable standard clinical procedures & protocols for localized prostate cancer of the Radiotherapy department.

Main study parameters/endpoints: HRQL scores of the EPIC (urinary domain, bowel domain), and the IIEF-5 (sexual function) score.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no additional risks or benefits for patients that participate in the study. The additional burden is to fill out questionnaires at regular intervals.

Study patient recruitment period was from April 2019 to May 2025, enrolling about 695 eligible patients, mainly treated with UHF 7x6.1 Gy (n=240), MHF 20x3/3.1 Gy (n=210), PORT (n=85), and brachytherapy (n=65).

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Radiotherapy, Erasmus MC Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Clinically T1c-T4, N0 (or N+ in case of EBRT-LN+), M0 prostate cancer patients referred for radiotherapy to the Erasmus Medical Center.

Description

Inclusion Criteria:

• Clinically T1c-T4, N0 (or N+ in case of EBRT-LN+), M0 prostate cancer patient referred for radiotherapy.
• Willing and capable to fill out Dutch questionnaires on health-related items at a computer (online questionnaires).
• Signed written Informed Consent.

Exclusion Criteria:

• Previously radiation treatment in the pelvic region, for any reason.
• Diagnosed with other tumor in the past 12 months or known with tumor progression of another tumor.
• Postoperative radiotherapy with dose levels < 72 Gy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Applied radiotherapy protocol (subcohort) 1; 60 Gy in 20 fractions of 3 Gy external beam radiotherapy	Radiation: radiotherapy; Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)
Applied radiotherapy protocol (subcohort) 2; 42.7 Gy in 7 fractions of 6.1 Gy external beam radiotherapy	Radiation: radiotherapy; Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)
Applied radiotherapy protocol (subcohort) 3; 38 Gy in 4 fractions of 9 Gy stereotactic external beam radiotherapy	Radiation: radiotherapy; Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)
Applied radiotherapy protocol (subcohort) 4; 27 Gy in 2 fractions of 13.5 Gy brachytherapy	Radiation: radiotherapy; Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)
Applied radiotherapy protocol (subcohort) 5; 72 Gy in 36 fractions of 2 Gy postoperative external beam radiotherapy	Radiation: radiotherapy; Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)
Applied radiotherapy protocol (subcohort) 6; 70 Gy in 35 fractions of 2 Gy on prostate combined with 52 Gy in 28 fractions of 2 Gy on pelvic lymph node areas, external beam radiotherapy.	Radiation: radiotherapy; Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EPIC questionnaire score on urinary domain	Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain score: a 0 to 100 scale with higher scores representing better HRQOL.	Year 1 - Year 4
EPIC questionnaire score on bowel domain	Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain score: a 0 to 100 scale with higher scores representing better HRQOL.	Year 1 - Year 4
Sexual functioning score on IIEF-5 questionnaire	Sexual functioning score on International Index of Erectile Function (IIEF-5) questionnaire: 1 to 25 scale, higher scores imply better function	Year 1- Year 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute rectal bleeding, on symptom checklist (patient-reported)	Rectal bleeding is scored on a symptom checklist on a Likert scale (bother: none, little, quite, a lot) (patient-reported), higher score means worse symptoms. This symptom checklist was locally developed and used in previous trials.	During radiotherapy - 3 months after radiotherapy
Acute mucous discharge, on symptom checklist (patient-reported)	Mucous discharge is scored on a symptom checklist on a Likert scale (bother: none, little, quite, a lot) (patient-reported), higher score means worse symptoms. This symptom checklist was locally developed and used in previous trials.	During radiotherapy - 3 months after radiotherapy
Late moderate to severe urinary incontinence	Score of 'more than once a week or daily leaking of urine' on the Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain.	Year 1 - Year 4
Late moderate to severe urinary frequency during the night	Score of 'moderate/big problem for waking up to urinate' on the Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain.	Year 1 - Year 4
Late moderate to severe incontinence for stools	Score of 'more than once a week or daily uncontrolled leakage of stools/feces' on the Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain.	Year 1 - Year 4
Late frequent bowel movements	Score of 'more than five' daily bowel movements on the Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain.	Year 1 - Year 4
Late erectile dysfunction	Score of 'very low/low confidence to get and keep an erection' on the International Index of Erectile Function (IIEF-5) questionnaire.	Year 1- Year 4

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
General health score on EQ-5D-5L questionnaire	General health score on EuroQoL 5-dimensions, 5-levels (EQ-5D-5L) questionnaire: total score between -1 - +1,higher score indicates better quality of life.	Year 1- Year 4
Acute moderate to severe rectal discomfort	Score of 'quite/a lot' for the symptom 'pain with stools' and/or 'cramping urge',	During radiotherapy - 3 months after radiotherapy
Late watery bowel movements	Score of 'moderate/big problem for watery bowel movements' on the Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain.	Year 1 - Year 4
Late gastrointestinal pain	Score of 'moderate/big problem for abdominal/pelvic/rectal pain' on the Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain.	Year 1 - Year 4

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Dutch Cancer Society
• Investigators: Principal Investigator: Luca Incrocci, MD PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Wei JT, Dunn RL, Litwin MS, Sandler HM, Sanda MG. Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology. 2000 Dec 20;56(6):899-905. doi: 10.1016/s0090-4295(00)00858-x.
• Utomo E, Blok BF, Pastoor H, Bangma CH, Korfage IJ. The measurement properties of the five-item International Index of Erectile Function (IIEF-5): a Dutch validation study. Andrology. 2015 Nov;3(6):1154-9. doi: 10.1111/andr.12112. Epub 2015 Oct 9.

Helpful Links

• Protocol Registration Quality Control Review Criteria of ClinicalTrials.gov

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: prostate cancer; radiotherapy; health-related quality of life; hypofractionation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: MEC-2018-1711; project nr 14259 (HYPROSTAR) (Other Grant/Funding Number: Dutch Cancer Society (KWF))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Datasets used for publications (in the future) will be made available upon request. Requests for taking part in meta-analyses initiated by other research groups will be considered after publication of the main endpoints.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No