HRQOL in Prostate Cancer Patients Treated With Radiotherapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Applied radiotherapy protocol (subcohort) 1<br>60 Gy in 20 fractions of 3 Gy external beam radiotherapy | Radiation: radiotherapy<br>* Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)<br>|
| Applied radiotherapy protocol (subcohort) 2<br>42.7 Gy in 7 fractions of 6.1 Gy external beam radiotherapy | Radiation: radiotherapy<br>* Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)<br>|
| Applied radiotherapy protocol (subcohort) 3<br>38 Gy in 4 fractions of 9 Gy stereotactic external beam radiotherapy | Radiation: radiotherapy<br>* Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)<br>|
| Applied radiotherapy protocol (subcohort) 4<br>27 Gy in 2 fractions of 13.5 Gy brachytherapy | Radiation: radiotherapy<br>* Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)<br>|
| Applied radiotherapy protocol (subcohort) 5<br>72 Gy in 36 fractions of 2 Gy postoperative external beam radiotherapy | Radiation: radiotherapy<br>* Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)<br>|
| Applied radiotherapy protocol (subcohort) 6<br>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<br>* Radiotherapy is delivered with linear accelerators or cyberknife (external beam radiotherapy), or local irradiation with high dose rate brachytherapy (brachytherapy)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, radiotherapy, hypofractionation, health-related quality of life