High-Risk prostatE Cancer radiatiOn Versus surgERy

Study Overview
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Brief Summary
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Prospective cohort study comparing robot-assisted radical prostatectomy and external beam radiotherapy combined with androgen deprivation therapy for high-risk non-metastatic prostate cancer in terms of health-related quality of life, functional outcomes, cost-effectiveness, progression-free survival and distant metastasis-free survival.

Detailed Description
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Detailed description: Robot assisted radical prostatectomy (RARP) and external beam radiotherapy (EBRT) combined with Androgen Deprivation Therapy (ADT) are widely used treatment modalities for high-risk non-metastatic prostate cancer (HR-PCa). Both treatments are associated with adverse effects and can have a great impact on health-related quality of life (HRQoL). To date there is no consensus on which of both is the optimal treatment for men with HR-PCa, as it is unclear which treatment is superior in terms of HRQoL, cost-effectiveness, progression-free survival (PFS) and distant metastases-free survival (DMFS). This is reflected in substantial variation between individual hospitals in the utilization of both treatment options that is not explained by patient- and tumor characteristics or patient preferences. In the RECOVER study we aim to address this knowledge gap. The insights gained can be used to tailor recommendations in (national) guidelines and in shared decision-making tools. This allows healthcare professionals to better inform their patients and allows patients to make well-informed choices.

Official Title
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High-Risk prostatE Cancer radiatiOn Versus surgERy (RECOVER)

Conditions
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Prostate Cancer, Prostate Adenocarcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed de novo non-metastatic high-risk prostate cancer. cT3a-bN0M0, according to the 8th edition of the Tumour, Node, Metastasis (TNM) classification, with the exception that clinical T-stage will be based on digital rectal examination and magnetic resonance imaging (the highest stage will be used) and/or International Society of Urological Pathology (ISUP) grade ≥4 and/or Prostate-Specific Antigen (PSA) value at diagnosis greater than 20 ng/mL Fit for treatment with either RARP or EBRT and ADT (WHO performance status 0-1) Living in the Netherlands Able to read and understand the Dutch language Exclusion Criteria: Histological types other than adenocarcinoma Diagnosis and/or treatment in a hospital abroad Treatment with Androgen Receptor Targeted Agents (ARTA) as part of the initial treatment plan

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Robot assisted radical prostatectomy (RARP)<br>Robot-assisted radical prostatectomy, potentially as part of multimodality therapy with adjuvant radiotherapy or with (neo)adjuvant androgen deprivation therapy. Pelvic lymph node dissection (PLND) may be performed for staging purposes. The presence of positive lymph nodes (pN1) upon PLND is not a reason for exclusion and may be followed by adjuvant treatment such as lymph node irradiation. | |
| External beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT)<br>External beam radiotherapy (hypofractionated or conventionally fractionated) at a biologically effective dose converted to 2Gy fractions (α/β:1.5) of at least 76Gy. EBRT may be combined with a brachytherapy boost and PLND may be performed for staging purposes. The presence of positive lymph nodes (pN1) upon PLND is not a reason for exclusion and lymph node irradiation may be performed. Patients should receive ADT for at least 6 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional outcomes | Functional outcomes will be measured with the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). The EPIC-26 consists of 5 domains: urinary incontinence, urinary irritation, bowel function, sexual function and hormonal function. Domain scores range from 0-100 (the higher the score the better the function) and the minimally clinically important difference (MCID) per domain is 6-9, 5-7, 4-6, 10-12 and 4-6, respectively. | 3 years after treatment initiation | 
| Health-related quality of life (HRQoL) | HRQoL will be measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30). The questionnaire includes five functional domains (physical, role, cognitive, emotional and social), three symptom domains (fatigue, pain, nausea and vomiting) and a global health/quality of life scale. In addition, there are six separate items assessing dyspnea, insomnia, appetite loss, constipation, diarrhea, and perceived financial impact. For each domain and single item measure, a score from 0 to 100 can be calculated. For the functional domains and the global score, higher scores indicate a higher level of functioning/ better quality of life. In contrast, for the symptom domains and single item measures, a higher score represents a higher level of symptomatology. | 3 years after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-effectiveness | A cost-utility analysis (CUA) will be conducted from a societal and medical perspective. The societal perspective will specifically focus on the patients out of pocket costs. Utilities will be derived by means of a mapping algorithm for the EORTC QLQ-C30. The derived utility will be used to estimate a Quality adjusted life year (QALY) according to the trapezium rule. Incremental costs between EBRT combined with ADT and RARP will be related to incremental QALYs in a cost-utility ratio (ICUR). | 3 years after treatment initiation | 
| Progression-free survival |  | 5 years after diagnosis | 
| Distant metastases-free survival |  | 5 years after diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radical prostatectomy, Radiotherapy, Health-related quality of life, Functional outcomes, Progression-free survival, Distant metastases-free survival, Cost-effectiveness