EffectiveNess of a Multimodal preHAbilitation Program in patieNts With Bladder canCEr Undergoing Cystectomy

Study Overview
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Brief Summary
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Currently, the potential value of a multimodal prehabilitation program in bladder cancer has not been extensively studied. The investigators designed the ENHANCE study to assess the effect of a structured multimodal prehabilitation program in 154 patients with bladder cancer on the number (primary endpoint) and severity of complications within 90 days, length of hospital stay, readmissions, physical fitness, muscle strength, physical functioning, nutritional status, smoking behaviour, anxiety and depression, fatigue, quality of life, physical activity, tumor tissue characteristics, and healthcare costs.

Detailed Description
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The ENHANCE study is a multicenter, randomized controlled trial. The intervention group will participate in a prehabilitation program of 4-6 weeks before surgery, and additionally during neoadjuvant chemotherapy if applicable. The prehabilitation program consist of a tailored exercise program, nutritional support and if relevant smoking cessation and/or psychological counselling. The exercise program is under supervision of an oncology specialized physiotherapist and comprises aerobic-, resistance- and breathing- and relaxation exercises. Patients will be asked to be physically active for an additional 2 times a week for at least 30 minutes. A dietician will provide nutritional support and give dietary advice to increase protein intake to enhance the anabolic effect on muscle mass. Additionally, patients will receive a supplement containing 30 g of high quality whey-protein daily preferably before sleep and after the supervised training. Patients who score high on anxiety and depression will be offered a referral to a psychological support. Intensive counselling and nicotine replacement therapy will be offered to all patients who smoke. Patients in the intervention group will be asked to keep a diary to track unsupervised activity and to track intake of the protein supplementation. The physical activity level in both groups will be obtained via questionnaire.

Official Title
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EffectiveNess of a Multimodal preHAbilitation Program in patieNts With Bladder canCEr Undergoing Cystectomy. The ENHANCE Randomized Controlled Trial

Conditions
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Bladder Carcinoma

Intervention / Treatment
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* Behavioral: Prehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, primary, bladder cancer (cTa-4N0/N+M0), Planned to undergo radical cystectomy, Age ≥ 18 years. Exclusion Criteria: Subjects with severe cognitive or psychiatric disorders, Subjects who are operated within 3 weeks, Subjects with insufficient command of the Dutch language, which precludes them from following study instructions or completing study questionnaires, Subjects who have contraindications to safely perform exercise training or testing (i.e., CPET), Subject who are unable or unwilling to participate in the intervention.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prehabilitation group<br>The intervention group will participate in a prehabilitation program of approximately 4-6 weeks before surgery, and additionally during neoadjuvant chemotherapy if applicable. The program consist of a tailored exercise program, nutritional support and if relevant smoking cessation and/or psychological counselling. The exercise program is under supervision of an oncology specialized physiotherapist and comprises aerobic-, resistance- and breathing- and relaxation exercises. A dietician will provide nutritional support and give dietary advice to increase protein intake, including a supplement containing 30 g of whey-protein daily and after supervised training. Patients who score high on anxiety and depression will be offered a referral to a psychologist. Intensive counselling and nicotine replacement therapy will be offered to all patients who smoke. Patients will be asked to keep a diary to track unsupervised activity and to track intake of the protein supplementation. | Behavioral: Prehabilitation<br>* Multimodal prehabilitation program<br>|
| No Intervention: Control group<br>Patients randomized to the control group will receive care as usual according to local ERAS guideline implementation. In addition, they will receive a leaflet with the recent guidelines regarding physical activity, dietary advice, and smoking cessation. Their actual physical activity level will be obtained via questionnaire. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications | The proportion of patients having Clavien-Dindo grade 2 or higher perioperative complications; obtained from the medical records | 0-12 weeks post-surgery (measured 4 weeks and 12 weeks post-surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High grade complications | Clavien Dindo grade 3 or higher | 0-12 weeks post-surgery | 
| Duration of hospital stay | Time from admission until hospital discharge | 0-12 weeks post-surgery | 
| Readmissions | Hospital readmission as recorded in medical file | 0-12 weeks post-surgery | 
| Disease status | Progression/recurrence, any additional treatment as recorded in medical file | 0-12 weeks post-surgery | 
| Change in cardiorespiratory fitness | Assessed via cardiopulmonary exercise test (CPET) | T0a (baseline), T1 (within 1 week before surgery) | 
| Change in muscle strength | Grip strength | T0a (baseline), T1 (within 1 week before surgery), T3 (12 weeks post-surgery) | 
| Change in muscle strength | 30s chair stands | T0a (baseline), T1 (within 1 week before surgery), T3 (12 weeks post-surgery) | 
| Change in physical performance | Short Physical Performance Battery (SPPB) | T0a (baseline), T1 (within 1 week before surgery), T3 (12 weeks post-surgery) | 
| Change in nutritional status | Short Form- Patient Generated Subjective Global Assessment (SF-PGSA) | T0a (baseline), T1 (within 1 week before surgery), T3 (12 weeks post-surgery) | 
| Change in body composition | Fat free mass and fat mass assessed by Scale Bioelectrical Impedance Analysis (BIA) | T0a (baseline), T1 (within 1 week before surgery), T3 (12 weeks post-surgery) | 
| Nil per mouth consumption during hospitalization | The total days as recorded in medical file | 0-12 weeks post-surgery | 
| Change in weight | Measured in KG | T0a (baseline), T1 (within 1 week before surgery), T3 (12 weeks post-surgery) | 
| Height | Measured in cm | T0a (baseline) - T3 (12 weeks post-surgery) | 
| Change in smoking status | Self-developed questionnaire | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Sense of coherence (SOC) | 13-item SOC questionnaire | T0a (baseline) | 
| Change in fatigue | MFI questionnaire | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Change in HRQoL | EORTC QLQ-C30 | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Change in muscle invasive bladder cancer specific scores | EORTC QLQ-BLM30 | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Change in health status | EQ-5D-5L | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Change in physical activity | SQUASH questionnaire | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Change in anxiety and depression | HADS questionnaire | T0a (baseline), T0b (if applicable: after neoadjuvant chemotherapy), T1 (within 1 week before surgery), T2 (4 weeks post-surgery), T3 (12 weeks post-surgery) | 
| Intervention costs | Cost analysis | T0a (baseline) - T3 (12 weeks post-surgery) | 
| Healthcare resources consumption | Medical Consumption Questionnaire (iMCQ) | T0a (baseline) - T3 (12 weeks post-surgery) (measured within 1 week before surgery, 4 and 12 weeks post-surgery and if applicable : after neoadjuvant chemotherapy) | 
| Work status | Productivity Cost Questionnaire (iPCQ) | T0a (baseline) - T3 (12 weeks post-surgery) | 
| Satisfaction with prehabilitation in intervention group and evaluation in control group | Self-developed questionnaire | T3 (12 weeks post-surgery) | 
| Non participation analysis | Identify clinical and sociodemographic variables that are related to non-participation of patients in this trial via questionnaire | T0a (baseline) | 
| Hypoxia | To study the effectiveness of the prehabilitation program in terms of inducing favorable changes in tumor hypoxia markers | T3 (12 weeks post-surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prehabilitation, bladder cancer, exercise, smoking cessation, nutritional support, surgical complications, cystectomy