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.

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.

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.

Patients are asked informed consent for data sharing with POLARIS consortium