EffectiveNess of a multimodal preHAbilitation program in patieNts with bladder canCEr undergoing radical cystectomy: protocol of the ENHANCE multicentre randomised controlled trial

Abstract

IntroductionRadical cystectomy (RC) is the standard treatment for patients with non-metastatic muscle-invasive bladder cancer, as well as for patients with therapy refractory high-risk non-muscle invasive bladder cancer. However, 50–65% of patients undergoing RC experience perioperative complications. The risk, severity and impact of these complications is associated with a patient’s preoperative cardiorespiratory fitness, nutritional and smoking status and presence of anxiety and depression. There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the risk of complications and improve functional recovery after major cancer surgery. However, for bladder cancer the evidence is still limited. The aim of this study is to investigate the superiority of a multimodal prehabilitation programme versus standard-of-care in terms of reducing perioperative complications in patients with bladder cancer undergoing RC.Methods and analysisThis multicentre, open label, prospective, randomised controlled trial, will include 154 patients with bladder cancer undergoing RC. Patients are recruited from eight hospitals in The Netherlands and will be randomly (1:1) allocated to the intervention group receiving a structured multimodal prehabilitation programme of approximately 3–6 weeks, or to the control group receiving standard-of-care. The primary outcome is the proportion of patients who develop one or more grade ≥2 complications (according to the Clavien-Dindo classification) within 90 days of surgery. Secondary outcomes include cardiorespiratory fitness, length of hospital stay, health-related quality of life, tumour tissue biomarkers of hypoxia, immune cell infiltration and cost-effectiveness. Data collection will take place at baseline, before surgery and 4 and 12 weeks after surgery.Ethics and disseminationEthical approval for this study was granted by the Medical Ethics Committee NedMec (Amsterdam, The Netherlands) under reference number 22–595/NL78792.031.22. Results of the study will be published in international peer-reviewed journals.Trial registration numberNCT05480735.

How much does it cost to be fit for operation? The economics of prehabilitation

“…Moreover, digitalization would help lower the impact of staff and facility shortage. There are ongoing trials aiming to prove the clinical-as well as the cost-effectiveness of such programs [24][25][26][27]. Community based prehabilitation has also been proven to reduce postoperative complications [28], the cost-effectiveness of this type of programs is to be analysed in further studies.…”

Preoperative optimization of the radical cystectomy patient: Current state and future directions

“…62 The ENHANCE trial is presently investigating the effectiveness of MMP in patients undergoing RC measured by 90-day complications. 63 The study aims to accrue 154 patients and randomize them 1:1 to either multimodal prehabilitation or standard of care. The intervention arm will receive a physical therapist supervised exercise program with three training sessions per week, registered dietician guided nutritional support, psychologic counseling, and intensive smoking cessation counseling.…”

“…The ENHANCE trial is presently investigating the effectiveness of MMP in patients undergoing RC measured by 90‐day complications 63 . The study aims to accrue 154 patients and randomize them 1:1 to either multimodal prehabilitation or standard of care.…”

Nutritional Prehabilitation in Patients Undergoing Cystectomy: A Systematic Review

“…Multimodal prehabilitation programs, which include physical exercises and nutritional supplements, have demonstrated themselves to be feasible and effective, leading to positive improvements in patients’ physical fitness and functional status. While rapid recovery pathways have become a standard in many surgical settings to enhance postoperative recovery, the nutritional status, a predictor of postoperative morbidity and mortality in oncology patients, is often under-considered in urology [ 8 , 9 ]. Understanding the profile of patients before major surgery could facilitate and refine the surgical outcomes.…”