Cancer patients require long-term management and ongoing care due to the chronic nature of their condition. Major cancer surgeries pose significant challenges, resulting in a decline in physiological and functional capacity. Traditionally, postoperative rehabilitation has been the most suitable intervention to improve functional recovery. Prehabilitation, which aims to enhance patients' functional capacity before surgery and to improve patients' ability to cope with physiological stress, is considered the best form of rehabilitation. Through multimodal strategies like exercise, nutrition and psychological support, prehabilitation can improve surgical outcomes for cancer patients. However, prehabilitation lacks objective assessment measures. Heart rate variability (HRV), a physiological parameter measuring variation in heartbeats, reflects autonomic nervous system activity and an increase in HRV is associated with fitness and recovery capacity in sports medicine. Psychological factors, nutritional status and physical exercise influence HRV. Hence, HRV could be used to objectively assess prehabilitation interventions. In addition, HRV is widely used in risk assessment in cardiology, and a reduction in HRV is recognized to be associated with complications and mortality. Despite its evident potential in risk assessment, HRV has never been utilized in preoperative assessments.
This is an international, multicenter, parallel-group, randomized study in chronic cancer patients undergoing surgery. Adult men and women patients who are eligible according to the inclusion/exclusion criteria will be randomized to study the effect of prehabilitation versus standard care on heart rate variability (HRV).
A total of 600 patients will be recruited by systematic screening of patients scheduled for elective surgical procedures. All patients undergoing major cancer surgery will be screened for eligibility and those who meet the inclusion/exclusion criteria will be approached for consent. Research personnel will use a web-based randomization system to assign patients (1:1 ratio) to either the prehabilitation or control arm. Study personnel will also collect data on recruitment rates, with reasons for non-enrollment.
Eligible patients will be randomly assigned to one of two treatments:
- Multimodal prehabilitation program for four weeks starting as soon as possible before surgery;
- Standard care.
The multimodal prehabilitation program will be individualized by carefully integrating and adapting various components to meet individual needs. The program will last four weeks (plus maintenance in case of delayed surgery), and will incorporate exercise training, nutritional therapy, and anxiety reduction techniques. After enrollment, patients will receive initial contact from trained personnel through telemedicine. To ensure personalized care, a comprehensive assessment will be conducted to identify specific physical, nutritional, or psychological challenges. Based on this assessment, a customized intervention plan will be prescribed to achieve tailored exercise training, optimized nutrition, and effective distress-coping strategies. Patients will be requested to download a dedicated smartphone application, which will comprehensively monitor and track their progress towards achieving their prehabilitation goals. After completing the four-week program, patients will continue a maintenance program until surgery.
The first HRV measurement will be performed for 5 minutes in an isolated room, after signing the written consent and before randomization, on the day of screening which occurs several weeks before surgery. The second HRV measurement will be performed the day before surgery. Both HRV time-domain measurements and HRV frequency-domain measurements will be evaluated.
