This protocol describes a translational, implementation study that will investigate a multimodal prehabilitation intervention, in a nonblinded, nonrandomized, single-group, pre-post design, in patients with colorectal cancer and upper gastrointestinal cancer undergoing potentially curative intent surgery at Concord Repatriation General Hospital, a tertiary teaching hospital in Sydney, Australia. The study will be evaluated using the RE-AIM Evaluation framework [22,23] (Table 1). Exploratory comparisons of some secondary end points will be made with historical colorectal cancer and upper gastrointestinal patient data obtained from the hospital’s surgical database. The minimum recruitment period will be 12 months. Recruitment commenced in January 2020.

Ethics approval was granted by Concord Repatriation General Hospital Human Research Ethics Committee under reference number 2019/PID13679, and the study was registered on the Australian and New Zealand Clinical Trials Registry (ACTR 12620000409976). The study will be performed in accordance with the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (Commonwealth of Australia, 2007 and updates) and the World Medical Assembly (Helsinki 2017 and updates).

Patients will be considered eligible if they are 18 years or older, undergoing elective colorectal cancer or upper gastrointestinal cancer resection with curative intent at the Concord Repatriation General Hospital with a minimum of 14 days prior to surgery for the intervention. All participants must be medically fit to exercise as determined by their treating physician, willing to attend supervised exercise sessions at the Sydney Cancer Survivorship Gym Concord Repatriation General Hospital 1-2 times per week, take prescribed high protein oral nutritional supplements, and have Eastern Co-operative Oncology Group performance status of 0-2 [24]. Patients treated with neoadjuvant chemotherapy or radiotherapy are eligible to participate after completion of neoadjuvant chemotherapy or radiotherapy provided there is a 14-day intervention time available before surgery. Patients who do not speak English are eligible and will be provided with a professional health interpreter. Inclusion and exclusion criteria are further outlined in Textbox 1.

Patients will be referred directly by their surgeon or oncologist or screened in a preadmission clinic for eligibility. Patient flow throughout the study is presented in Figure 1. The study coordinator or cancer nurse specialist will screen and contact eligible patients to explain the study. After consent, a baseline assessment will be conducted in eligible participants within 1-2 days of referral from the surgeon or preadmission clinic visit. Day 1 of the intervention period will be the day of the baseline assessment.

The duration of the intervention will vary depending on the scheduled surgery date but will run over 2-4 weeks (minimum of 14 days). The intervention is outlined in Figure 2.

An accredited exercise physiologist will assess the participant’s mobility and exercise capacity during the baseline assessment. Participants must commit to a minimum of one 60-minute weekly supervised session but will be encouraged to attend two 60-minute supervised exercise sessions per week.

Exercise sessions will include both aerobic and resistance exercise training. These sessions will be individually prescribed, facilitated, and monitored by an accredited exercise physiologist at the Sydney Cancer Survivorship Gym, Concord Cancer Centre. Exercise sessions will be delivered either individually or in a small group-based format with other cancer survivors. All participants will complete a warm-up routine consisting of dynamic stretching and a range of motion exercises. Participants will complete 20 minutes of aerobic exercise per 60-minute session with a target intensity of 60%-75% of heart rate reserve. Aerobic exercise may include the use of a cycle ergometer, treadmill, rowing ergometer, elliptical trainer, boxing due to equipment availability, and will be selected depending on participants’ preference and capability. The remainder of each session will focus on resistance exercises targeting large muscle groups through multijoint movements and use body weight, hand weights, resistance bands, or cable machine exercises. Participants are assisted in completing 2 sets of 8-12 repetitions for each movement with a target rating of perceived exertion of 13-15, measured using Borg’s Rating of Perceived Exertion 6-20 scale [26]. Heart rate and rating of perceived exertion will be recorded throughout each session for safety monitoring and exercise prescription purposes. The exercise volume and intensity will be adjusted by the exercise physiologist in a stepwise fashion.

Participants will be advised to participate in a nonhospital–based aerobic exercise (eg, walk, jog, cycle, swim, and step) program tailored to their baseline ability on at least 5 days per 7-day period. The target duration is a minimum of 30 minutes (continuous or broken into shorter bouts) per day at a self-rated perceived exertion of moderate intensity (13-15). An exercise diary and instructions will be provided to capture the frequency, intensity, time, and type of exercise. During the supervised exercise sessions, the exercise physiologist will provide support to promote program compliance, progression, and adherence.

Nutritional assessments will be completed by an Accredited Dietitian at baseline, before surgery, and 30 days after surgery, using The Patient-Generated Subjective Global Assessment [27]. Other assessments include body composition measured using bioelectrical impedance analysis (The Seca mBCA 515 Analyser) and a diet assessment (calories and protein) using a 24-hour diet recall.

Participants will receive a 200 mL bottle high protein oral nutritional supplement (Fresubin Protein Energy Drink, Fresenius Kabi) containing 20 g protein and 300 kcal per 200-mL bottle to be consumed daily within 60 minutes after exercise to support muscle synthesis [28-30]. Fresubin Protein Energy Drink is taken in addition to normal food and protein intake. Oral nutritional supplement tolerance will be assessed and recorded by the study dietitian. Dietary advice and written material will be provided with the aim of assisting the participant to achieve a protein intake (spread across meals) of 1.2-1.5 g per kg per body weight (or adjusted body weight in participants with obesity) as per the European Society for Clinical Nutrition and Metabolism guidelines [28]. Participants who have additional nutritional support needs (ie, malnutrition or nutrition-impact symptoms: early satiety, altered bowels, nausea, and loss of appetite), will have further individualized nutrition support and have education as a standard of care as determined by the dietitian and their clinical team. Nutrition support after surgery will be determined by the clinical team as per standard practice.

Participants will be contacted weekly by phone or in person, associated with gym visits, by a cancer nurse specialist to provide support promoting adherence to the exercise and nutritional interventions, reassurance, and to enable participants to discuss any concerns about their upcoming surgery. Participants who are smokers will be strongly encouraged to stop smoking. Sessions are based on semistructured questions developed in association with an experienced oncology clinical psychologist. See Multimedia Appendix 1 for further details. Participants could be referred to a clinical psychologist according to the standard of care if the cancer nurse specialist believed it was required.

Participants will complete an investigator-developed satisfaction survey at completion of the intervention prior to surgery (1-4 days before hospital admission or surgery) and 30 days after surgery (±7 days). A qualitative semistructured exit interview will be conducted 24-48 hours prior to hospital discharge and at 30 days after surgery, by an independent researcher face-to-face or over the phone in a subset of participants.

Surgical ward nurses will be requested to complete a survey before the prehabilitation intervention begins and after the completion of the study. Clinical specialists (surgeons and anesthetists) will be requested to complete a web-based evaluation survey after completion of the study.

Data will be collected at 3 assessment times: baseline, before surgery (1-4 days before hospital admission or surgery), and 30 days (±7 days) after surgery assessment. Additional data will be collected during the participant’s hospital stay. Table 2 gives an overview of all assessments and measurements. The primary end point is related to implementation based on the RE-AIM evaluation framework (Table 1) and will be reported using the following dimensions:

The secondary end points collected are outlined in Table 2.

Other exploratory end points include the following:

Assessments and interventions were initially designed to be conducted face-to-face. In response to the COVID-19 pandemic, local lockdowns, reduction in nonurgent face-to-face health care, and cancellation of nonurgent elective surgery with decreased surgery activity, face-to-face recruitment, and intervention delivery were paused in March 2020. The study protocol was adapted to use digital technologies and telehealth methods, and recruitment was recommenced in August 2020. Textbox 2 highlights the key changes.

Participants will be given a unique study number. Deidentified information will be entered into a password-protected project specific Research Electronic Data Capture Database (Vanderbilt University) at Concord Cancer Centre, Concord Repatriation General Hospital. Identifiable information will be stored in a standalone instrument within the Research Electronic Data Capture database and access restricted to a limited number of the research team. In addition, deidentified raw body composition data will be stored on a copy of the manufacturer’s secure password-protected computer software (Seca) at the Concord Cancer Centre, Concord Repatriation General Hospital.

Surgery remains the standard curative treatment for early-stage CRC and UGI cancers. Despite advancements in surgical practices and postoperative care pathways, morbidity and mortality rates remain high [6,7,10]. A reduction in postoperative complications is important. It is well established that the number and severity of postoperative complications are associated with preoperative health status, functional capacity, nutritional status, and muscle strength [44]. While traditional approaches have focused on lifestyle modifications in the postoperative period, recent evidence shows that the preoperative period may be the more appropriate time to intervene [45].

Positive lifestyle practices, including exercise and nutrition, are associated with many health benefits and have been shown to decrease the risk of several common cancers, including CRC and some UGI cancers, and possibly to decrease the risk of cancer recurrence [46,47]. However, only approximately 20% of people diagnosed with cancer are meeting the current exercise guidelines [48-50], and only 37% of patients with gastrointestinal cancer undergo nutrition screening and are offered preoperative nutrition support [51,52]. Recent reviews indicate that optimizing functional capacity with exercise, nutrition interventions, and psychological support strategies in a gastrointestinal surgical population resulted in reduced complications, length of hospital stay, and improved QOL [13-17]. However, few studies have evaluated the integration of prehabilitation practices into standard of care.

This pragmatic prehabilitation program will deliver integrated care, increasing patients’ self-management skills to support healthy living during and after a cancer diagnosis. It has the potential to change standard care with a simple, safe, relatively inexpensive coordinated intervention that confers multiple physical and psychological health benefits. This study will determine whether a multimodal (exercise, nutrition intervention, and nursing support) prehabilitation program can be integrated into routine standard care and whether it improves outcomes by reducing postoperative complication rates and length of stay at the hospital. Unique data will be collected on physical activity, nutritional status, dietary intake, and psychological well-being and their influence on surgical outcomes to inform the current evidence base in gastrointestinal surgical oncology preoperative care.

Prehabilitation adapted to include a telehealth model of care represents a strategy to combat pandemic-related patient and health system challenges. Telehealth initiatives provide an opportunity to minimize health inequalities [53] and improve patient outcomes and access to health care services [54] by offering an alternative delivery method that is not bound by location, especially for those living remotely, or those who have travel difficulties, caregiver or work commitments, or conflicting medical appointments. While telehealth interventions can vary from live consults, electronic monitoring, questionnaires, and support using multimedia platforms, the benefits of education sessions conducted by telehealth have shown to improve the patient’s knowledge and satisfaction during cancer treatment [55]. While the evidence in the preoperative setting is limited [56,57], preliminary findings indicate that home-based prehabilitation programs delivered by telehealth are positively received by patients and clinicians.

The hospital system is complex. Engagement from clinicians, administrative personnel, and participants is crucial to the successful implementation of a multimodal intervention. Importantly, the results of this study will identify priority areas regarding the value and feasibility of integrating prehabilitation into routine quality cancer care for patients undergoing major cancer surgery. It has the potential to improve the outcomes of patients undergoing resection for CRC and UGI cancer and deliver better health at a low cost to the Australian and wider communities.

Prehabilitation represents an opportunity to intervene, treat, and prevent physiological and nutritional decline before major gastrointestinal cancer surgery by combining physical, nutritional, and psychological interventions in a multimodal approach. The study will provide new evidence on the integration of prehabilitation into standard care using adaptive models of health care delivery including telehealth, with the secondary aim of improving postoperative outcomes. The intervention could be generalizable to other types of cancer, emphasizing the importance of preoperative optimization to mitigate the surgical stress response and improve patient outcomes. The study outcomes have the potential to change standard care, with a relatively inexpensive intervention delivered either face-to-face or by telehealth especially for those living remotely or with travel or social difficulties, which can improve health-related quality of life and reduce health care costs.