Colorectal cancer (CRC) is the third most common cancer in the world and the second leading cause of cancer death globally, and is an important component of morbidity and mortality in the global population (1). The International Agency for Research on Cancer (IARC) reported (2) that in 2020 there were 1,932,000 new cases of CRC diagnosed globally, of which 930,000 will die. Unfortunately, 3.2 million new cases and 1.6 million deaths from CRC are expected annually by 2040, with the incidence increasing in younger people. Despite the fact that countries are actively promoting surgery-based comprehensive treatment modalities and have achieved some success, the morbidity and mortality rates of CRC remain high globally (3). The prevention and treatment experiences of some developed countries indicate that current CRC prevention strategies rely mainly on early screening and diagnosis, improvements in lifestyle and the environment, and polypectomy and aspirin administration, whereas CRC treatment modalities include surgery, chemotherapy, radiotherapy and immunotherapy (4). However, colorectal cancer surgical patients usually suffer from preoperative malnutrition, wasting and decreased fitness, and even cachexia and sarcopenia, all of which have been shown to be associated with poor clinical outcomes (5). In addition, surgical trauma triggers a series of metabolic changes in the body, including hormonal, hematologic, metabolic, and immunologic changes, a process known as surgical stress. The aim of prehabilitation is to optimize the various risk factors present in the patient during the preoperative waiting period and to improve the patient’s preoperative physiological and metabolic reserve to better withstand the trauma of surgery, reduce the incidence of perioperative complications and mortality, and optimize the patient’s clinical outcome (6).

Multimodal prehabilitation has been widely used in cancer patients, with initial preoperative rehabilitation focusing on a single exercise regimen to improve the patient’s functional reserve, followed by the addition of nutritional interventions to correct existing nutritional problems, and to help mitigate the patient’s perioperative trauma-related catabolic damage (7). Finally, psychological interventions were introduced to improve adherence to the treatment regimen while enhancing the patient’s intrinsic drive for exercise and nutritional interventions (8). Thus, a well-established multimodal prehabilitation program consists of three components: exercise, nutritional interventions, and psychological interventions, which can also be added to ameliorate poor lifestyles and anemia, among others. Despite the existence of a large body of data on multimodal prehabilitation programs, significant heterogeneity remains for each part of the intervention program, which has an important influence on further analysis.

Although the understanding of preoperative multimodal prehabilitation for rectal cancer is incomplete, the current growing body of clinical evidence gives us confidence in the future. This review will summarize the impact of multimodal prehabilitation on current clinical practice on the basis of the evidence for its plausibility and speculate on directions for further development.

The PRISMA Extension Framework for Scoping Reviews (PRISMA-ScR) checklist was adopted in our study (9).

The initial search yielded a total of 402 documents. After removing duplicates, 284 papers remained. Of which 265 papers were excluded because their abstracts did not satisfy the inclusion criteria of “clinic trial”, “available in English”, and “multimodal prehabilitation”. After that, 19 articles were subjected to full-text review because the abstracts could not be ascertained to be eligible. Subsequently, 9 articles were omitted for the following reasons: repeated, study protocol, full text unavailable and inappropriate topics. Ultimately, a collection of 10 studies was included in this review. Figure 1 displays the literature review process. All of them were published between 2017 and 2024. Most of the studies were originally from Canada (n = 4), Denmark (n = 1), the Netherlands (n = 2), Australia (n =1) or International multicenter (n=2). In addition, there are seven RCTs, a pilot intervention study, a cohort study and an emulated target trial design. Table 2 shows the characteristics of the studies included in this review.

The 10 studies included in this review described multimodal prehabilitation programs for patients undergoing elective CRC surgery, including exercise, nutrition and psychological intervention, which demonstrated that implementation of multimodal prehabilitation, has clinical benefits for CRC patients, such as reducing the incidence of postoperative complications and improving prognosis. However, due to the heterogeneity of multimodal prehabilitation programs in each study, this interferes with further standardized assessment of outcomes (34).

Initial preoperative rehabilitation is dominated by a single preoperative exercise intervention, typically consisting of aerobic, resistance and respiratory training aimed at improving patients’ preoperative functional reserve (35–37). Preoperative aerobic exercise is beneficial in reducing the risk of postoperative complications in patients undergoing major abdominal surgery, and patients with low fitness have a higher rate of postoperative complication morbidity and mortality, with increased cardiorespiratory-related complications being particularly pronounced (38, 39). Currently, the World Health Organization recommendations for the adult population are 150–300 min of moderate-intensity physical activity per week, 75–150 min of vigorous-intensity physical activity, or an equivalent combination of moderate-intensity and vigorous-intensity aerobic exercise (40). Exercise interventions should be presented in the form of an exercise prescription, which usually follows the “FITT” principle, i.e., it should include frequency, intensity, duration, type of exercise and precautions (23). However, the exercise interventions currently implemented do not satisfy the “FITT” principle, and the amount of exercise needs to be standardized, individualized for each patient, and captured and analyzed via lightweight e-health technology to facilitate the achievement of daily goals (41).

The role of nutritional interventions in the multimodal prehabilitation of CRC patients is not only to correct long-standing nutritional problems but also to alleviate the catabolic damage associated with the patient’s perioperative trauma (42). Additionally, adequate protein supplementation in an exercise intervention program is a goal of nutritional intervention, which facilitates muscle strength and improves functional reserve, improving clinical outcomes in patients with CRC (43). Patients who undergo major abdominal surgery are often malnourished because of reduced food intake and metabolic disruption caused by the cancer or tumor itself. Malnutrition, in turn, can lead to weakened physical function, which in turn increases complication rates, and readmission rates, prolongs hospitalization, and surgical recovery time, and decreases quality of life (44). The American Association for Accelerated Rehabilitation and the Perioperative Quality Advancement Consortium recommend that all patients undergoing elective abdominal surgery should be considered for preoperative immunonutritional intervention and that immunonutritional preparations should be administered 5 to 7 days before surgery (25). Nutritional interventions require periodic measurement of outcomes or indicators by the interventionist to assess the appropriateness of the nutritional prescription, so that adjustments can be made if the nutritional prescription does not adequately meet or exceeds the patient’s needs.

Psychological prehabilitation plays an important role in the preoperative multimodal prehabilitation of patients with CRC, alleviating preoperative anxiety while enhancing patients’ intrinsic drive for exercise and nutritional interventions, and improving adherence to regimens (45). Notably, although psychological interventions are recognized in the definition of the multimodal prehabilitation concept, this component is lacking in most current clinical intervention studies (46). Studies that have included psychological interventions in multimodal prehabilitation also suffer from inadequate descriptions, poor reporting of adherence, and substantial heterogeneity in duration and related outcome measures. In addition, with only a few studies risk-stratifying psychology, individualized coping strategies are missing, which contributes to heterogeneity (8).

There is heterogeneity in the evaluation indicators of the effects of multimodal prehabilitation between studies, which affects our further analysis, but also provides us with a direction of thinking. In the functional assessment of the included studies, the 6MWD was one of the most commonly used indicators. This index can simply reflect the basic functional reserve of the patient, the operation is simple, and it is also a method of exercise in the evaluation process. In addition, weekly aerobic and anaerobic exercise is an important part of multimodal prehabilitation, and the assessment of lung function should be increased, which is also the concept of pulmonary rehabilitation and may be associated with postoperative lung infection (47). The PG-SGA is relatively widely used in nutritional assessment, whereas the other indicators are related mainly to blood biochemistry and body composition measurements, however, these indicators have been used in only a few studies (14, 22). Future studies may use them to quantify nutrition-related outcomes, which is especially important for CRC patients.

Patient compliance in multimodal prehabilitation is a concern, especially in the unsupervised setting (48). In general, patients with CRC have 4 to 8 weeks of preoperative time to receive multimodal prehabilitation interventions at healthcare facilities, in the community, or at home. Prehabilitation is usually implemented under the supervision of healthcare professionals, and face-to-face and supervised forms of prehabilitation are considered the gold standard for implementing prehabilitation (49). Home-based prehabilitation is considered to have better implementation outcomes and higher levels of participation. The advantages of home-based prehabilitation programs include convenience and low cost, whereas the disadvantages include that compliance may be compromised for more severely ill patients and those who lack in-hospital supervision. The place of implementation depends on the patient’s preference and the availability of health resources, and regardless of the place of implementation of the program, it is necessary to assess patient adherence and provide reinforcement through regular feedback. With the advancement of technology and the widespread use of e-health technology in healthcare, patients can be supervised for home training through the use of tele-rehabilitation modalities such as video conferencing (16). Wearable devices can also be used to enable mutual understanding and feedback between patients and healthcare providers, which is a promising approach to improving adherence (50).

This review demonstrates the current evidence of multimodal prehabilitation in patients undergoing colorectal cancer surgery, showing a positive impact and beneficial trend on patient clinical outcomes. However, owing to the heterogeneity of multimodal prehabilitation in terms of specific content, duration, and evaluation metrics, many high-quality trials by researchers are still needed to explore the optimal model of multimodal prehabilitation and promote its standardization.