Abstract
Background:
The surgical intervention serves as the paramount and prevalent remedy for individuals afflicted with colorectal malignancies, with the significance of perioperative stewardship and convalescence being indisputable. Prehabilitation coupled with preoperative lifestyle modulation has demonstrated efficacy in patients subjected to certain classifications of abdominal procedures. However, the evidence pertaining to its impact on those battling colorectal cancer remains equivocal.
Methods:
A meta-analysis, grounded in pairwise contrast, of randomized controlled trials (RCTs) was orchestrated, coupled with a systematic review, to probe the efficacy of preoperative lifestyle modulation and prehabilitation on patients’ postoperative functionality and recuperation. An exhaustive exploration of 8 electronic databases and trial registries was undertaken to encompass all pertinent RCTs disseminated in English or Chinese from January 2012 through December 2022. Employing a random-effects model, we evaluated parameters such as the 6-minute walk test (6 MWT), complications, quality of life (QoL), aggregate and postoperative duration of hospitalization (tLHS and postLHS), and healthcare expenditure (HExp) for postoperative patients.
Results:
A total of 28 RCTs were incorporated into the systematic review and meta-analysis. Relative to conventional preoperative care, rehabilitation or preoperative lifestyle management was found to enhance postoperative 6MWT (SMD 1.30, 95% CI 0.30 to 2.29) and diminish the complication rate (OR 0.53, 95% CI 0.40 to 0.69). Nonetheless, no significant discrepancies were observed in QoL (SMD 1.81, 95% CI −0.26 to 3.87), tLHS (SMD −0.26, 95% CI −0.68 to 0.15), and postLHS (SMD −1.46, 95% CI −3.12 to 0.20) between the groups. HExp could not be evaluated due to a lack of sufficient data for synthesis. Most pooled outcomes exhibited significant heterogeneity, urging a cautious interpretation. Subgroup analysis revealed that nutritional interventions could mitigate the incidence of complications, and preoperative exercise could improve tLHS and postLHS. A combined approach of physical, nutritional, and psychological intervention or prehabilitation proved superior to any single intervention in enhancing postoperative capabilities.
Conclusion:
This meta-analysis delineated the efficacy of preoperative interventions on postoperative capabilities in patients with colorectal cancer, thereby offering evidence for clinical practice. It was concluded that preoperative interventions are unequivocally beneficial for postoperative functional recovery and the reduction of complication rates in patients with colorectal cancer. Nonetheless, the acquisition of more high-level evidence is still necessitated to further ascertain the effectiveness of this strategy for other patient groups and to establish its best practices. The heterogeneity in the pooled outcomes underlines the need for future studies to be more uniform in their design and reporting, which would facilitate more robust and reliable meta-analyses.
Keywords: colorectal neoplasms, prehabilitation, lifestyle management, preoperative exercise, perioperative care
Introduction
Colorectal cancer (CRC) is one of the most prevalent malignant neoplasms, responsible for approximately 11% of all cancer diagnoses worldwide and leading to 8.8 million deaths in 2018. 1 Over the past decade, an increase in CRC cases has been observed among individuals under 50, particularly in countries undergoing economic transitions, thereby escalating healthcare expenditures.1 -3 Surgical treatment, either via laparoscopic or open abdominal operations, is typically the preferred approach for most CRC cases, especially those in the early stages, when simple endoscopic treatment is not feasible. The choice between laparoscopic and open surgery largely depends on the surgeon’s expertise and the patient’s condition. 4 Therefore, the perioperative care of CRC patients is of paramount importance, with potential implications for surgical outcomes and prognoses.5,6 Beyond routine perioperative care, the Enhanced Recovery After Surgery (ERAS) protocol has emerged as one of the most employed strategies in the surgical management of CRC.7,8 A typical ERAS strategy often emphasizes the importance of preoperative management, but it primarily focuses on the postoperative phase. 9
In 2015, prehabilitation emerged as a complementary and potentially more efficacious strategy than ERAS, 10 aimed at augmenting postoperative functional capacities. This innovative concept in preoperative management serves as an extension of ERAS principles, wherein patients undergo interventions prior to the surgical stress. These interventions encompass cardiorespiratory conditioning primarily through aerobic and resistance exercises, nutritional support mainly through the supplementation of whey protein, and psychological assistance. 11 The effectiveness of prehabilitation has been demonstrated in diverse patient populations undergoing surgical treatments. Prehabilitation adopts a proactive approach to enhance the patient’s health and physical condition prior to surgery, with the ultimate goal of fortifying their ability to endure the stress of the procedure and expedite their recovery thereafter. 12
Typically, a prehabilitation approach encompasses 3 components: preoperative physical exercise, nutritional support, and cognitive intervention. 13 In essence, it is a preoperative lifestyle intervention that focuses on enhancing the functional capacity of patients. 11 Prehabilitation has proven effective in certain types of surgeries, particularly lung cancer and abdominal malignancy surgeries, with a multimodal prehabilitation approach often favored over a single preoperative lifestyle intervention.12,14 -16 However, there is a dearth of high-level evidence regarding the effectiveness of prehabilitation in CRC patients. The current evidence from randomized controlled trials (RCTs) is mixed, especially when considering studies from different regions. The practical application of prehabilitation in clinical settings also remains to be fully explored.
Perhaps due to the novelty of the prehabilitation concept, it has been referred to by various terms such as preoperative intervention and capacity improvement before surgery.13,17 This has resulted in a dispersion of related evidence, making it more challenging for clinical practice to reference. Furthermore, the specific role and impact of each component within prehabilitation in enhancing a patient’s capacity requires further investigation. Therefore, in this context, this study aims to provide evidence on the effectiveness of prehabilitation and other forms of preoperative lifestyle interventions on postoperative capability in CRC patients.
Methods
Study Design
This systematic review of randomized controlled trials used contrast-based frequentist pairwise meta-analysis to synthesize data. We reported the results according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement. 18 A protocol was prepared and registered a priori in PROSPERO (CRD42022359495).
Eligibility Criteria
We aimed to include all randomized controlled trials related to prehabilitation and preoperative lifestyle interventions in patients with CRC in the past 10 years. The eligibility criteria are displayed in Table 1.
Table 1.
Eligibility Criteria.
| Inclusion | Exclusion | ||
|---|---|---|---|
| Type | Criteria | Type | Criteria |
| P | adults (aged 18 y old or above) with colorectal cancer, comprising colon cancer, rectal cancer, sigmoid cancer, cecal cancer, or appendiceal cancer of any TNM classifications and in planned surgery, or preoperative status. | P | cTNM stage IVb patients who received palliative surgery |
| I | Prehabilitation or preoperative lifestyle intervention of any types, including any one in or any combination of nutritional intervention (counseling), physical training, and psychological support. | I | Any imbalance of postoperative care between interventional and control groups |
| C | Regular routine perioperative care | ||
| O | Primary outcome: (1) postoperative 6-minute walk test (6MWT) result; Second outcomes: (2) postoperative quality of life (QoL) scores reported as any validated QoL scales; (3) postoperative complication, reported as proportions (cases) or any validated scales (e.g., comprehensive complication index 19 ); (4) total length of hospital stay (tLHS); (5) postoperative length of hospital stay (postLHS); (6) health expenditure (HExp), reported as the expense of the hospital stay in any currency |
Other | Trial not completed or data not available from the investigators |
| S | Randomized controlled trials (RCT) | ||
| Other | Language: English or Chinese Publication date: from 1 Jan 2012 to 15 December 2022 |
||
Search Strategy
We searched PubMed, Web of Science, Embase, CINAHL, Cochrane Central Register of Controlled Trials, CNKI, WanFang Data, and SinoMed for eligible articles published from 1 January 2012 to 15 December 2022 using terms “colorectal,” “colon,” “rectal,” “prehabilitation,” “lifestyle,” “nutrition*,” “exercise,” “psychologi*,” “congnition*,” and others. The full and detailed search strategy can be found in File S1.
Screening, Selection and Data Extraction
All references identified from the search were imported into EndNote 20 (Clarivate, PA, USA) to remove duplicates. After automatic exclusion by filtering title using excluding terms, the reviewers (J.-J.Z., Y.-R.H., H.-L.D., and Z.-M.H.) assessed the eligibility in the order of title, abstract, and full text. Each reference was decided independently by at least 2 reviewers, and arisen discrepancies were discussed and decided by the authors together.
Four reviewers (J.-J.Z., Y.-R.H., H.-L.D., and Z.-M.H.) independently extracted data using a standard data collection form. We resolved any disagreements by discussion and consensus.
Risk of Bias Assessment
Two reviewers independently assessed risk of bias of the included studies using Cochrane RoB 2 tools. 20 RCTs were categorized into the levels of “low,” “some concerns,” or “high” risk of bias based on the level of 5 different domains of risk of bias in RoB 2 tools.
Statistical Analysis
Primarily, we employed the “metafor” package within R for our data synthesis. A frequentist method rooted in pairwise contrast was utilized for the meta-analysis, with heterogeneity evaluated through I² and Q statistics. In instances where the I² statistic exceeded 50%, a random-effects model was applied in the meta-analysis, while a fixed-effect model was otherwise implemented. To further analyze heterogeneity, we conducted a subgroup analysis based on the characteristics of the participants and the types of interventions. Sensitivity analyses were carried out to gage the robustness of our results. The presence of publication bias was assessed using the Begg and Egger tests. For this study, the level of statistical significance was set at 0.05, two-tailed.
The collated data were presented as the standardized mean difference (SMD) for continuous data measurements, odds ratio (OR) for dichotomous data, and SMD for outcomes reported in both continuous and dichotomous formats. Additionally, 95% confidence intervals (95% CI) were disclosed.
Results
Study Characteristics
We identified 2620 publications and trial registrations from the initial search. After data selection, 28 studies were finally included in the review (Figure 1). The study characteristics were displayed in Table 2.
Figure 1.
PRISMA flow diagram of study selection.
Table 2.
Study Characteristics.
| Study | Origin | Treatment | Duration | Interventional group | Control group | Outcomes | Risk of bias | ||
|---|---|---|---|---|---|---|---|---|---|
| Size | Age | Size | Age | ||||||
| Berkel et al 21 | Netherlands | E | 3 wk | 28 | 74.0 ± 7.00 | 29 | 73.0 ± 6.00 | ②(+)④(+) | SC |
| Burden et al 22 | UK | N | 3 wk | 45 | 70.5 ± 11.7 | 45 | 68.9 ± 11.5 | ④(+) | SC |
| Carli 2020 [23] | USA | N + E+P | 4 wk | 55 | 77.3 ± 7.61 | 55 | 80.2 ± 6.85 | ①(-)③(-)④(-) | SC |
| Chen et al 23 | China | N | 3 d | 30 | 58.4 ± 14.6 | 30 | 58.1 ± 15.2 | ④(-) | SC |
| Chen 2015 24 | China | N | 5 d | 28 | 74.0 ± 2.00 | 28 | 75.0 ± 3.00 | ②(+)④(+) | SC |
| Chen 2020 25 | China | N + E+P | NR | 36 | 58.4 ± 2.27 | 36 | 58.4 ± 2.27 | ①(+) | SC |
| Cheng 2014 26 | China | N | NR | 35 | NR | 35 | NR | ④(+) | SC |
| Gillis 2014 27 | Canada | N + E+P | 4 wk | 38 | 65.7 ± 13.6 | 39 | 66.0 ± 9.10 | ①(+)④(-)⑤(-) | L |
| Gloor et al 28 | Switzerland | E | 3 wk | 54 | 59.6 ± 50.3 | 53 | 59.7 ± 43.4 | ③(-)④(-) | L |
| He et al 29 | China | N | NR | 36 | NR | 34 | NR | ④(+) | H |
| Li 2021 30 | China | N + E+P | 2 mo | 39 | 46.3 ± 5.13 | 39 | 46.3 ± 5.07 | ③(+)④(+)⑤(+) | H |
| Loughney 2021 31 | UK | E | 9 wk | 12 | 64.0 ± 14.0 | 11 | 57.0 ± 10.0 | ⑤(+) | SC |
| Ma 32 | China | N | 2 d | 47 | 59.6 ± 3.46 | 46 | 59.6 ± 3.46 | ④(+) | H |
| Northgraves 2020 33 | UK | E | 10 wk | 10 | 64.1 ± 10.5 | 11 | 63.5 ± 12.5 | ①(+)③(+) | L |
| Ommundsen et al 34 | Norway | N | 3 wk | 63 | 78.2 ± 7.40 | 53 | 78.8 ± 7.80 | ④(-) | SC |
| Onerup 2022 35 | Sweden | E | 2 wk | 317 | 69.0 ± 11.0 | 351 | 68.0 ± 11.0 | ②(-)④(-) | L |
| Peng et al 36 | China | E | 2 wk | 109 | 63.0 ± 2.80 | 104 | 62.8 ± 3.10 | ②(-)④(-) | L |
| Qin et al 37 | China | E | 5 d | 100 | 63.9 ± 12.6 | 100 | 63.7 ± 12.6 | ②(+)③(+)④(+) | H |
| Shen et al 38 | China | N | 3 d | 80 | 66.9 ± 4.05 | 80 | 65.0 ± 4.35 | ③(+)④(+) | SC |
| Tian et al 39 | China | P | 3 d | 78 | 60.5 ± 5.44 | 78 | 61.1 ± 5.35 | ②(+) | SC |
| Wang and Pan 40 | China | E | 1 wk | 150 | 62.2 ± 8.46 | 150 | 62.2 ± 8.46 | ③(+)④(+) | SC |
| Wang 2022 41 | China | N + E+P | NR | 80 | 73.3 ± 6.47 | 80 | 71.3 ± 8.42 | ①(-)②(+)③(-)④(-) | SC |
| Yan 2020 42 | China | N + E+P | 2 wk | 20 | 69.6 ± 2.72 | 20 | 69.5 ± 2.78 | ①(+)④(+) | SC |
| Yan 2021 43 | China | N + E+P | 4-8 wk | 40 | 67.6 ± 4.09 | 40 | 67.6 ± 4.09 | ①(+)②(+)④(-) | SC |
| Zhang 2019 44 | China | N | NR | 50 | 58.6 ± 2.80 | 50 | 58.5 ± 2.90 | ④(-)⑤(+) | SC |
| Zhang and Zhou 45 | China | N | 1 d | 70 | 63.0 ± 7.81 | 70 | 62.3 ± 8.04 | ②(+)④(+) | SC |
| Zhu 2015 46 | China | N | 3 d | 47 | 53.5 ± 6.00 | 46 | 53.1 ± 4.80 | ②(+)④(+) | SC |
| Zhu 47 | China | N | 3 d | 32 | 57.3 ± 4.20 | 32 | 57.3 ± 4.20 | ④(+) | SC |
Abbreviations: N, nutritional intervention; E, physical exercise; P, psychological support; NR, not reported; L, low risk of bias; SC, some concerns; H, high risk of bias.
For outcomes reported: ①, 6MWT results; ②, postLHS; ③, tLHS; ④, complications; ⑤, QoL; (+): Pre-rehabilitation proves efficacious; (-) Pre-rehabilitation proves ineffective.
The bulk of the trials were disseminated within the past 5 years (2018-2023), with China serving as the primary source. The sample sizes spanned a spectrum from a mere 10 to a substantial 317, with the majority of participants being individuals of advanced age, exceeding 60 years. Given the absence of a standardized method for prehabilitation or lifestyle management, the selected interventions diverged across studies, and participants underwent varying durations of preoperative treatment, ranging from a single day to an extensive 9 weeks. Among the predetermined outcomes, health expenditure failed to be reported by the qualifying studies and thus was omitted from the final analysis.
Risk of Bias
Out of the 28 studies incorporated into our analysis, 4 studies (14%) were identified as carrying a high risk of bias, while 6 studies (21%) were deemed to bear a low risk of bias (as shown in Figure 2). The overall risk of bias in the eligible studies was deemed acceptable. The risk of bias assessment results for each included study are presented in Table 2.
Figure 2.
Risk of bias assessment.
Primary Outcomes
Six-minute walk test
Seven studies,25,27,33,41 -43,48 encompassing 560 participants, reported results for the postoperative 6-minute walk test (6MWT). In these studies, a combination of nutritional, exercise, or psychological interventions was employed by 6 of them. The pooled analysis indicated that prehabilitation and/or preoperative lifestyle management significantly enhanced the patients’ postoperative activity capability compared to routine care (SMD = 1.30, 95% CI 0.30 to 2.29). However, substantial heterogeneity was observed (as depicted in Figure 3A).
Figure 3.
Effect of prehabilitation on 6WMT. (A) pooled analysis. (B) sensitive analysis, omitting each single study, random-effect model. (C) sensitive analysis, adding each single study, fixed-effect model. (D) subgroup analysis of studies of different origin. (E) subgroup analysis of different interventional duration.
In this analysis there was no significant publication bias on Egger test (P = .065). A sensitivity analysis was performed, and the results were not significantly different from the total combined estimated value, which suggested that the meta-analysis results were relatively stable and reliable. Subgroup analysis revealed that the Chinese studies, which did not report their duration of intervention, contributed most to the observed heterogeneity (as shown in Figure 3D and E). Despite this, the result remained robust when any single study was omitted from or added to the pooled analysis, as well as when different models were utilized (as illustrated in Figure 3B and C).
We observed that when only non-Chinese research data were available, the heterogeneity was 0. The pooled analysis showed that prehabilitation and/or preoperative lifestyle management significantly improved the patients’ postoperative activity capability compared to routine care (SMD = 0.46, 95% CI 0.19 to -0.74), and the results were stable. (as shown in Figure 4).
Figure 4.
Sensitivity analysis of 6-minute walk test (6WMT) results from western studies only.
Postoperative complications
Twenty-two investigations, encompassing 2989 participants, documented postoperative complications. The amalgamated analysis suggested that prehabilitation or preoperative lifestyle modifications could efficaciously diminish the occurrence of postoperative complications (OR = 0.43, 95% CI 0.40 to 0.69, Figure 5A), accompanied by a moderate, yet acceptable, heterogeneity (I2 = 51%). Subgroup Analysis by Country: heterogeneity was not reduced, indicating country is not the source of heterogeneity. Subgroup scrutiny inferred that both a multimodal intervention and standalone nutritional counseling could yield effective reductions in complications, with the latter demonstrating a larger effect size (Figure 5A). Sensitivity scrutiny pinpointed Onerup 2022 35 as a potential heterogeneity source, yet the amalgamated outcome remained fairly robust when excluding or incorporating a single study (Figure 5C and D). A sensitivity analysis was performed, and the results were not significantly different from the total combined estimated value, which suggested that the meta-analysis results were relatively stable and reliable.
Figure 5.
Effect of prehabilitation on postoperative complications. (A) pooled analysis and subgroup analysis of different treatment types. (B) Funnel Plot, an evaluation of publication bias. (C) sensitive analysis, omitting each single study, random-effect model. (D) sensitive analysis, adding each single study, fixed-effect model. (E) subgroup analysis of different intervention duration.
Abbreviations: N, nutritional intervention; E, exercise; P, psychological support; NEP, combination of nutritional, exercise, and psychological interventions.
Secondary Outcomes
Quality of life
A mere quartet of investigations27,30,31,44 proffered accessible Quality of Life (QoL) findings, utilizing disparate scales. No discernible distinction was observed between the intervention and control cohorts (SMD = 1.81, 95% CI −0.26 to 3.87), accompanied by pronounced heterogeneity (I 2 = 97%, P < .01, Figure 6). Sensitivity analysis, subgroup analyses and publication bias could not be performed due to the limited number of included studies.
Figure 6.
Effect of prehabilitation on QoL.
The impacts exhibited marked variation across the individual trials. Owing to the paucity of studies and participants incorporated, a heterogeneity analysis was not undertaken. Ultimately, the amalgamated outcome failed to illuminate the efficacy of prehabilitation on Quality of Life.
Postoperative length of hospital stay
A total of 10 studies, comprising 1823 participants, were amalgamated for the analysis of post-operative length of hospital stay (postLHS). The meta-analysis revealed no significant effect (SMD = −1.46, 95% CI −3.12 to 0.20, Figure 7A), and substantial heterogeneity was still apparent (I² = 96%, P < .01). A subgroup analysis of different treatment strategies suggested that the heterogeneity might primarily stem from trials that solely employed nutritional counseling as an intervention. When these RCTs were excluded, the effect attained significance (Figure 7B). However, the results were not consistently robust when a specific study 46 was omitted and also fluctuated between models (Figure 7C and D). Publication bias was assessed by Egger test and significant statistical publication bias was detected (P = .04). Sensitivity analysis was performed and demonstrated that one study might have been highly influential, suggesting that this result may be an outlier. 46
Figure 7.
Effect of prehabilitation on postLHS. (A) pooled analysis and subgroup analysis for different intervention strategies. (B) pooled analysis excluding nutritional intervention-only trials. (C) sensitive analysis, omitting each single study, random-effect model. (D) sensitive analysis, adding each single study, fixed-effect model.
Abbreviations: N, nutritional intervention; E, exercise; P, psychological support; NEP, combination of nutritional, exercise, and psychological interventions.
Total length of hospital stay
Total length of hospital stay (tLHS) was reported in 8 studies. Of these, 3 implemented multimodal interventions (nutritional, exercise, and psychological), while 4 only used exercise as an intervention. The pooled analysis did not reveal a significant difference between the groups (SMD = −0.26, 95% CI −0.68 to 0.15, Figure 8A), but there was relatively high heterogeneity (I² = 89%). Heterogeneity analysis suggested that trials which only used exercise as an intervention appeared to be more homogenous, and a positive effect was observed in the pooled analysis of these trials (SMD = −0.29, 95% CI −0.45 to −0.13, Figure 8A). Sensitivity analysis did not identify a single study that could account for the heterogeneity (Figure 8B and C). In this analysis there was no significant publication bias on Egger test (P = .9313). Sensitivity analysis was performed and demonstrated that one study might have been highly influential, suggesting that this result may be an outlier. 41
Figure 8.
Effect of prehabilitation on total length of hospital stay. (A) pooled analysis and subgroup analysis of different treatment types. (B) sensitive analysis, omitting each single study, random-effect model. (C) sensitive analysis, adding each single study, fixed-effect model.
Abbreviations: N, nutritional intervention; E, exercise; P, psychological support; NEP, combination of nutritional, exercise, and psychological interventions.
Discussion
This systematic review assembled and consolidated the current body of evidence regarding the influence of prehabilitation or preoperative lifestyle interventions on postoperative performance in colorectal cancer patients. On the whole, the postoperative physical capability, as measured by the 6WMT, as well as the incidence of complications, could be effectively lessened by these interventions. However, we did not observe a significant improvement in LHS and QoL, primarily due to the limited sample size and significant heterogeneity.
Prior to the introduction of the concept of prehabilitation, 10 there were already studies that implemented preoperative interventions and observed positive outcomes, such as the use of nutritional strategies to prevent postoperative malnutrition.24,26,46 However, these studies primarily adopted a robust nurse- or practitioner-led approach and predominantly utilized enteral nutrition as opposed to comprehensive nutritional counseling and food intake recording. The heterogeneity observed may be due to these early studies not adopting prehabilitation as their underlying rationale.
Another prominent source of heterogeneity was the type of treatment. In our analysis, we classified the studies into multimodal groups (comprising nutritional, exercise, and psychological interventions) and groups that only had nutritional, exercise, or psychological interventions. Most of the time, subgroup analysis indicated a significant difference between groups. However, the multimodal group did not appear to be more effective than the groups with a single intervention, especially when compared to the nutritional group. A likely reason inferred from the methods of intervention in the trials was that the nutritional interventions in the latter group were generally more rigorous than those in the multimodal ones. Most included prehabilitation trials employed nutritional counseling as well as exercise advice, while the trials with only one intervention used supervised exercise or enteral nutrition. However, the subgroup analysis did not suggest that the difference was clinically significant. We could not find data on patient compliance with different intervention strategies in the studies, but the appropriateness of the intensity and duration of the intervention should be considered in clinical practice.
In addition to the different combinations of lifestyle strategies, the duration of the intervention and the specific intervention plan (such as a menu or exercise plan) also contributed to the heterogeneity. However, we were unable to explain this via subgroup analysis using the currently available data, because the reporting quality of the included studies was relatively low: some participant characteristics as well as detailed intervention methods were not reported. Nevertheless, some individual studies appeared to be very different in their intervention methods. Also, the duration of the intervention varied greatly, ranging from 1 day to 9 weeks, and the timepoints at which postoperative measurements were recorded also differed. All of these factors could make the outcomes more difficult to interpret and therefore need to be applied with caution.
In our pooled analysis, both the 6-Minute Walk Test (6WMT) results and the incidence of complications were found to be significantly improved in prehabilitation groups, with relatively large effect sizes. The 6WMT is commonly used to assess the physical functional capacity of patients undergoing surgery or those with chronic diseases. 49 Our effect size was similar to that reported in an earlier Cochrane systematic review involving patients with colorectal cancer, which included 3 trials. 50 The 6WMT results of patients with other types of cancer who underwent surgery also improved with prehabilitation. 51 Patients who engaged in pre-operative exercises, such as muscle strength training, endurance training, etc., improved their physical fitness before surgery and therefore recovered faster after surgery.52 -54
The incidence of postoperative complications was also significantly reduced in the prehabilitation groups. However, this should be interpreted with caution, as the definitions and recording procedures for complications varied across different trials. Open-label strategies without blinding could also contribute to bias. Notably, previous studies have reported that exercise under preoperative supervision for abdominal surgery did not reduce the incidence of postoperative complications, 55 and triple prehabilitation did not significantly reduce postoperative mortality and complications in elderly patients undergoing surgery. 56
Postoperative and total Length of Hospital Stay (LHS) were found to be similar between the prehabilitation and control groups, which is consistent with some other publications. 50 However, this contradicts a systematic review published in 2018 that included older trials and cohorts. 57 Perioperative management strategies could be one of the important factors influencing LHS. Some hospitals have a fixed-period hospital stay plan, for example, patients are admitted 2 days before surgery and discharged 1 week postoperatively, regardless of the type of preoperative management. Researcher bias should also be considered in this context.
Although we performed a pooled analysis on Quality of Life (QoL), there were only 4 trials included and these demonstrated significant heterogeneity. Therefore, the effectiveness of prehabilitation on postoperative QoL remains to be explored. Evidence on QoL is also mixed in patients with other diseases undergoing surgeries.58 -60 Researchers continue to design new prehabilitation models for better QoL outcomes, 60 and a standardized prehabilitation intervention may contribute to this.
Limitations
This systematic review has several limitations. First, the heterogeneity of the included studies remains a significant barrier when interpreting the results. Subgroup and sensitivity analyses were performed to analyze probable sources of heterogeneity; however, more detailed participant and intervention information were not reported by the studies, making it impossible to identify all sources of variability. Furthermore, by including some articles published in Chinese journals, our results can more objectively reflect the outcome measures. However, the inclusion of certain Chinese articles with lower quality may also have an impact on our results. Second, reporting bias, including publication bias and selective outcome reporting, may impact the results. The Egger test and funnel plots indicated that publication bias existed for specific outcomes. Furthermore, a few trials were excluded because they did not report specific outcomes, and there was no response from the investigators when we attempted to contact them for this information. Third, meta-regression and statistical adjustment of the effect sizes were not conducted due to insufficient participant characteristic data reported in the studies. This means that potential confounding variables may not have been adequately controlled for in the analysis, which could influence the overall results and conclusions.
Conclusion
This investigation delineates the potency of prehabilitation, or the management of preoperative lifestyle, in patients diagnosed with colorectal cancer. Collectively, prehabilitation can enhance patients’ physical prowess post-surgery and mitigate complication rates. However, the impact on other metrics of functional capability warrants further exploration. Rigorously designed and methodologically robust Randomized Controlled Trials (RCTs) remain a necessity to quantify the influence of prehabilitation. A uniform prehabilitation protocol could be employed by healthcare professionals to bolster the prognosis of patients with colorectal cancer.
Acknowledgments
The authors would like to express deeply grateful to each of the researchers involved in the study, and anyone else who helped in this study.
Footnotes
Author Contributions: All authors have agreed on the final version and meet at least one of the following criteria (recommended by the ICMJE [*http://www.icmje.org/recommendations/]): substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content.
The author contribution box as follows:
| Criteria | Author Initials |
|---|---|
| Made substantial contributions to study design, acquisition of data, or analysis and interpretation of data; | JiaJun Zhang, YuRu Hu, HuiLi Deng |
| Involved in drafting the manuscript or revising it critically for important intellectual content; | JiaJun Zhang, YuRu Qu Shen |
| Given final approval of the version to be published. | JiaJun Zhang, YuRu Qu Shen |
| Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. | JiaJun Zhang, YuRu Hu, HuiLi Deng, ZhongMou Huang, JianMei Huang, Qu Shen |
Data availability statement: All data used in this work are from published materials.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by Humanities and Social Sciences Research Planning Fund of the Ministry of Education (21YJAZH071) and XMU Training Program of Innovation and Enterpreneurship for Undergraduates (2023 × 645).
Ethical Statement: This study was approved by the ethics committee of School of Medicine, Xiamen University on September 14 of 2022. (XDYX202209K22).
Informed consents: This systematic review does not need ethical approval or informed consents from participants.
ORCID iD: JiaJun Zhang
https://orcid.org/0000-0001-6381-8713
References
- 1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. doi: 10.3322/caac.21492 [DOI] [PubMed] [Google Scholar]
- 2. Sinicrope FA. Increasing incidence of early-onset colorectal cancer. New Engl J Med. 2022;386:1547-1558. doi: 10.1056/NEJMra2200869 [DOI] [PubMed] [Google Scholar]
- 3. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14:89-103. doi: 10.5114/pg.2018.81072 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Hashiguchi Y, Muro K, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25:1-42. doi: 10.1007/s10147-019-01485-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Dekker JW, van den Broek CB, Bastiaannet E, et al. Importance of the first postoperative year in the prognosis of elderly colorectal cancer patients. Ann Surg Oncol. 2011;18:1533-1539. doi: 10.1245/s10434-011-1671-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Lassen K, Hannemann P, Ljungqvist O, et al. Patterns in current perioperative practice: survey of colorectal surgeons in five northern European countries. BMJ. 2005;330:1420-1421. doi: 10.1136/bmj.38478.568067.AE [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Ni X, Jia D, Chen Y, Wang L, Suo J. Is the enhanced recovery after surgery (ERAS) program effective and safe in laparoscopic colorectal cancer surgery? A meta-analysis of randomized controlled trials. J Gastrointest Surg. 2019;23:1502-1512. doi: 10.1007/s11605-019-04170-8 [DOI] [PubMed] [Google Scholar]
- 8. Li Q, Du L, Lu L, et al. Clinical application of enhanced recovery after surgery in perioperative period of laparoscopic colorectal cancer surgery. J Laparoendosc Adv Surg Tech A. 2019;29:178-183. doi: 10.1089/lap.2018.0708 [DOI] [PubMed] [Google Scholar]
- 9. Gustafsson UO, Scott MJ, Hubner M, et al. Guidelines for perioperative care in elective colorectal surgery: enhanced recovery after surgery (ERAS®) society recommendations: 2018. World J Surg. 2019;43:659-695. doi: 10.1007/s00268-018-4844-y [DOI] [PubMed] [Google Scholar]
- 10. Carli F, Scheede-Bergdahl C. Prehabilitation to enhance perioperative care. Anesthesiol Clin. 2015;33:17-33. doi: 10.1016/j.anclin.2014.11.002 [DOI] [PubMed] [Google Scholar]
- 11. West MA, Carli F, Grocott MPW. Editorial: personalised multimodal prehabilitation in cancer. Front Oncol. 2022;12:1086739. doi: 10.3389/fonc.2022.1086739 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. López Rodríguez-Arias F, Sánchez-Guillén L, Armañanzas Ruiz LI, et al. A narrative review about prehabilitation in surgery: current situation and future perspectives. Cir Esp. 2020;98:178-186. doi: 10.1016/j.cireng.2020.03.014 [DOI] [PubMed] [Google Scholar]
- 13. Scheede-Bergdahl C, Minnella EM, Carli F. Multi-modal prehabilitation: addressing the why, when, what, how, who and where next? Anaesthesia. 2019;74 Suppl 1:20-26. doi: 10.1111/anae.14505 [DOI] [PubMed] [Google Scholar]
- 14. Avancini A, Cavallo A, Trestini I, et al. Exercise prehabilitation in lung cancer: getting stronger to recover faster. Eur J Surg Oncol. 2021;47:1847-1855. doi: 10.1016/j.ejso.2021.03.231 [DOI] [PubMed] [Google Scholar]
- 15. Gillis C, Davies SJ, Carli F, et al. Current landscape of nutrition within prehabilitation oncology research: a scoping review. Front Nutr. 2021;8:644723. doi: 10.3389/fnut.2021.644723 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Silver JK. Cancer prehabilitation and its role in improving health outcomes and reducing health care costs. Semin Oncol Nurs. 2015;31:13-30. doi: 10.1016/j.soncn.2014.11.003 [DOI] [PubMed] [Google Scholar]
- 17. Minnella EM, Liberman AS, Charlebois P, et al. The impact of improved functional capacity before surgery on postoperative complications: a study in colorectal cancer. Acta Oncol. 2019;58:573-578. doi: 10.1080/0284186X.2018.1557343 [DOI] [PubMed] [Google Scholar]
- 18. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258:1-7. doi: 10.1097/SLA.0b013e318296c732 [DOI] [PubMed] [Google Scholar]
- 20. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898 [DOI] [PubMed] [Google Scholar]
- 21. Berkel AEM, Bonger BongersBC, Kotte H, et al. Effects of community-based exercise prehabilitation for patients scheduled for colorectal surgery with high risk for postoperative complications: results of a randomized clinical trial. Ann Surg. 2022;275:e299-e306. doi: 10.1097/SLA.0000000000004702 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Burden ST, Gibson DJ, Lal S, et al. Pre-operative oral nutritional supplementation with dietary advice versus dietary advice alone in weight-losing patients with colorectal cancer: single-blind randomized controlled trial. J Cachexia Sarcopenia Muscle. 2017;8:437-446. doi: 10.1002/jcsm.12170 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Chen J, Ye J, Song W, et al. [Application of enteral nutrition in preoperative bowel preparation for rectal cancer patients undergoing radical operation]. Zhonghua Weichangwaike Zazhi [Chin J Gastrointest Surg]. 2013;16:1059-1062. doi: 10.3760/cma.j.issn.1671-0274.2013.11.010 [DOI] [PubMed] [Google Scholar]
- 24. Chen Y. [Clinical Studies on Preventive Nutritional Support in Elderly Patients With Rectal Cancer]. Soochow University; 2015. [Google Scholar]
- 25. Chen X, Qiu S. [The effect of pre-rehabilitation measures on neoadjuvant chemotherapy in patients with rectal cancer]. Qilu Huli [J Qilu Nurs]. 2020;26:36-38. doi: 10.3969/j.issn.1006-7256.2020.12.010 [DOI] [Google Scholar]
- 26. Cheng F, Peng G. [Effect of enteral nutrition in intestinal preparation of colorectal cancer surgery]. Changjiangdaxue Xuebao (Zirankexue Ban) [J Yangtze Univ (Natural Science Edition)]. 2014;11:146-149. doi: 10.16772/j.cnki.1673-1409.2014.36.080 [DOI] [Google Scholar]
- 27. Gillis C, Li C, Lee L, et al. Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer. Anesthesiology. 2014;121:937-947. doi: 10.1097/ALN.0000000000000393 [DOI] [PubMed] [Google Scholar]
- 28. Gloor S, Misirlic M, Frei-Lanter C, et al. Prehabilitation in patients undergoing colorectal surgery fails to confer reduction in overall morbidity: results of a single-center, blinded, randomized controlled trial. Langenbecks Arch Surg. 2022;407:897-907. doi: 10.1007/s00423-022-02449-0 [DOI] [PubMed] [Google Scholar]
- 29. He G, Yang Q, Bai L, et al. [Clinical study of preoperative enteral nutrition in elderly colorectal cancer patients with nutritional risk]. Chongqing Yixue [Chongqing Med]. 2017;46:1336-1338. doi: 10.3969/j.issn.1671-8348.2017.10.012 [DOI] [Google Scholar]
- 30. Li D, Fang Y, Su S. [Effect of nursing team-led pre-rehabilitation strategy on patients with colorectal cancer]. Qilu Huli [J Qilu Nurs]. 2021;27:11-13. doi: 10.3969/j.issn.1006-7256.2021.08.004 [DOI] [Google Scholar]
- 31. Loughney L, West MA, Moyses H, et al. The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER trial). Perioper Med. 2021;10:23. doi: 10.1186/s13741-021-00190-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Ma W. [Application and nursing analysis of enteral nutrition in preoperative intestinal preparation for colorectal cancer]. Zhihui Jiankang [Smart Healthcare]. 2020;6:116-117. doi: 10.19335/j.cnki.2096-1219.2020.18.057 [DOI] [Google Scholar]
- 33. Northgraves MJ, Arunachalam L, Madden LA, et al. Feasibility of a novel exercise prehabilitation programme in patients scheduled for elective colorectal surgery: a feasibility randomised controlled trial. Support Care Cancer. 2020;28:3197-3206. doi: 10.1007/s00520-019-05098-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Ommundsen N, Wyller TB, Nesbakken A, et al. Preoperative geriatric assessment and tailored interventions in frail older patients with colorectal cancer: a randomized controlled trial. Colorectal Dis. 2018;20:16-25. doi: 10.1111/codi.13785 [DOI] [PubMed] [Google Scholar]
- 35. Onerup A, Andersson J, Angenete E, et al. Effect of short-term homebased pre- and postoperative exercise on recovery after colorectal cancer surgery (PHYSSURG-C): a randomized clinical trial. Ann Surg. 2022;275:448-455. doi: 10.1097/SLA.0000000000004901 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Peng LH, Wang WJ, Chen J, et al. Implementation of the pre-operative rehabilitation recovery protocol and its effect on the quality of recovery after colorectal surgeries. Chin Med J. 2021;134:2865-2873. doi: 10.1097/CM9.0000000000001709 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Qin P, Jin J, Min S, et al. [Effect of preoperative enhance recovery exercise on postoperative outcome in patients undergoing laparoscopic colorectal cancer surgery]. Yan Maž Wai J Clin Anesthesiol. 2021;37:119-121. doi: 10.12089/jca.2021.02.002 [DOI] [Google Scholar]
- 38. Shen Y, Zhao X, Zhao H, et al. Clinical application of enteral nutrition combined with microbial preparation for intestinal preparation in elderly patients with colorectal cancer. Med Sci Monit. 2022;28:e935366. doi: 10.12659/MSM.935366 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Tian K, Li L, Li X. [Effects of nurse-led cognitive and rehabilitation exercises on postoperative immune function and nutritional status in patients with rectal cancer]. Zhongguo Zhongliu Linchuang Yu Kangfu [Chin J Clin Oncol Rehabil]. 2021;28:509-512. doi: 10.13455/j.cnki.cjcor.2020.04.35 [DOI] [Google Scholar]
- 40. Wang X, Pan W. [Effect of preoperative exercise training based enhanced recovery after surgery on early postoperative rehabilitation of colorectal cancer]. Zhongguo Zhongliu Linchuang Yu Kangfu [Chin J Clin Oncol Rehabil]. 2021;28:1527-1529. doi: 10.13455/j.cnki.cjcor.2021.12.30 [DOI] [Google Scholar]
- 41. Wang X, Gu Y, Chen H, et al. [Effect of preoperative trimodal prehabilitation on rehabilitation of elderly patients with colorectal cancer]. Huli Yanjiu [Chin Nurs Res]. 2022;36:3233-3238. doi: 10.12102/j.issn.1009-6493.2022.18.007 [DOI] [Google Scholar]
- 42. Yan X, Wang Y, Hao D, et al. [Effect of prehabilitation combined with probiotics in elderly laparoscopic colorectal cancer surgery]. Yiyao Qianyan [J Front Med]. 2020;10:160-161. [Google Scholar]
- 43. Yan X. [Effect of preoperative rehabilitation in elderly laparoscopic colorectal cancer surgery]. Zhongguo Laonianxue Zazhi [Chin J Gerontol]. 2021;41:2298-2300. doi: 10.3969/j.issn.1005-9202.2021.11.019 [DOI] [Google Scholar]
- 44. Zhang Y. [Effect of early enteral nutrition support on postoperative nutrition and prognosis of patients with laparoscopic colorectal cancer]. Yiyao Qianyan [J Front Med]. 2019;9:53. [Google Scholar]
- 45. Zhang Q, Zhou H. [Effect of precise nutrition intervention based on acute gastrointestinal injury classification in patients undergoing colorectal cancer surgery]. Zhongxiyi Jiehe Huli [J Clin Nurs Pract]. 2022;8:82-84. [Google Scholar]
- 46. Zhu Y, Liu B. [Effects of enteral nutrition on postoperative status and complications in patients with colorectal cancer]. Jiezhichang Gangmen Waike [J Color Anal Surg]. 2015;21:429-432. [Google Scholar]
- 47. Zhu J. [Application and nursing analysis of enteral nutrition in intestinal preparation before colorectal cancer surgery]. Yixue Shiliao yu Jiankang [Med Diet Heal]. 2022;20:12-15. [Google Scholar]
- 48. Carli F, Bousquet-Dion G, Awasthi R, et al. Effect of Multimodal Prehabilitation vs postoperative rehabilitation on 30-Day postoperative complications for frail patients undergoing resection of colorectal cancer: a randomized clinical trial. JAMA Surg. 2020;155:233-242. doi: 10.1001/jamasurg.2019.5474 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49. Pollentier B, Irons SL, Benedetto CM, et al. Examination of the six minute walk test to determine functional capacity in people with chronic heart failure: a systematic review. Cardiopulm Phys Ther J. 2010;21:13-21. [PMC free article] [PubMed] [Google Scholar]
- 50. Molenaar CJ, van Rooijen SJ, Fokkenrood HJ, et al. Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery. Cochrane Database Syst Rev. 2022;5:CD013259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51. Michael CM, Lehrer EJ, Schmitz KH, Zaorsky NG. Prehabilitation exercise therapy for cancer: a systematic review and meta-analysis. Cancer Med. 2021;10:4195-4205. doi: 10.1002/cam4.4021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. Steinmetz C, Bjarnason-Wehrens B, Walther T, Schaffland TF, Walther C. Efficacy of prehabilitation before cardiac surgery: a systematic review and meta-analysis. Am J Phys Med Rehabil. 2023;102:323-330. doi: 10.1097/PHM.0000000000002097 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53. Daniels SL, Lee MJ, George J, et al. Prehabilitation in elective abdominal cancer surgery in older patients: systematic review and meta-analysis. BJS Open. 2020;4:1022-1041. doi: 10.1002/bjs5.50347 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54. Lau CSM, Chamberlain RS. Prehabilitation programs improve exercise capacity before and after surgery in gastrointestinal cancer surgery patients: a meta-analysis. J Gastrointest Surg. 2020;24:2829-2837. doi: 10.1007/s11605-019-04436-1 [DOI] [PubMed] [Google Scholar]
- 55. Duro-Ocana P, Zambolin F, Jones AW, et al. Efficacy of supervised exercise prehabilitation programs to improve major abdominal surgery outcomes: a systematic review and meta-analysis. J Clin Anesth. 2023;86:111053. doi: 10.1016/j.jclinane.2023.111053 [DOI] [PubMed] [Google Scholar]
- 56. Liu C, Lu Z, Zhu M, Lu X. Trimodal prehabilitation for older surgical patients: a systematic review and meta-analysis. Aging Clin Exp Res. 2022;34:485-494. doi: 10.1007/s40520-021-01929-5 [DOI] [PubMed] [Google Scholar]
- 57. Gillis C, Buhler K, Bresee L, et al. Effects of nutritional prehabilitation, with and without exercise, on outcomes of patients who undergo colorectal surgery: a systematic review and meta-analysis. Gastroenterology. 2018;155:391-410.e4. doi: 10.1053/j.gastro.2018.05.012 [DOI] [PubMed] [Google Scholar]
- 58. Wang D, Wu T, Li Y, et al. A systematic review and meta-analysis of the effect of preoperative exercise intervention on rehabilitation after total knee arthroplasty. Ann Palliat Med. 2021;10:10986-10996. doi: 10.21037/apm-21-2670 [DOI] [PubMed] [Google Scholar]
- 59. Tukanova KH, Chidambaram S, Guidozzi N, et al. Physiotherapy Regimens in esophagectomy and gastrectomy: a systematic review and meta-analysis. Ann Surg Oncol. 2022;29:3148-3167. doi: 10.1245/s10434-021-11122-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60. Arora RC, Brown Ch, 4TH, Sanjanwala RM, McKelvie R. New” prehabilitation: a 3-Way approach to improve postoperative survival and health-related quality of life in cardiac surgery patients. Can J Cardiol. 2018;34:839-849. doi: 10.1016/j.cjca.2018.03.020 [DOI] [PubMed] [Google Scholar]








