Abstract
Purpose
Functional capacity is an independent indicator of morbidity in colon and rectal cancer surgery. This systematic review describes the evaluated and synthesized effects of exercise prehabilitation depending on the duration of interventions on functional and postoperative outcomes in colon and rectal cancer surgery.
Methods
Three electronic databases (MEDLINE Pubmed, Web of Sciences, and Cochrane Registry) were systematically searched (January 2022) for controlled trials that investigated the effects of prehabilitation prior to colo-rectal cancer resection.
Results
Twenty-three studies were included in this systematic review and 14 in our meta-analyses assessing these outcomes: the 6 min walk distance (6MWD), postoperative overall complications, and length of stay (LOS). We observed a significant improvement in preoperative functional capacity as measured with 6MWD (mean difference: 30.8 m; 95% CI 13.3, 48.3; p = 0.0005) due to prehabilitation. No reductions in LOS (mean difference: – 0.27 days; 95% CI – 0.93, 0.40; p = 0.5) or postoperative overall complications (Odds ratio: 0.84; 95% CI 0.53, 1.31; p = 0.44) were observed. Prehabilitation lasting more than 3 weeks tended to lower overall complications (Odds ratio: 0.66; 95% CI 0.4, 1.1; p = 0.11). However, the prehabilitation time periods differed between colon and rectal carcinoma resections.
Conclusion
Prehabilitation while the patient is preparing to undergo surgery for colorectal carcinoma improves functional capacity; and might reduce postoperative overall complications, but does not shorten the LOS. The studies we reviewed differ in target variables, design, and the intervention’s time period. Multicenter studies with sufficient statistical power and differentiating between colon and rectal carcinoma are needed to develop implementation strategies in the health care system.
Registration
PROSPERO CRD42022310532
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Objectives
Colorectal carcinoma (CRC) is one of the most common cancers in Europe and North America (Araghi et al. 2019; Siegel et al. 2020). The only curative approach to treat locally advanced carcinoma is surgical-oncologic resection. However, postoperative complications occur in up to 25% of patients and are associated with higher morbidity and mortality, longer hospital stays, and reduced quality of life (Baum et al. 2019).
Preoperative functional capacity is considered an independent factor in peri- and postoperative complication and morbidity rates (Loewen et al. 2007; Moran et al. 2016b). In addition to the effects of exercise and training in primary and tertiary prevention, physical activity is also practiced more often as prehabilitation before surgery. Prehabilitation includes physical and psychological diagnostics and interventions to improve a patient's current and future health status prior to surgery (Silver and Baima 2013). The main influencing factor on the success of medical exercise prehabilitation is the limited time available before surgery. Nevertheless, the latest Enhanced Recovery After Surgery (ERAS) guidelines include prehabilitation as a preoperative strategy. However, the levels of evidence are generally low to moderate, as are the levels of recommendation (Carmichael et al. 2017; Gustafsson et al. 2019).
The results regarding the functional and postoperative outcomes of prehabilitation in patients undergoing major abdominal cancer surgery are heterogeneous (Daniels et al. 2020; Heger et al. 2020; Hughes et al. 2019; Lambert et al. 2020; Lau and Chamberlain 2020; Waterland et al. 2021). Their comparability is also limited since the preoperative interventions differ in terms of training (methods, intensity, duration, supervision), indications and surgery techniques, presented outcome measures (functional capacity: 6MWT, VO2max; postoperative outcome: complications scores), and quality of study design.
However, there seem to be moderate effects from increasing functional capacity via exercise prehabilitation on improving postoperative outcomes. Several randomized controlled studies have recently been published (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Fulop et al. 2021; Janssen et al. 2019; Karlsson et al. 2019; Moug et al. 2019; Northgraves et al. 2020; Waller et al. 2022). So far, there is no available meta-analysis investigating the influence of the duration of prehabilitation. This systematic review evaluates the evidence of exercise-based prehabilitation’s effects in association with its duration and focusing on patients receiving colorectal cancer surgery. In addition, the aim of this review was to critically analyze the practical realization of care and to develop clinical standards for its realization.
Methods
Search strategy
This review was conducted in accordance with the Cochrane systematic review guidelines and Preferred Reporting Items for Systematic reviews and Meta-Analysis checklist (Moher et al. 2009) and registered with the International Prospective Register of Systematic Reviews (PROSPERO 2022 CRD42022310532). A systematic search of the literature was conducted by four of the authors (RF, CB, JL, IG) in line with the preferred reporting items for systematic reviews guidelines (PRISMA) within the following databases: MEDLINE PubMed, Cochrane Library and Web of Sciences. Applying our search criteria, we identified RCTs and pseudo-randomized controlled trials addressing prehabilitation (including exercise for adults preparing for colorectal cancer surgery between 2009 and 2020) that met our inclusion criteria for meta-analysis (Table 1). Controlled parallel group studies were also screened for this systematic review.
We screened Pubmed (all fields), the Cochrane Library (all fields) and Web of Sciences (all fields) relying on the combinations of search keywords “preoperative exercise abdominal surgery” OR “preoperative exercise colorectal surgery” OR “preoperative exercise colon surgery” OR “preoperative exercise rectal surgery” OR “prehabilitation rectal surgery” OR “prehabilitation colon surgery” OR “prehabilitation abdominal surgery” OR “prehabilitation colorectal surgery”. Our search results were supplemented by a manual search of relevant reviews and their references to ensure that all eligible studies had been included (Fig. 1).
Study selection
Three authors (RF, CB and JL) examined the citations independently and applied pre-agreed selection criteria to identify all potentially eligible studies. Disagreements were resolved through consensus. Papers were considered for inclusion if they were published in English, reported on a prehabilitation or preoperative exercise intervention, and if they reported functional outcomes (6MWD) and/or postoperative outcomes (complications, LOS). Our inclusion criteria are summarized in Table 1.
Data extraction
Study inclusion was initially decided by RF and discussed with senior authors MB and IG. Selected studies were compared in Tables 2 and 3, which include details on sample size, location of cancer surgery (colorectal, colon or rectum), type of prehabilitation intervention, applied exercise intervention (training frequency, session time, intensity), patients’ age, duration of intervention, and main outcomes. Our results are presented using a narrative analysis, primarily grouped according to cancer location, and subsequently by the outcome assessed.
Quality assessment
Each study’s methodological quality was assessed with the Cochrane risk of bias tool (Higgins et al. 2011). Two authors (RF and CB) independently assessed the methodological quality of the selected trials. This tool evaluates the following criteria: method of randomization; allocation concealment; baseline comparability of study groups; and blinding and completeness of follow-up. Trials were graded as having low (green circle), high (red circle), or unclear (yellow circle) risk of bias. Publication bias was evaluated visually with a funnel plot.
Data synthesis and statistical analysis
Data were extracted from the included studies, pooled, and analyzed using random effects models after considering their heterogeneity. For continuous variables, data for meta-analysis were obtained directly from the study results or on request from articles’ authors or calculated from the mean, variance 95% confidence intervals or median and Interquartile range (Higgins et al. 2021; Luo et al. 2018; Shi et al. 2020; Wan et al. 2014). Where the mean and SD of the change from baseline were not presented in the papers, the following equations were used to calculate them:
\({\text{SD}}_{{{\text{change}}}} = \sqrt {{\text{(SD}}_{{{\text{baseline}}}} )^{2} + {\text{(SD}}_{{{\text{endpoint}}}} )^{2} + 2 \times r \times {\text{SD}}_{{{\text{baseline}}}} \times {\text{SD}}_{{{\text{endpoint}}}} }\) (Higgins et al. 2021).
For dichotomous variables, individual and pooled statistics were calculated as odds ratios with 95% CI. RevMan calculator available from Cochrane training were used for pre- and post-interventions assessments (https://training.cochrane.org/resource/revmann-calculator).
A random effects model was used as the trials were clinically heterogeneous and evaluated using the I2 statistic. We classified the results as follows: below 25%, low heterogeneity; between 25 and 75%, possibly moderate heterogeneity; over 75%, considerable heterogeneity.
For all statistical analyses, p < 0.05 was considered statistically significant. Subgroups were defined due to the duration of prehabilitation and analyzed for 6MWD, overall complications and LOS.
Results
In total, we identified 1,341 papers initially during the primary search, of which 428 were duplicates (Fig. 1). Our search was conducted in December 2021. 913 publications were screened for relevance to our review and meta-analysis. Thirty-six articles were identified for full text review; thirteen were excluded (two single arm studies, six re-analyses, four no colorectal surgery, one no functional training) leaving 23 studies for inclusion in systematic review (16 randomized controlled trials and seven cohort studies). Fourteen studies matched our inclusion criteria for meta-analysis (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022) following the exclusion of others (Carli et al. 2010; Chia et al. 2016; Janssen et al. 2019; Li et al. 2013a; Loughney et al. 2017; Minnella et al. 2020; Mora López et al. 2020; van Rooijen et al. 2019; West et al. 2015) (7 cohort studies, 2 no standard care control group). In these 14 studies, 1,648 patients were involved in an intervention or control group (including dropouts). Postoperative complications were the most commonly reported clinical outcomes, and the 6-min walk test (6MWT) was the main functional assessment used. Table 2 summarizes the characteristics and main outcomes of studies included in our qualitative synthesis (studies included in the meta-analysis are marked).
Study characteristics for meta-analysis and outcome measures
Thirteen of the trials evaluated prehabilitation in patients preparing to undergo colorectal resection (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022) and one trial in patients undergoing rectal surgery only (Moug et al. 2019). These studies evaluated a total number of 1,461 patients (without dropouts), of whom 719 participated in a preoperative exercise intervention. Although the training protocols differed widely, endurance training was always included. The remaining 742 patients not undergoing prehabilitation training served as controls. The control group received standard care in 12 trials (Barberan-Garcia et al. 2018; Berkel et al. 2022; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022). Two studies provided the control group patients n home-based or general exercise advice (Bousquet-Dion et al. 2018; Dronkers et al. 2010).
Primary outcomes varied across studies, focusing on the improvement of functional capacity measured in most studies via the 6MWT (Barberan-Garcia et al. 2018; Bousquet-Dion et al. 2018; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022) and in three studies via oxygen uptake during incremental exercise testing (Berkel et al. 2022; Dronkers et al. 2010; Kim et al. 2009). The primary postoperative outcomes were assessed according to numbers of postoperative complications or by Comprehensive Complications Index (CCI) (Berkel et al. 2022; Carli et al. 2020; Onerup et al. 2021). The severity of complications were determined by relying on the Clavien–Dindo rating in the majority of studies (Barberan-Garcia et al. 2018; Berkel et al. 2022; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; López-Rodríguez-Arias et al. 2021; Onerup et al. 2021), whereby only four studies reported complete results (Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Onerup et al. 2021). Only five studies reported comprehensively the types of complications (Barberan-Garcia et al. 2018; Berkel et al. 2022; Carli et al. 2020; Gillis et al. 2014; Onerup et al. 2021). The surgical procedure used has been reported in ten studies (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021). No study used only open or laparoscopic procedures. In the majority of studies, the proportion of laparoscopic procedures was over 50% (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Onerup et al. 2021) and ranged from 17 to 97%. Only two studies reported a proportion of open surgeries above 50% (Moug et al. 2019; Northgraves et al. 2020). In ten publications, information on neoadjuvant therapy was described or neoadjuvant therapy was given as an exclusion criterion (Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021). 338 included patients (intervention group: 165; control group 173) received neoadjuvant therapy. Detailed information on comorbidities (e.g. diabetes mellitus, cardiovascular diseases, pulmonary diseases and smoking) could be found in nine publications (Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Onerup et al. 2021). No study described a possible influence of comorbidity on outcome parameters.
Exercise interventions
Exercise interventions were described according to their intensity, frequency, and type of exercise in varying detail. Ten studies described the exercise intervention comprehensively (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Dronkers et al. 2010; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022). The majority of studies included multimodal exercise interventions including aerobic, resistance (Berkel et al. 2022; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Li et al. 2013a; López-Rodríguez-Arias et al. 2021; Waller et al. 2022) and inspiratory muscle training (Dronkers et al. 2010; Karlsson et al. 2019). An ergometer or stepper was used as load exercise equipment in some studies (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020). Table 3 summarizes the exercise interventions in all studies. The intensity of exercise was determined and adapted in the intervention period by applying perceived exertion (RPE), percentage of maximum heart rate, daily steps count or percent of maximum work rate. One of the studies failed to provide sufficient data on intervention monitoring (López-Rodríguez-Arias et al. 2021).
Control groups
Patients undergoing prehabilitation were compared to control groups that nearly all entailed standard care involving no preoperative exercise. The control group was given exercise advice only in the studies by Bousquet-Dion et al. 2018, Carli et al. 2010 and Dronkers et al. 2010. Three trials applied the same exercise interventions in the control group during the postoperative rather than the preoperative period (waiting control-group design) (Bousquet-Dion et al. 2018; Carli et al. 2020; Gillis et al. 2014). In six studies, only recommendations were made to control-group patients, i.e., advice on smoking cessation, on psychological or physical activity, or ERAS-guidelines were followed (Barberan-Garcia et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Kim et al. 2009; Northgraves et al. 2020).
Main outcome parameter
Ten studies measured functional capacity (Fig. 2) via the 6MWD (Barberan-Garcia et al. 2018; Bousquet-Dion et al. 2018; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; Moug et al. 2019; Northgraves et al. 2020; Waller et al. 2022), but not all reported data in comparable indices that would have justified inclusion in our meta-analysis (Barberan-Garcia et al. 2018; Fulop et al. 2021; Karlsson et al. 2019; Moug et al. 2019; Waller et al. 2022). We, therefore, had to calculate mean differences and standard deviations from median, confidence intervals or interquartile ranges regarding certain 6MWD results (Higgins et al. 2021; Luo et al. 2018; Shi et al. 2020; Wan et al. 2014). Our analysis of change in walking distance after prehabilitation demonstrated a significant improvement in functional capacity at a moderate evidence level (MD 31 m; 95% CI 13.3, 48.3; p = 0.0005; I2 = 68%; Fig. 2). Our subgroup analysis showed no differences. Two of the studies we could not include in meta-analysis (no randomized parallel group trials) reported a significant increase in the walking distance or oxygen consumption (Li et al. 2013a; West et al. 2015), while the remaining study reported no improvement in exercise capacity through the preoperative exercise intervention (Minnella et al. 2020). Some studies reported a change in physical activity or daily steps before and after prehabilitation (Barberan-Garcia et al. 2018; Loughney et al. 2016; Moug et al. 2019).
Overall postoperative complications (Fig. 3) were reported in 11 studies (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Onerup et al. 2021). Meta-analysis delivered no significant results (OR 0.84; 95% CI 0.53–1.31; p = 0.44; I2 = 62%; Fig. 3). However, we noted a trend towards a non-significant reduction in the prehabilitation subgroup in conjunction with a duration > 3 weeks (OR 0.66; 95% CI 0.4–1.1; p = 0.11; I2 = 52%; Fig. 3). Trials involving prehabilitation lasting less than 3 weeks showed no effect on postoperative complications (OR 1.44; 95% CI 0.78–2.67; p = 0.261; I2 = 25%; Fig. 2). The test of differences in postoperative complications between subgroups of more or less than 3 weeks’ duration of prehabilitation was significant (p = 0.05; I2 = 72.9%; Fig. 3).
12 Studies reporting on length of hospital stay (LOS) (Fig. 4) could be included in our meta-analysis (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021), which demonstrated no evidence showing that prehabilitation reduces this parameter (MD – 0.26 days; 95% CI – 0.89, 0.37; p = 0.42; I2 = 31%; Fig. 4). There were no differences in and between subgroups (Fig. 4).
Eighteen studies (meta-analysis and systematic review) reported on dropouts (Table 2) in their intervention and control group during the intervention period (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2010, 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; Li et al. 2013a; López-Rodríguez-Arias et al. 2021; Loughney et al. 2016; Moug et al. 2019; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022; West et al. 2015). The prehabilitation was abandoned by 14% of intervention-group patients for various reasons. The adherence to exercise interventions (Table 3) varied from 68 to 98% in the included trials (Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; Northgraves et al. 2020; Waller et al. 2022). Adverse or serious adverse events (Table 3) were rare during the trials (Barberan-Garcia et al. 2018; Berkel et al. 2022; Carli et al. 2020; Karlsson et al. 2019; Kim et al. 2009; Moug et al. 2019; Onerup et al. 2021; Waller et al. 2022). Only five events, such as pain, dizziness or malaise were described (Karlsson et al. 2019; Kim et al. 2009; Onerup et al. 2021), and no major side-effects occurred.
The duration (Table 3) of prehabilitation varied between 2 and 14 weeks. The majority of included studies did not differentiate between colon and rectal carcinomas in prehabilitation terms (Barberan-Garcia et al. 2018; Bousquet-Dion et al. 2018; Carli et al. 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Northgraves et al. 2020; Waller et al. 2022). In these trials, the mean prehabilitation lasted 4 weeks. The prehabilitation period was significantly longer (11.7 weeks) only in patients preparing for rectal cancer surgery (Berkel et al. 2022; Brunet et al. 2021; Heldens et al. 2016; Loughney et al. 2016; Moug et al. 2019; Singh et al. 2018; West et al. 2015). This was associated with respective neoadjuvant radiochemotherapy.
Risk of bias and quality of evidence
Five studies were assessed as having a low risk of bias (Berkel et al. 2022; Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Onerup et al. 2021). None showed a high risk of bias, and in nine trials we had concerns about the risk of bias due to insufficient recruitment (in relation to sample size calculation) or too few details on methodology (randomization, concealment of randomization, blinding), high dropout rates, and inappropriate measures (Barberan-Garcia et al. 2018; Bousquet-Dion et al. 2018; Dronkers et al. 2010; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Moug et al. 2019; Northgraves et al. 2020; Waller et al. 2022) (Fig. 5). Figure 6 shows the funnel plots for the analyzed trials.
Discussion
Our review and meta-analysis include randomized controlled intervention trials and cohort studies, which involved exercise-based prehabilitation in patients preparing for colorectal surgical resection. In contrast to previous meta-analyses (Daniels et al. 2020; Hughes et al. 2019; Waterland et al. 2021), our main focus shifted to colon and rectal resection rather than abdominal surgery (Berkel et al. 2022; Carli et al. 2020; Fulop et al. 2021; López-Rodríguez-Arias et al. 2021; Northgraves et al. 2020; Onerup et al. 2021; Waller et al. 2022, 2022); second, the duration of preoperative exercise intervention; and third, new studies published since the last meta-analysis were included (Berkel et al. 2022; Fulop et al. 2021; López-Rodríguez-Arias et al. 2021; Onerup et al. 2021; Waller et al. 2022).
Together with the latest literature, our review provides clear evidence for an increase in functional capacity through prehabilitation as measured by 6MWT (Lau and Chamberlain 2020; Waterland et al. 2021). Postoperative outcomes revealed indifferent results showing seemingly declining overall complications in association with prehabilitation periods lasting more than 3 weeks, but no reduction in length of hospital stay. Despite these findings, the interest in prehabilitaton prior to colorectal surgery has been growing, but not clinically adopted to improve peri- and postoperative outcomes following colorectal cancer surgery. We also found that as preoperative periods for colon and rectal cancers vary in their duration between diagnosis and surgery due to the neoadjuvant radiochemotherapy prior rectal carcinoma resection, exercise-based interventions should be planned differently (4 vs. 12 weeks; Table 3). Only few studies differentiated between colon and rectal carcinoma surgery (Berkel et al. 2022; Moug et al. 2019).
Numerous peri- and postoperative procedures, known as Enhanced Recovery After Surgery (ERAS) programs, have demonstrated significant benefits, reducing LOS, total complications, and hospital costs across many different surgical procedures (Lau and Chamberlain 2017). Because of brief time intervals before surgery, these programs seldom include preoperative exercise interventions (Bruns et al. 2016). This data synthesis demonstrated, as had previous meta-analyses (Hughes et al. 2019; Lambert et al. 2020; Lau and Chamberlain 2020; Waterland et al. 2021), an increase in functional capacity after colorectal surgery. Our review and analysis findings have limited applicability for several reasons, namely small samples in some of the included trials, the varied durations of some exercise interventions, variations in exercise intensity and in exercise methods, and the wide range of reported outcomes (differences in measurements and statistical parameters). The adherence to an exercise intervention ranged from 68 to 98% in the included studies (Bousquet-Dion et al. 2018; Carli et al. 2020).
Functional capacity
There is evidence that patients with low physical capacity have higher peri- and postoperative morbidity and mortality (Heldens et al. 2017; Snowden et al. 2013) and develop more postoperative cardiopulmonary complications (Lee et al. 2013). As a "controlled trauma", surgery induces a strong stress response and reduces functional capacity that can vary largely between individuals (Prete et al. 2018). Therefore, the goals of preoperative conditioning via physical exercise are to increase physical functional capacity to maintain or enhance quality of life, regenerative capacity, and to improve postoperative outcomes.
Our meta-analysis demonstrates a statistically significant increase of 31 6MWD meters (95% CI: 13–45 m; Fig. 2) regardless of prehabilitation’s duration after uni- and multimodal prehabilitation via an exercise intervention. This amounts to a relative change of approximately of 15%, and is in accordance with previous meta-analyses involving abdominal surgery (Daniels et al. 2020; Waterland et al. 2021).
A patient’s preoperative 6MWD is associated with the incidence of postoperative complications (Hayashi et al. 2017) and a valid, reliable parameter with which to determine exercise capacity in cancer patients (Moriello et al. 2008; Schmidt et al. 2013). An absolute change of 22–42 m in 6MWD is clinically relevant in lung cancer patients and correlated with a better function, physical activity and dyspnea (Granger et al. 2015). There is evidence of a strong positive correlation between weekly caloric expenditure (Courneya et al. 2016) and cardio-respiratory fitness (Schmid and Leitzmann 2015) and mortality prognosis in tumor patients. In contrast, Hughes et al. (2019) reported no preoperative 6MWD enhancement with three included studies. There are large differences in the time from CRC diagnosis to surgery depending on the tumor location. Patients suffering from colon cancer usually undergo tumor resection within few days to a maximum of three to four weeks (Berkel et al. 2022; Bojesen et al. 2022; Li et al. 2013b). In contrast, patients with rectal cancer receive neoadjuvant radiochemotherapy, i.e., gaining approximately 3 months from initial diagnosis to surgery (Berkel et al. 2022; Brunet et al. 2021; Heldens et al. 2016; Loughney et al. 2016; Singh et al. 2018; West et al. 2015). This period enables a significant increase in functional capacity via physiological adaptations of the cardiovascular system and musculature through a planned exercise-medical training intervention (Moug et al. 2019; West et al. 2015). Accordingly, exercise-medical prehabilitation in preparation for surgery should pursue different goals depending on the carcinoma and be structured accordingly.
Training to improve physical performance and cardiopulmonary capacity must be planned, structured, individually dosed, progressive, and done regularly to trigger physiological adaptations (Medicine 2013; Tew et al. 2018). Considering that cardiovascular function is an independent indicator of mortality and length of hospital stay, from the conditioning point of view, cardiopulmonary function is an especially important aspect of physical performance in all prevention and therapy periods (Older and Hall 2004; Snowden et al. 2013). The prehabilitation intervention should thus focus on endurance or strength endurance-based training (Barberan-Garcia et al. 2018; Berkel et al. 2022; Bousquet-Dion et al. 2018; Carli et al. 2010, 2020; Dronkers et al. 2010; Fulop et al. 2021; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; López-Rodríguez-Arias et al. 2021; Northgraves et al. 2020; Waller et al. 2022).
In conclusion, because of the brief interval before surgery lasting just days or weeks, only a small increase in physical performance and functional capacity is likely through prehabilitation (Bruns et al. 2016; Lau and Chamberlain 2020). Overall, however, although the evidence of an increase in physical capacity by briefly engaging in preoperative training is inconclusive, we can assume that the 6MWD increases (Daniels et al. 2020; Gillis et al. 2018; Heger et al. 2020; Lau and Chamberlain 2020; Waterland et al. 2021). The three reasons for the limited enhancement of functional performance are the very heterogeneous prehabilitation measures of varying duration and differing baseline functional performance levels of patients. All these factors make it difficult to develop individual and therapeutically beneficial exercise programs for these patients. However, severely performance-impaired patients with CRC seem to benefit from a performance-enhancing effect from preoperative training programs lasting at least 3 weeks (Minnella et al. 2020).
Postoperative outcomes
There are reports of approximately 2-day reductions in LOS specifically for CRC (Gillis et al. 2018) and generally for abdominal surgery (Lambert et al. 2020; Waterland et al. 2021). In contrast, our meta-analysis failed to show any significant reduction in postoperative outcomes (overall complications and LOS; Fig. 3 and 4). Overall, we observed no change in the incidence of postoperative complications in prehabilitated patients, but we did detect an effect dependent on the duration of prehabilitation (Fig. 3). Preoperative exercise helping to enhance the physical reconditioning of patients undergoing surgery is likely to improve postoperative outcomes. A differentiated analysis of postoperative complications according to severity or surgery-related vs. non-surgery-related could not be performed due an insufficient amount of data. For a data analysis of the severity, only four studies could have been used (Carli et al. 2020; Fulop et al. 2021; Gillis et al. 2014; Onerup et al. 2021). Only five studies reported comprehensively the types of complications (Barberan-Garcia et al. 2018; Berkel et al. 2022; Carli et al. 2020; Gillis et al. 2014; Onerup et al. 2021), whereby four studies separated into surgical and non-surgical complications (Barberan-Garcia et al. 2018; Berkel et al. 2022; Carli et al. 2020; López-Rodríguez-Arias et al. 2021).
From a physiological point of view, it seems necessary that enhanced functional capacity including cardiopulmonary fitness is associated with a more rapid postoperative recovery and depends on the intervention’s duration in inducing exercise-based adaptations. The strong relations between preoperative cardiopulmonary fitness and postoperative complications are evidence thereof (Heldens et al. 2017; Lee et al. 2013; Moran et al. 2016b; Snowden et al. 2013; Steffens et al. 2019). So, the main aim of prehabilitation should be to improve the patient’s physical performance and initiate regenerative tissue processes. The key factor in prehabilitation’s enhancement effect is, therefore, the presurgical efficacy of training, that is, adequate intensity and an exercise intervention lasting long enough. As our organ system’s training-induced adaptations occur at varying intervals (Lundby et al. 2017), differences in our subgroup analysis depending on prehabilitation’s duration are plausible.
In summary, the evidence of an increase in physical capacity via short preoperative training interventions is only moderate (Daniels et al. 2020; Gillis et al. 2018; Heger et al. 2020; Lau and Chamberlain 2020; Waterland et al. 2021). Nevertheless, adequate duration of prehabilitation could enable the beneficial physiological adaptations in functional capacity such as those that rectal carcinoma patients achieve (having up to 3 months to exercise before their surgical resection). A prolonged time period prior to colorectal surgery does not result in shortening CRC patients’ overall or cancer-free survival after surgical therapy (Curtis et al. 2018; Strous et al. 2019). Engaging in exercise prehabilitation before oncologic surgery is feasible, but research findings on postoperative complication rates after abdominal surgery have been inconsistent (Barberan-Garcia et al. 2018; Gillis et al. 2018; Heger et al. 2020; Hughes et al. 2019; Lambert et al. 2020; Lau and Chamberlain 2020; Moran et al. 2016a). Despite this non-significant effect of reducing the length of hospital stay, but rather of reducing postoperative complications in colorectal surgery, we believe that prehabilitation may be effective in patients undergoing other types of oncologic visceral surgery (Gillis et al. 2018; Lambert et al. 2020; Waterland et al. 2021).
The latest ERAS guidelines recommend prehabilitation as a preoperative strategy (Gustafsson et al. 2019). Despite the protective, therapeutic, and regenerative efficiency of physical training, a systematic implementation strategy is still lacking. Although physical training also results in significant improvement in several comorbidities, this effective therapy option is currently not used to its full potential. Postoperative complications are extremely costly in intensive care medicine (Vonlanthen et al. 2011). The theoretical reduction in postoperative complications we suspect, and the shortening of hospital stays that a prehabilitation intervention might trigger, could thus potentially lower the overall health care and treatment costs for colorectal surgery. In terms of feasibility, preoperative training interventions are known to be as safe, applicable, and associated with high adherence (Loughney et al. 2016).
Adherence and Compliance
The studies we reviewed showed strong adherence to training interventions (Berkel et al. 2022; Bousquet-Dion et al. 2018; Dronkers et al. 2010; Gillis et al. 2014; Karlsson et al. 2019; Kim et al. 2009; Northgraves et al. 2020; Waller et al. 2022).. Essential factors for strong patient adherence in exercise therapy are continuous supervision, the consideration of each patient’s physical condition when planning exercises (e.g. overweight, joint problems, shoulder pain after breast surgery) and regular communication with the care team. Objective performance measurements to assess physical resilience should be incorporated in the process. Online-based and health applications in this area are currently being developed and evaluated (Falz et al. 2021). In exercise medicine therapy for cancer, the current American College of Sports Medicine (ACSM) recommendation should generally be considered as a lower limit (Rock et al. 2012). Since these volumes are rarely achievable during chemotherapy or radiotherapy, and generally in pre- or postoperatively weak patients, the training activities must be individually adapted. For this purpose, the intensity, type of stress or postoperative condition, training frequency and duration must be individually diagnosed and individualized during the therapy course.
Limitations
This systematic review has several limitations, above all the inhomogeneous studies themselves. Most of them enrolled low numbers of participants undergoing colorectal surgery only. However, the time from diagnosis to surgery differed considerably depending on whether the patients had colon or rectal cancer. The trials we included tended to be very heterogeneous in their intervention duration, exercise regimens, and patient ages. An implementation structure for exercise medicine therapy approaches has not yet been established in the health care system, constituting a major hindrance for making recommendations on conditioning concepts in colorectal tumor surgery. We observed diverse variables and parameters in studies with similar designs, objectives, and interventions. Many studies failed to thoroughly describe the training intervention (i.e., its duration and intensity) – information that is necessary to accurately assess performance-enhancing adaptations. Further subgroup analyses e.g. with regard to the surgical procedure (laparoscopic vs. open surgery) or type of exercise (aerobic vs. resistance training; supervised vs. non-supervised) could not performed due to missing discrimination of the patient groups or insufficient available data.
Conclusion
Based on the available evidence from RCTs and cohort studies, this review demonstrated that individual preoperative exercise interventions in patients undergoing colorectal cancer surgery improved functional exercise capacity. We also detected a tendency toward fewer postoperative complications when the exercise prehabilitation lasted at least 3 weeks, preferably longer. We identified no shortening of hospital stays attributable to prehabilitation. Our results should be interpreted cautiously because of the heterogeneity of available studies. Future trials involving multiple centers, with larger cohorts, and differentiated according to the cancer location in the colon or rectum as well as the extent of colorectal surgery (laparoscopic vs. open), are needed. The information reported should include the training intervention’s total length (in hours) and exertional intensity (percent of maximum power or maximum heart rate) to determine dose–response relationships and make evidence-based recommendations.
Data availability
The original contributions presented in the study are included in the article supplementary material; further inquiries can be directed to the corresponding author/s.
References
Araghi M, Soerjomataram I, Jenkins M, Brierley J, Morris E, Bray F, Arnold M (2019) Global trends in colorectal cancer mortality: projections to the year 2035. Int J Cancer 144:2992–3000
Barberan-Garcia A, Ubré M, Roca J, Lacy AM, Burgos F, Risco R, Momblán D, Balust J, Blanco I, Martínez-Pallí G (2018) Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery: a randomized blinded controlled trial. Ann Surg 267:50–56
Baum P, Diers J, Lichthardt S, Kastner C, Schlegel N, Germer C-T, Wiegering A (2019) Mortality and complications following visceral surgery: a nationwide analysis based on the diagnostic categories used in German hospital invoicing data. Dtsch Arztebl Int 116:739–746
Berkel AEM, Bongers BC, Kotte H, Weltevreden P, de Jongh FHC, Eijsvogel MMM, Wymenga M, Bigirwamungu-Bargeman M, van der Palen J, van Det MJ, van Meeteren NLU, Klaase JM (2022) 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 275:e299–e306
Bojesen RD, Jørgensen LB, Grube C, Skou ST, Johansen C, Dalton SO, Gögenur I (2022) Fit for Surgery-feasibility of short-course multimodal individualized prehabilitation in high-risk frail colon cancer patients prior to surgery. Pilot Feasibility Stud 8:11
Bousquet-Dion G, Awasthi R, Loiselle S-È, Minnella EM, Agnihotram RV, Bergdahl A, Carli F, Scheede-Bergdahl C (2018) Evaluation of supervised multimodal prehabilitation programme in cancer patients undergoing colorectal resection: a randomized control trial. Acta Oncol 57:849–859
Brunet J, Price J, Delluc C (2021) An exercise trial for adults undergoing neoadjuvant chemoradiotherapy for rectal cancer proves not feasible: recommendations for future trials. Trials 22:26
Bruns ERJ, van den Heuvel B, Buskens CJ, van Duijvendijk P, Festen S, Wassenaar EB, van der Zaag ES, Bemelman WA, van Munster BC (2016) The effects of physical prehabilitation in elderly patients undergoing colorectal surgery: a systematic review. Colorectal Dis 18:O267-277
Carli F, Charlebois P, Stein B, Feldman L, Zavorsky G, Kim DJ, Scott S, Mayo NE (2010) Randomized clinical trial of prehabilitation in colorectal surgery. Br J Surg 97:1187–1197
Carli F, Bousquet-Dion G, Awasthi R, Elsherbini N, Liberman S, Boutros M, Stein B, Charlebois P, Ghitulescu G, Morin N, Jagoe T, Scheede-Bergdahl C, Minnella EM, Fiore JF (2020) 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 155:233–242
Carmichael JC, Keller DS, Baldini G, Bordeianou L, Weiss E, Lee L, Boutros M, McClane J, Feldman LS, Steele SR (2017) Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American society of colon and rectal surgeons and society of American gastrointestinal and endoscopic surgeons. Dis Colon Rectum 60:761–784
Chia CLK, Mantoo SK, Tan KY (2016) “Start to finish trans-institutional transdisciplinary care”: a novel approach improves colorectal surgical results in frail elderly patients. Colorectal Dis 18:O43-50
Courneya KS, Vardy JL, O’Callaghan CJ, Friedenreich CM, Campbell KL, Prapavessis H, Crawford JJ, O’Brien P, Dhillon HM, Jonker DJ, Chua NS, Lupichuk S, Sanatani MS, Gill S, Meyer RM, Begbie S, Bonaventura T, Burge ME, Turner J, Tu D, Booth CM (2016) Effects of a structured exercise program on physical activity and fitness in colon cancer survivors: one year feasibility results from the CHALLENGE trial. Cancer Epidemiol Biomarkers Prev 25:969–977
Curtis NJ, West MA, Salib E, Ockrim J, Allison AS, Dalton R, Francis NK (2018) Time from colorectal cancer diagnosis to laparoscopic curative surgery-is there a safe window for prehabilitation? Int J Colorectal Dis 33:979–983
Daniels SL, Lee MJ, George J, Kerr K, Moug S, Wilson TR, Brown SR, Wyld L (2020) Prehabilitation in elective abdominal cancer surgery in older patients: systematic review and meta-analysis. BJS Open. https://doi.org/10.1002/bjs5.50347
Dronkers JJ, Lamberts H, Reutelingsperger IMMD, Naber RH, Dronkers-Landman CM, Veldman A, van Meeteren NLU (2010) Preoperative therapeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study. Clin Rehabil 24:614–622
Falz R, Thieme R, Tegtbur U, Bischoff C, Leps C, Hillemanns P, Kohlhaw K, Klempnauer J, Lordick F, Stolzenburg J-U, Aktas B, Weitz J, Bork U, Wimberger P, Thomas C, Biemann R, Jansen-Winkeln B, Schulze A, Gockel I, Busse M (2021) CRBP-TS - evaluation of a home-based training and health care program for colorectal, breast, and prostate cancer using telemonitoring and self-management: study protocol for a randomized controlled trial. BMC Sports Sci Med Rehabil 13:15
Fulop A, Lakatos L, Susztak N, Szijarto A, Banky B (2021) The effect of trimodal prehabilitation on the physical and psychological health of patients undergoing colorectal surgery: a randomised clinical trial. Anaesthesia 76:82–90
Gillis C, Li C, Lee L, Awasthi R, Augustin B, Gamsa A, Liberman AS, Stein B, Charlebois P, Feldman LS, Carli F (2014) Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer. Anesthesiology 121:937–947
Gillis C, Buhler K, Bresee L, Carli F, Gramlich L, Culos-Reed N, Sajobi TT, Fenton TR (2018) Effects of nutritional prehabilitation, with and without exercise, on outcomes of patients who undergo colorectal surgery: a systematic review and meta-analysis. Gastroenterology 155:391-410.e4
Granger CL, Holland AE, Gordon IR, Denehy L (2015) Minimal important difference of the 6-minute walk distance in lung cancer. Chron Respir Dis 12:146–154
Gustafsson UO, Scott MJ, Hubner M, Nygren J, Demartines N, Francis N, Rockall TA, Young-Fadok TM, Hill AG, Soop M, de Boer HD, Urman RD, Chang GJ, Fichera A, Kessler H, Grass F, Whang EE, Fawcett WJ, Carli F, Lobo DN, Rollins KE, Balfour A, Baldini G, Riedel B, Ljungqvist O (2019) Guidelines for perioperative care in elective colorectal surgery: Enhanced Recovery After Surgery (ERAS®) society recommendations: 2018. World J Surg 43:659–695
Hayashi K, Yokoyama Y, Nakajima H, Nagino M, Inoue T, Nagaya M, Hattori K, Kadono I, Ito S, Nishida Y (2017) Preoperative 6-minute walk distance accurately predicts postoperative complications after operations for hepato-pancreato-biliary cancer. Surgery 161:525–532
Heger P, Probst P, Wiskemann J, Steindorf K, Diener MK, Mihaljevic AL (2020) A systematic review and meta-analysis of physical exercise prehabilitation in major abdominal surgery (PROSPERO 2017 CRD42017080366). J Gastrointest Surg 24:1375–1385
Heldens AFJM, Bongers BC, de Vos-Geelen J, van Meeteren NLU, Lenssen AF (2016) Feasibility and preliminary effectiveness of a physical exercise training program during neoadjuvant chemoradiotherapy in individual patients with rectal cancer prior to major elective surgery. Eur J Surg Oncol 42:1322–1330
Heldens AFJM, Bongers BC, Lenssen AF, Stassen LPS, Buhre WF, van Meeteren NLU (2017) The association between performance parameters of physical fitness and postoperative outcomes in patients undergoing colorectal surgery: an evaluation of care data. Eur J Surg Oncol 43:2084–2092
Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JAC, Cochrane Bias Methods Group, Cochrane Statistical Methods Group (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928
Higgins J, Thomas J, Chandler J, Cumpston M, Page M, Welch V (2021) Cochrane handbook for systematic reviews of interventions. Version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook
Hughes MJ, Hackney RJ, Lamb PJ, Wigmore SJ, Christopher Deans DA, Skipworth RJE (2019) Prehabilitation before major abdominal surgery: a systematic review and meta-analysis. World J Surg 43:1661–1668
Janssen TL, Steyerberg EW, Langenberg JCM, de Lepper CVH, Wielders D, Seerden TCJ, de Lange DC, Wijsman JH, Ho GH, Gobardhan PD, van Alphen R, van der Laan L (2019) Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: an uncontrolled before-and-after study. PLoS One 14:e0218152
Karlsson E, Farahnak P, Franzén E, Nygren-Bonnier M, Dronkers J, van Meeteren N, Rydwik E (2019) Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery - a randomized controlled design. PLoS ONE 14:e0219158
Kim DJ, Mayo NE, Carli F, Montgomery DL, Zavorsky GS (2009) Responsive measures to prehabilitation in patients undergoing bowel resection surgery. Tohoku J Exp Med 217:109–115
Lambert J, Hayes L, Keegan T, Subar D, Gaffney C (2020) The impact of prehabilitation on patient outcomes in hepatobiliary, colorectal, and upper gastrointestinal cancer surgery: a PRISMA-accordant meta-analysis. Ann Surg. https://doi.org/10.1097/SLA.0000000000004527
Lau CSM, Chamberlain RS (2017) Enhanced Recovery After Surgery programs improve patient outcomes and recovery: a meta-analysis. World J Surg 41:899–913
Lau CSM, Chamberlain RS (2020) Prehabilitation programs improve exercise capacity before and after surgery in gastrointestinal cancer surgery patients: a meta-analysis. J Gastrointest Surg 24:2829–2837
Lee L, Schwartzman K, Carli F, Zavorsky GS, Li C, Charlebois P, Stein B, Liberman AS, Fried GM, Feldman LS (2013) The association of the distance walked in 6 min with pre-operative peak oxygen consumption and complications 1 month after colorectal resection. Anaesthesia 68:811–816
Li C, Carli F, Lee L, Charlebois P, Stein B, Liberman AS, Kaneva P, Augustin B, Wongyingsinn M, Gamsa A, Kim DJ, Vassiliou MC, Feldman LS (2013a) Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study. Surg Endosc 27:1072–1082
Li X, Scarfe A, King K, Fenton D, Butts C, Winget M (2013b) Timeliness of cancer care from diagnosis to treatment: a comparison between patients with breast, colon, rectal or lung cancer. Int J Qual Health Care 25:197–204
Loewen GM, Watson D, Kohman L, Herndon JE, Shennib H, Kernstine K, Olak J, Mador MJ, Harpole D, Sugarbaker D, Green M (2007) Preoperative exercise Vo2 measurement for lung resection candidates: results of cancer and leukemia group B protocol 9238. J Thorac Oncol 2:619–625
López-Rodríguez-Arias F, Sánchez-Guillén L, Aranaz-Ostáriz V, Triguero-Cánovas D, Lario-Pérez S, Barber-Valles X, Lacueva FJ, Ramirez JM, Arroyo A (2021) Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic. Support Care Cancer 29:7785–7791
Loughney L, West MA, Kemp GJ, Grocott MPW, Jack S (2016) Exercise intervention in people with cancer undergoing neoadjuvant cancer treatment and surgery: a systematic review. Eur J Surg Oncol 42:28–38
Loughney L, West MA, Dimitrov BD, Kemp GJ, Grocott MP, Jack S (2017) Physical activity levels in locally advanced rectal cancer patients following neoadjuvant chemoradiotherapy and an exercise training programme before surgery: a pilot study. Perioper Med (Lond) 6:3
Lundby C, Montero D, Joyner M (2017) Biology of VO2 max: looking under the physiology lamp. Acta Physiol (oxf) 220:218–228
Luo D, Wan X, Liu J, Tong T (2018) Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 27:1785–1805
Medicine AC of S (2013) ACSM’s Guidelines for Exercise Testing and Prescription. Lippincott Williams & Wilkins.
Minnella EM, Ferreira V, Awasthi R, Charlebois P, Stein B, Liberman AS, Scheede-Bergdahl C, Morais JA, Carli F (2020) Effect of two different pre-operative exercise training regimens before colorectal surgery on functional capacity: a randomised controlled trial. Eur J Anaesthesiol 37:969–978
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097
Mora López L, Pallisera Llovera A, Serra-Aracil X, Serra Pla S, Lucas Guerrero V, Rebasa P, Tremps Domínguez C, Pujol Caballé G, Martínez Castela R, Subirana Giménez L, Martínez Cabañero J, Del Pino ZC, Agudo Arcos C, Carol Boeris FG, Navarro SS (2020) A single-center prospective observational study on the effect of trimodal prehabilitation in colorectal surgery. Cir Esp (engl Ed) 98:605–611
Moran J, Guinan E, McCormick P, Larkin J, Mockler D, Hussey J, Moriarty J, Wilson F (2016a) The ability of prehabilitation to influence postoperative outcome after intra-abdominal operation: a systematic review and meta-analysis. Surgery 160:1189–1201
Moran J, Wilson F, Guinan E, McCormick P, Hussey J, Moriarty J (2016b) Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review. Br J Anaesth 116:177–191
Moriello C, Mayo NE, Feldman L, Carli F (2008) Validating the six-minute walk test as a measure of recovery after elective colon resection surgery. Arch Phys Med Rehabil 89:1083–1089
Moug SJ, Mutrie N, Barry SJE, Mackay G, Steele RJC, Boachie C, Buchan C, Anderson AS (2019) Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration: results from the REx trial. Colorectal Dis 21:548–562
Northgraves MJ, Arunachalam L, Madden LA, Marshall P, Hartley JE, MacFie J, Vince RV (2020) Feasibility of a novel exercise prehabilitation programme in patients scheduled for elective colorectal surgery: a feasibility randomised controlled trial. Support Care Cancer 28:3197–3206
Older P, Hall A (2004) Clinical review: how to identify high-risk surgical patients. Crit Care 8:369–372
Onerup A, Andersson J, Angenete E, Bock D, Börjesson M, Ehrencrona C, Olsén MF, Larsson P-A, de la Croix H, Wedin A, Haglind E (2021) Effect of short-term homebased pre- and postoperative exercise on recovery after colorectal cancer surgery (PHYSSURG-C): a randomized clinical trial. Ann Surg. https://doi.org/10.1097/SLA.0000000000004901
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71
Prete A, Yan Q, Al-Tarrah K, Akturk HK, Prokop LJ, Alahdab F, Foster MA, Lord JM, Karavitaki N, Wass JA, Murad MH, Arlt W, Bancos I (2018) The cortisol stress response induced by surgery: a systematic review and meta-analysis. Clin Endocrinol (oxf) 89:554–567
Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL, Bandera EV, Hamilton KK, Grant B, McCullough M, Byers T, Gansler T (2012) Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62:243–274
Schmid D, Leitzmann MF (2015) Cardiorespiratory fitness as predictor of cancer mortality: a systematic review and meta-analysis. Ann Oncol 26:272–278
Schmidt K, Vogt L, Thiel C, Jäger E, Banzer W (2013) Validity of the six-minute walk test in cancer patients. Int J Sports Med 34:631–636
Shi J, Luo D, Weng H, Zeng X-T, Lin L, Chu H, Tong T (2020) Optimally estimating the sample standard deviation from the five-number summary. Res Synth Methods 11:641–654
Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A (2020) Colorectal cancer statistics, 2020. CA Cancer J Clin 70:145–164
Silver JK, Baima J (2013) Cancer prehabilitation: an opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes. Am J Phys Med Rehabil 92:715–727
Singh F, Galvão DA, Newton RU, Spry NA, Baker MK, Taaffe DR (2018) Feasibility and preliminary efficacy of a 10-week resistance and aerobic exercise intervention during neoadjuvant chemoradiation treatment in rectal cancer patients. Integr Cancer Ther 17:952–959
Snowden CP, Prentis J, Jacques B, Anderson H, Manas D, Jones D, Trenell M (2013) Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people. Ann Surg 257:999–1004
Steffens D, Beckenkamp PR, Young J, Solomon M, da Silva TM, Hancock MJ (2019) Is preoperative physical activity level of patients undergoing cancer surgery associated with postoperative outcomes? A systematic review and meta-analysis. Eur J Surg Oncol 45:510–518
Strous MTA, Janssen-Heijnen MLG, Vogelaar FJ (2019) Impact of therapeutic delay in colorectal cancer on overall survival and cancer recurrence - is there a safe timeframe for prehabilitation? Eur J Surg Oncol 45:2295–2301
Tew GA, Ayyash R, Durrand J, Danjoux GR (2018) Clinical guideline and recommendations on pre-operative exercise training in patients awaiting major non-cardiac surgery. Anaesthesia 73:750–768
van Rooijen SJ, Molenaar CJL, Schep G, van Lieshout RHMA, Beijer S, Dubbers R, Rademakers N, Papen-Botterhuis NE, van Kempen S, Carli F, Roumen RMH, Slooter GD (2019) Making patients fit for surgery: introducing a four pillar multimodal prehabilitation program in colorectal cancer. Am J Phys Med Rehabil 98:888–896
Vonlanthen R, Slankamenac K, Breitenstein S, Puhan MA, Muller MK, Hahnloser D, Hauri D, Graf R, Clavien P-A (2011) The impact of complications on costs of major surgical procedures: a cost analysis of 1200 patients. Ann Surg 254:907–913
Waller E, Sutton P, Rahman S, Allen J, Saxton J, Aziz O (2022) Prehabilitation with wearables versus standard of care before major abdominal cancer surgery: a randomised controlled pilot study (trial registration: NCT04047524). Surg Endosc 36:1008–1017
Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135
Waterland JL, McCourt O, Edbrooke L, Granger CL, Ismail H, Riedel B, Denehy L (2021) Efficacy of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery: a systematic review and meta-analysis. Front Surg 8:628848
West MA, Loughney L, Lythgoe D, Barben CP, Sripadam R, Kemp GJ, Grocott MPW, Jack S (2015) Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study. Br J Anaesth 114:244–251
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Concept, idea and research design were conducted by RF and IG. Writing by RF, CB, and IG. Data collection by RF, CB and JL. Data analysis by RF and CB. Data interpretation by RF, CB, JL, MB, RT and IG. All authors contributed to the critical review of the manuscript before submission.
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Falz, R., Bischoff, C., Thieme, R. et al. Effects and duration of exercise-based prehabilitation in surgical therapy of colon and rectal cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 148, 2187–2213 (2022). https://doi.org/10.1007/s00432-022-04088-w
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DOI: https://doi.org/10.1007/s00432-022-04088-w