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. 2022 May 19;5(5):CD013259.
doi: 10.1002/14651858.CD013259.pub2.

Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery

Charlotte Jl Molenaar  1 , Stefan J van Rooijen  1 , Hugo Jp Fokkenrood  2 , Rudi Mh Roumen  1 , Loes Janssen  1 , Gerrit D Slooter  1
Affiliations

Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery

Charlotte Jl Molenaar et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes.

Objectives: To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer.

Search methods: We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021.

Selection criteria: We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VO2peak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities.

Data collection and analysis: Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible.

Main results: We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. Prehabilitation may also result in fewer complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250) and fewer emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250). The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. On the other hand, prehabilitation may also result in a higher re-admission rate (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250). The certainty of evidence was again low due to downgrading for risk of bias and imprecision. The effect on VO2peak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies.

Authors' conclusions: Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. Complication rates and the number of emergency department visits postoperatively may also diminish due to a prehabilitation programme, while the number of re-admissions may be higher in the prehabilitation group. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.

Trial registration: ClinicalTrials.gov NCT02586701 NCT02502760 NCT01356264 NCT02299596 NCT03096951 NCT03097224 NCT04167436 NCT04595604.

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Conflict of interest statement

No conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
6MWT four weeks postoperatively: post‐intervention scores four weeks postoperatively were used in this analysis. Data for all patients included in the study of Carli 2020 were available for analysis 1.3, 1.5 and 1.6, while data for a various number of patients are missing in analysis 1.1 and 1.4
5
5
6MWT eight weeks postoperatively: in contrast with analysis 1.1 mean change from baseline instead of post‐intervention scores eight weeks postoperatively were used for this analysis.
6
6
Number of patients with complication Data for all patients included in the study of Carli 2020 were available for analysis 1.3, 1.5 and 1.6, while data for a various number of patients are missing in analysis 1.1 and 1.4
7
7
6MWT presurgery: for this analysis both post‐intervention scores (Carli 2020) and mean change from baseline (Bousquet‐Dion 2018 and Gillis 2014) were used. Data for all patients included in the study of Carli 2020 were available for analysis 1.3, 1.5 and 1.6, while data for a various number of patients are missing in analysis 1.1 and 1.4
8
8
Emergency department visits Data for all patients included in the study of Carli 2020 were available for analysis 1.3, 1.5 and 1.6, while data for a various number of patients are missing in analysis 1.1 and 1.4
9
9
Readmissions Data for all patients included in the study of Carli 2020 were available for analysis 1.3, 1.5 and 1.6, while data for a various number of patients are missing in analysis 1.1 and 1.4
1.1
1.1. Analysis
Comparison 1: Prehabilitation versus control, Outcome 1: 6MWT four weeks postoperatively
1.2
1.2. Analysis
Comparison 1: Prehabilitation versus control, Outcome 2: 6MWT eight weeks postoperatively
1.3
1.3. Analysis
Comparison 1: Prehabilitation versus control, Outcome 3: Number of patients with complication
1.4
1.4. Analysis
Comparison 1: Prehabilitation versus control, Outcome 4: 6MWT presurgery
1.5
1.5. Analysis
Comparison 1: Prehabilitation versus control, Outcome 5: Emergency department visits
1.6
1.6. Analysis
Comparison 1: Prehabilitation versus control, Outcome 6: Re‐admissions
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

Bousquet‐Dion 2018 {published data only}
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References to studies excluded from this review

Awasthi 2019 {published data only}
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Ommundsen 2017 {published data only}
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Onerup 2017 {published data only}
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Trépanier 2019 {published data only}
    1. Trépanier M, Minnella EM, Paradis T, Awasthi R, Kaneva P, Schwartzman K, et al.Improved disease-free survival after prehabilitation for colorectal cancer surgery. Annals of Surgery 2019;270(3):493-501. [DOI: 10.1097/SLA.0000000000003465] - DOI - PubMed
Zhang 2014 {published data only}
    1. Zhang M, Chan SW, You L, Wen Y, Peng L, Liu W, et al.The effectiveness of a self-efficacy-enhancing intervention for chinese patients with colorectal cancer: a randomized controlled trial with 6-month follow up. International Journal of Nursing Studies 2014;51(8):1083-92. [DOI: 10.1016/j.ijnurstu.2013.12.005] - DOI - PubMed

References to studies awaiting assessment

NCT03096951 {unpublished data only}
    1. NCT03096951.Prehabilitation in colorectal cancer [Prehabilitation before surgery in colorectal cancer with improved fast track rehabilitation: part 1]. clinicaltrials.gov/ct2/show/NCT03096951 (first received 30 March 2017).

References to ongoing studies

NCT03097224 {unpublished data only}
    1. NCT03097224.Prehabilitation in frail colon cancer [Prehabilitation before surgery in colorectal cancer with improved fast track rehabilitation: part 2]. clinicaltrials.gov/ct2/show/NCT03097224 (first received 31 March 2017).
NCT04167436 {unpublished data only}
    1. NCT04167436.Fit for surgery. MultimodalpPrehabilitation in colorectal cancer patients [Fit for surgery. Clinical randomized trial of multimodal prehabilitation strategy in patients with colorectal cancer]. clinicaltrials.gov/ct2/show/NCT04167436 (first received 18 November 2019).
NCT04595604 {unpublished data only}
    1. NCT04595604.Long term effect of trimodal prehabilitation compared to ERAS in colorectal cancer surgery. (Prehab_2) [Long term effect of trimodal prehabilitation compared to ERAS in colorectal cancer surgery]. clinicaltrials.gov/ct2/show/NCT04595604 (first received 20 October 2020).
NL5784 {unpublished data only}NL5784
    1. NL5784.Prehabilitation for bowel cancer patients undergoing surgery to improve fitness and reduce complications [Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and lower postoperative complications]. trialregister.nl/trial/5784 (first received 01 August 2016).

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