
==== Front
Support Care Cancer
Support Care Cancer
Supportive Care in Cancer
0941-4355
1433-7339
Springer Berlin Heidelberg Berlin/Heidelberg

39287834
8875
10.1007/s00520-024-08875-8
Review
Effect of prehabilitation programmes on functional capacity in patients awaiting oncological resections: a systematic review and meta-analysis of randomised controlled trials
http://orcid.org/0000-0002-6735-2778
Laza-Cagigas Roberto 13
http://orcid.org/0000-0002-8949-0602
Larumbe-Zabala Eneko 2
http://orcid.org/0000-0003-4262-0526
Rampal Tara 3
http://orcid.org/0000-0003-1637-6670
Seijo Marcos 1
http://orcid.org/0000-0001-7405-4894
Naclerio Fernando f.j.naclerio@greenwich.ac.uk

1
1 https://ror.org/00bmj0a71 grid.36316.31 0000 0001 0806 5472 Institute for Lifecourse Development, Centre for Exercise Activity and Rehabilitation, School of Human Science, University of Greenwich, Sparrows Farm (Office SF112B), Sparrows Lane, Avery Hill Campus, Eltham, SE9 2TB England, UK
2 Department of Public Health, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Las Palmas de Gran Canaria, Spain
3 QuestPrehab, London, UK
17 9 2024
17 9 2024
2024
32 10 6677 3 2024
11 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Purpose

To investigate the effects of prehabilitation on the perioperative functional capacity of patients awaiting oncological resections.

Methods

A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and within the databases Cochrane Library, EBSCOhost, Google Scholar, MEDLINE PubMed, and Web of Science. The eligibility criteria were set to include peer-reviewed randomised control trials including only adult (≥ 18 years old) patients undergoing any type of prehabilitation (PREHAB) prior to any type of oncological resection. The studies had to feature at least one control group undergoing standard care (SC) and had to assess functional capacity by means of a 6-min walk distance (6MWD) or peak oxygen uptake (VO2Peak) at different stages pre- and post- operatively.

Results

Twenty-seven randomised controlled trials involving 1994 patients were included. After processing the data, the number of patients was 1889. Studies featured different cancer specialties: lung (11), colorectal (5), urological (4), abdominal (3), esophagogastric (2), liver (1), and gastrointestinal (1). Overall, PREHAB enhanced both 6MWD (g = 0.273, 95% CI 0.174 to 0.371, Z = 5.406, p < 0.001) and VO2Peak (g = 0.615, 95% CI 0.243 to 0.987, Z = 3.240, p = 0.001) compared with SC. The 6MWD subgroup analysis revealed a small mean effect size favouring both unimodal and multimodal PREHAB interventions.

Conclusion

These findings support that prehabilitation, whether implemented as unimodal or multimodal format, elicits small preoperative improvements in functional capacity in patients awaiting oncological resections.

PROSPERO registration number CRD42023428676.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00520-024-08875-8.

Keywords

Cancer
Surgery
Exercise
issue-copyright-statement© Springer-Verlag GmbH Germany, part of Springer Nature 2024
==== Body
pmcIntroduction

The term prehabilitation (PREHAB) refers to the process of optimising patient health prior to surgery with the intention of improving postoperative outcomes [1]. Recently, some researchers and healthcare professionals have advocated for the implementation of consensuses nationally [2] and internationally [3] to determine the characteristics that preoperative PREHAB programmes should comprise. In this respect, in the UK, the incorporation of PREHAB into the pathway of patients expecting oncological resections has gained popularity and is currently being recommended as an effective approach to palliate the side-effects of non-surgical cancer treatment [2].

Prehabilitation programmes can comprise one component (e.g., physical exercise) or more than one (e.g., nutritional advice and psychological support), being referred to as unimodal and multimodal PREHAB, respectively. Furthermore, prehabilitation can be presented in various formats: in person and digitally; one-to-one and in groups; supervised and non-supervised; in the community, the hospital, and at home; and as a combination of all the above. This implies that although PREHAB might be the most prevalent term at the moment, any intervention conducted before surgery with the intention of improving patients’ overall health in preparation for surgery would fit the definition even when the term “prehabilitation” is not explicitly used (e.g., preoperative rehabilitation, nutritional therapy). The recent proliferation of publications covering PREHAB helps to obtain a deeper understanding of its potential benefits. In fact, recent studies have suggested that PREHAB may improve patients’ preoperative fitness [4, 5], and clinical outcomes [6, 7], which may in turn translate into reduced hospital costs [8, 9].

Previous randomised controlled trials and systematic reviews have investigated the effects PREHAB may elicit on, amongst other aspects, postoperative outcomes (e.g., mortality) and functional capacity [10–20]. Functional capacity reflects the ability to perform activities of daily living that require sustained aerobic metabolism [21], and has been commonly assessed by means of the maximum distance covered in 6 min (6MWD), or the maximum or peak oxygen uptake (i.e., VO2max and VO2Peak, respectively) attained during a cardiopulmonary exercise test. It has been shown that oxygen demands are increased during the postoperative period and higher functional capacity can improve postoperative outcomes [22]. Therefore, if preoperative PREHAB programmes improve patients’ functional capacity prior to oncological resections, this intervention could also improve postoperative outcomes. A systematic review with broad eligibility criteria is needed to ascertain whether PREHAB improves preoperative functional capacity in patients diagnosed with cancer and expecting surgery as part of their cancer treatment.

The aim of this systematic review and meta-analysis was to summarise the effect that prehabilitation can elicit on functional capacity in patients awaiting oncological resections.

Methods

This review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist [23] and registered with the International Prospective Register of Systematic Reviews, PROSPERO (CRD42023428676).

Search strategy

The procedures for the current systematic review and meta-analysis included: identification, screening, eligibility, and inclusion/exclusion of studies. A systematic search of the literature with no lower date limit was conducted by two reviewers (RLC and FN) within the following databases: Cochrane Library, EBSCOhost, Google Scholar, MEDLINE PubMed, and Web of Science, through January 2023 to May 2023. Articles had to be written in either English or Spanish.

Applying our search criteria, we identified all randomised controlled trials (RCT) addressing PREHAB in patients undergoing surgery as treatment for cancer. Our search results were supplemented by a manual search of studies included in previously published systematic reviews and meta-analysis [10–20] to ensure that all eligible studies had been included. Resources, without any assigned DOI, commentaries, reviews, or duplicate publications from the same study, were not included. The reference lists of the retrieved studies were hand-searched to identify potentially eligible studies not captured by the electronic searches. Two reviewers (RLC and FN) independently screened the title, abstract, and reference list of each study to locate potentially relevant studies. Any discrepancies between the two authors were resolved through consensus or by the opinion of a third author (ELZ).

Combinations of the following keywords were used as search terms: “(operation OR operative OR surgical OR surgery) AND (cancer OR oncological OR oncology) AND (prehabilitation OR physical activity OR exercise OR nutrition OR oral supplements OR supplementation OR oral nutritional supplements)”. After each search, duplicated records were removed.

Eligibility criteria

We used the Population, Intervention, Comparison, and Outcomes (PICO) framework to determine the eligibility of the studies as follows:

Population

We considered studies on adults (age ≥ 18 years) of any sex, diagnosed with any cancer, and expecting surgery as curative treatment, with or without neoadjuvant therapy, independently of whether they smoked or drank alcohol.

Intervention

Eligible studies could feature PREHAB programmes with the following characteristics: unimodal (e.g., nutrition or physical exercise or anxiety coping strategies) and/or multimodal; supervised and/or non-supervised; face-to-face and/or virtual; hospital-, community-, and/or home-based; delivered to groups of patients and/or individually. The length of the PREHAB programme had to be at least 1 week.

Comparator

We included published, peer reviewed RCT with two or more arms, with at least one arm following a PREHAB programme (intervention group) and another group following the usual or standard care (control group).

Outcomes

Studies were considered for inclusion if they reported measurements of functional capacity (i.e., 6MWD and/or VO2Peak) at different time points during the study.

Studies including patients with and without cancer were included only if they met the rest of the eligibility criteria and data from only those patients diagnosed with cancer were successfully retrieved after contacting the authors.

Study records

Data management and selection

Potentially relevant articles were selected by (i) screening the titles; (ii) screening the abstracts; and (iii) if abstracts did not provide sufficient data, the entire article was retrieved and screened to determine whether it met the inclusion criteria. When data were not presented in the desired format or accurately (i.e., as figures or graphs), we contacted the corresponding authors to request the data. If no answer was obtained, available figures/graphs were analysed using the PDF Adobe Acrobat Pro software measuring tool and means and standard deviations were estimated from medians and interquartile ranges using methods described elsewhere [24]. Where studies matched the selection criteria but included both patients with and without cancer, we contacted the authors to retrieve the data pertaining to only patients with cancer. Thereafter, RLC and FN decided whether the selected articles matched and fitted the purpose of the systematic review.

Data collection process and coding

Data were independently extracted by two authors (RLC and FN) using a standardised data extraction sheet, and any disputes were discussed and settled by a third author (ELZ). The following qualitative and quantitative information was extracted from each included study: (1) authors; (2) publication year; (3) cancer speciality (e.g., prostate, lung, colorectal, breast, etc.); (4) baseline population characteristics; (5) characteristics of the PREHAB intervention, including its duration and components; (6) control procedures; (7) blinding; (8) sample size per group; (9) group means and standard deviations (SD) for functional capacity outcomes at all the available time points. Mean and SD were requested from the corresponding authors when only other statistics were reported (e.g., median, and interquartile range).

Risk of bias in individual studies

Methodological information regarding the potential impact of bias was critically examined. For each study, seven domains from the Cochrane collaboration tool for assessing the risk of bias [25] were scored with high, low, or unclear risk for bias: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and similarity in baseline characteristics. These domains aim to assess the level of risk regarding different sources of bias, respectively: selection bias, allocation bias, performance bias, detection bias, attrition bias, reporting bias, and other biases. Two reviewers (FN and RLC) performed the quality assessment independently, and their findings were compared and discussed until consensus was achieved. Each domain was scored as − 1 for high risk, 0 for unclear risk, and 1 for low risk. Scores were then summed with a possible range of scores from − 7 to 7.

Data analysis

The Comprehensive Meta-Analysis Software, version 4.0.000 (Biostat Inc., Englewood, New York, USA), was used to perform the meta-analysis, the sensitivity analyses, and the publication bias analysis, and to generate forest and funnel plots. The random-effects model was selected based on the assumption of variability in the true effects between studies. Five or more studies were required to generate weighted group mean differences, 95% confidence intervals (CIs), p-values and prediction intervals, for the effect size (Hedges’ g). From the collected data, we used the means, standard deviations (SD), and sample sizes, available at different points in time (e.g., baseline, preoperative, postoperative) for both the PREHAB and the standard care (SC) groups. The primary meta-analysis compared the effects of any PREHAB intervention versus SC in 6MWD and VO2Peak measured pre- and post-operatively. When possible, we conducted a subgroup analysis to evaluate the effect of PREHAB programmes whether they had been applied using a unimodal, or multimodal format. All primary and secondary effect sizes were interpreted using Cohen’s convention for small (0.2), medium (0.5), and large (0.8) effects [26, 27].

When a quantitative analysis was not possible, a summary of the critical facts and results of the observed outcomes was reported. If sensitivity analyses were significantly high, the data were not meta-analysed and only the individual results were reported instead. Additionally, the presence of studies with inflated standardised residual values (> 1.96 or <  − 1.96) was examined to consider them as outliers. Funnel plots of effect size (horizontal-axis) by the standard error (vertical-axis), and the “trim and fill” procedure for the random effects were used to assess publication bias.

Results

Study selection

The search strategy is described in Fig. 1. The preliminary search identified 2313 relevant references. After examining all the retrieved records and deleting duplicates and other non-relevant records, 1033 publications were screened. Of those, 956 were excluded based on the title or abstract review, and the 77 records left were assessed for eligibility. After this examination, 50 studies were excluded resulting in a total of 27 studies [4–7, 28–50] to be included in the meta-analysis.Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for study selection

Characteristics of the included studies

The overall quality of the included studies was high, with a low risk of bias, scoring from 1 to 5 points in the Cochrane collaboration tool [51]. The risk of bias for the 6MWD and the VO2Peak is summarised in Fig. 2 and Fig. 3, respectively. The main characteristics of the studies are summarised in Table 1.Fig. 2 6-min walk distance risk of bias summary based on the Cochrane collaboration tool

Fig. 3 Peak oxygen uptake (VO2Peak) risk of bias summary based on the Cochrane collaboration tool

Table 1 Summary of the randomised controlled trials included in the meta-analysis

Study	Design	Participants	Length	Intervention	Measurements	Outcomes	
Allen et al. [40]	Two parallel arms

PREHAB (n = 26), SC (n = 28)

	Esophagogastric; ≥ 18 y/o

n = 54

	15 Weeks	Exercise: aerobic, resistance, and flexibility training

Nutritional: frequent, tailored, dietetic input

Psychological: medical coaching with psychotherapist

	VO2Peak	↑	
Banerjee et al. [41]	Two parallel arm, feasibility, single-centre PREHAB (n = 30), SC (n = 30)	Bladder

n = 60

	mean SD

32 (6.5) days

	Exercise: vigorous intensity interval aerobic training	VO2Peak	 → 	
Barberan-Garcia et al. [48]	Blind, parallel arms

PREHAB (n = 62), SC (n = 63)

	Abdominal

 > 70 y/o

n = 125

	6 weeks	Exercise intervention: aerobic and resistance training

Psychological: motivational interview

	6MWD	?	
Bausys et al. [49]	Two parallel arm, open-label, two centres

PREHAB (n = 61), SC (n = 61)

	Gastrointestinal

 ≥ 18 y/o

n = 122

	mean (SD)

92 (33) days

	Exercise: aerobic, respiratory, resistance, and flexibility training

Nutritional: nutritional counselling, ONS

Psychological: oncopsychologist, relaxations techniques to do at home

	6MWD

VO2max

	↑	
Blackwell et al. [28]	Two parallel arms

PREHAB (n = 19), SC (n = 21)

	Urological

n = 40

	median [IQR]

30 [26–30] days

	Exercise: supervised HIIT training	VO2Peak	↑	
Bousquet-Dion et al. [29]	Two parallel-arm

PREHAB + REHAB (n = 37), REHAB (n = 26)

	Colorectal

Adults

n = 63

	PREHAB: 4 weeks

REHAB: 8 weeks

	Exercise: aerobic and resistance training

Nutritional: WPS, nutritional counselling

Psychological: psychology-trained staff, exercises to do at home

	6MWD	 → 	
Carli et al. [30]	Two parallel arms, 2-site, single-blind

PREHAB (n = 55)

REHAB (n = 55)

	Colorectal

 ≥ 65 y/o

Fried Frailty Index > 1

n = 110

	PREHAB: 4 weeks

REHAB: 4 weeks

	Exercise: aerobic and resistance training

Nutritional: WPS, Nutritional counselling

Psychological: psychology-trained staff, exercises to do at home

	6MWD	 → 	
Dunne et al. [42]	Two parallel arms

PREHAB (n = 20), SC (n = 18)

	Liver

 ≥ 18 y/o

n = 37

	4 weeks	Exercise: interval training	VO2Peak	↑	
Ferreira et al. (a) [32]	Two parallel arm, single-blind

PREHAB + REHAB (n = 52), REHAB (n = 43)

	Lung

Adult patients

n = 95

	PREHAB: 4 weeks

REHAB: 8 weeks

	Exercise: aerobic and resistance training

Nutritional: WPS, counselling

Psychological: psychology-trained staff, exercises to do at home

	6MWD	 → 	
Ferreira et al. (b) [31]	Two parallel arms, open-label

PREHAB (n = 24), SC (n = 10)

	Lung

Adult patients

n = 34

	4 weeks	Exercise: aerobic and resistance training

Nutritional: WPS, counselling, EPA, DHA, and Vit. D3 supplementation

Psychological: psychology-trained staff, exercises to do at home

	6MWD	 → 	
Gillis et al. [33]	Two parallel arm, single-blind

PREHAB + REHAB (n = 38), REHAB (n = 39)

	Colorectal

Adult patients

n = 77

	PREHAB: 4 weeks

REHAB: 8 weeks

	Exercise: aerobic and resistance training

Nutritional: WPS, counselling

Psychological: psychology-trained staff, exercises to do at home

	6MWD	↑	
Huang et al. [7]	Three parallel arms

PREHAB1 (n = 30), PREHAB2 (n = 30), SC (n = 30)

	Lung

n = 90

	1 week	Exercise (PREHAB1): aerobic and respiratory training

Exercise (PREHAB2): respiratory training

	6MWD	↑	
Karenovics et al. [43]	Two parallel arms, prospective, open blinded end point

PREHAB (n = 74), SC (n = 77)

	Lung

 ≥ 18 years old

n = 151

	median [IQR]

26 [12, 21–32] days

	Exercise: HIIT	VO2Peak

6MWD*

	↑	
Karlsson et al. [50]	Two parallel arm, feasibility study

PREHAB (n = 10), SC (n = 11)

	Colorectal

 ≥ 70 y/o

n = 21

	median (range)

17 (14–24) days

	Exercise: aerobic, resistance, and respiratory training	6MWD	?	
Lai et al. (a) [6]	Two parallel arms, single-blind

PREHAB (n = 30), SC (n = 30)

	Lung

 ≥ 70 y/o

n = 60

	1 week	Exercise: aerobic and respiratory training	6MWD	↑	
Lai et al. (b) [44]	Two parallel arms, single-blind

PREHAB (n = 51), SC (n = 50)

	Lung

 > 75 y/o

n = 101

	1 week	Exercise: aerobic and respiratory training	6MWD	↑	
Liu et al. [34]	Two parallel arms, single-blind

PREHAB (n = 37), REHAB (n = 36)

	Lung

 < 70 y/o

n = 73

	2 weeks	Exercise: aerobic, resistance, and respiratory training

Nutritional: WPS, counselling

Psychological: exercises to do at home

	6MWD	↑	
Ma et al. [45]	Three parallel arms, pilot, single-centre, single-blind

PREHAB1 (n = 34), PREHAB2 (n = 32), SC (n = 35)

	Lung

 ≥ 70 y/o

n = 101

	2 weeks	Exercise (PREHAB1): aerobic and respiratory training

Exercise (PREHAB2): respiratory training

	6MWD	↑	
Minnella et al. [4]	Two parallel arms, pragmatic, single-blind

PREHAB (n = 26), SC (n = 25)

	Esophagogastric

 ≥ 70 y/o

n = 51

	mean (SD)

42 (43.92) days

	Exercise: aerobic and resistance training

Nutritional: WPS, counselling

	6MWD	↑	
Molenaar et al. [35]	Two parallel arms, open-label, international, multicentre, single-blind

PREHAB (n = 123), SC (n = 128)

	Colorectal

Adult patients

n = 251

	4 weeks	Exercise: resistance and HIIT

Nutritional: WPS, counselling, Vit. D and multinutrient supplementation

Psychological: psychology-trained staff, exercises to do at home, psychologist referral is required

	6MWD	↑	
Morano et al. [46]	Two parallel arms, single-blind

PREHAB (n = 12), SC (n = 12)

	Lung

Patients with previous respiratory disease and impaired respiratory function spirometry

n = 24

	4 weeks	Exercise: aerobic, PNF, and respiratory training	6MWD	↑	
Moug et al. [47]	Two parallel arms, feasibility study

PREHAB (n = 24), SC (n = 24)

	Colorectal (rectal)

 > 18 y/o

n = 48

	median [IQR]

14 [13–17] weeks

	Exercise: aerobic training	6MWD	?	
Santa Mina et al. [36]	Two parallel arm, PREHAB (n = 44), SC (n = 42)	Prostate

40–80 y/o

n = 86

	mean (SD)

45 (27) days

	Exercise: aerobic, resistance, and pelvic floor training	6MWD	↑	
Sebio Garcia et al. [37]	Two parallel arms, single-blind

PREHAB (n = 10), SC (n = 12)

	Lung

 ≥ 18 y/o

FEV1 ≤ 80% and/or

BMI ≥ 30 and/or age ≥ 75 years and/or two or more co-morbidities identified in the Colinet Comorbidity Score

n = 22

	mean (SD)

54.5 (15.4) days

	Exercise: aerobic, resistance, and respiratory training	6MWD	 → 	
Stefanelli et al. [5]	Two parallel arms

PREHAB (n = 20), SC (n = 20)

	Lung

n = 40

	3 weeks	Exercise: upper and lower body aerobic and respiratory training	VO2Peak	↑	
Steffens et al. [38]	Two parallel arms, pilot, single-centre, single-blind

PREHAB (n = 11), SC (n = 11)

	Abdominal

18–80 y/o

n = 22

	2–6 weeks	Exercise: aerobic and resistance training	6MWD	 → 	
Waller et al. [39]	Two parallel arms, pilot, single-centre

PREHAB (n = 11), SC (n = 11)

	Abdominal

 ≥ 18 y/o

n = 22

	mean (SD)

30.5 (19.8) days

	Exercise: aerobic and resistance training

Nutritional: Educational material, Fitbit used to log food and protein

Psychological: Mindful session via smartphone app

	6MWD	↑	
6MWD, 6-min walk distance; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HIIT, high-intensity interval training; IQR, interquartile range; ONS, oral nutritional supplement, PNF, proprioceptive neuromuscular facilitation; PREHAB, prehabilitation; REHAB, rehabilitation; SC, standard care; SD, standard deviation; Vit., vitamin; WPS, whey protein supplementation; ↑, beneficial effects from Prehab; → , no beneficial effects from Prehab; ?, no conclusion reported

All the studies included patients awaiting surgery for a total of 1994 patients (Fig. 1). Twenty-five studies included one PREHAB group, and another two studies included two PREHAB groups. Group sizes ranged from 10 to 128 patients. In the PREHAB group, group sizes ranged from 10 to 132 patients, with a total of 1040 patients, and in the SC group, groups sizes ranged from 10 to 128, with a total of 954 patients. After selecting patients diagnosed with cancer, and with data available at baseline and at least one more time point (e.g., prior to surgery), the total number of patients was reduced to 1889. In terms of the treatment undergone by patients, twelve studies (44%) included patients undergoing surgery only, while fourteen (52%) included patients undergoing neoadjuvant chemotherapy prior to surgery. Excluding one study (4%), which enrolled patients awaiting prostatectomy, the rest of the studies (96%) included both female and male patients. Studies reported on patients with lung cancer (n = 11; 41%), colorectal cancer (n = 5; 19%), abdominal cancer (n = 3; 11%), esophagogastric cancer (n = 2; 7%), liver cancer (n = 1; 4%), prostate cancer (n = 1; 4%), bladder cancer (n = 1; 4%), urological cancer (n = 1; 4%), and gastrointestinal cancer (n = 1; 4%). Most of the studies compared PREHAB interventions with SC (n = 23; 85%), followed by studies comparing a PREHAB and rehabilitation intervention with only rehabilitation (n = 3; 11%), and studies comparing a PREHAB with rehabilitation (n = 1; 4%). Due to the nature of the non-PREHAB groups, the latter four studies were only included in the meta-analysis comparing preoperative changes in 6MWD. In respect of the length of PREHAB interventions, six (21%) lasted from 1 to 2 weeks, thirteen (45%) lasted from 3 to 4 weeks, and ten (34%) lasted more than 4 weeks. There was an almost equal distribution of studies implementing unimodal (n = 14; 52%) and multimodal (n = 13; 48%) PREHAB interventions. The exercise component was included in all the studies (100%), nutrition in ten (37%), and psychological support in nine studies (33%). Most of the studies assessed functional capacity at least twice preoperatively (n = 26; 96%) and only one (4%) did not assessed functional capacity right before surgery. When adherence or compliance where reported (n = 21; 78%), their definition differed amongst studies. Therefore, we could not objectively summarise such outcomes. The 6MWD walk distance was used to measured functional capacity in twenty-two studies (81%) while VO2Peak was used in seven (26%). To summarise the effects of PREHAB on functional capacity, most of the studies (n = 17; 63%) reported beneficial effects of PREHAB over SC, followed by studies reporting no differences (n = 7; 26%), and studies where data were provided with no reported conclusion (n = 3; 11%).

Changes on the analysed variables

Preoperative changes in 6MWD

From the 21 studies analysing 6MWD, the mean effect size of PREHAB vs. SC was found to be small (g = 0.273, 95% CI 0.174 to 0.371) (Fig. 4). The sensitivity analysis showed that none of the studies contributed disproportionately to the results of the meta-analysis. We did not identify any outlier amongst the analysed studies. Inspection of funnel plots revealed more studies to the right of the mean (Online Resource 1). Applying the “trim and fill” procedure, 6 studies were added to the left of the mean, which resulted in an adjusted mean effect size of 0.183 (95% CI 0.064 to 0.301), still showing a positive effect size.Fig. 4 6MWD distance Forest plot. Results of a random-effects meta-analysis showed the effect size (g) with 95% confidence interval. The black diamonds represent the subgroups (unimodal or multimodal) standardised mean differences and the white diamond the pooled (overall) standardised mean differences. 6MWD, 6-min walk distance; CI, confidence interval

The subgroup analysis revealed a small mean effect size for both unimodal (g = 0.318, 95% CI 0.159 to 0.476) and multimodal (g = 0.244, 95% CI 0.118 to 0.370) PREHAB interventions (Fig. 4). The analysis also revealed no statistically significant differences between unimodal and multimodal interventions (Q(1) = 0.505, p = 0.477).

Preoperative changes in VO2Peak

From the 7 studies analysing VO2Peak, the mean effect size of PREHAB vs. SC was found to be medium (g = 0.615, 95% CI 0.243 to 0.987) (Fig. 5). The prediction interval was calculated from -0.562 to 1.793 (95% CI). The sensitivity analysis showed that none of the studies contributed disproportionately to the results of the meta-analysis. No outliers were identified amongst the analysed studies. Inspection of funnel plots revealed one study more to the left of the mean when compared with the number of studies to the right of the mean (Online Resource 2). However, when applying the “trim and fill” procedure, no studies were added to either side of the mean. Due to the small number of eligible studies, we did not perform any subgroup analysis for this variable.Fig. 5 VO2Peak Forest plot. Results of a random-effects meta-analysis showed the effect size (g) with 95% confidence interval. The white diamond represents the pooled (overall) standardised mean differences. CI, confidence interval; VO2Peak, peak oxygen consumption

Postoperative changes in 6MWD and VO2Peak

Since only three eligible studies assessed 6MWD on discharge [38, 45, 50], and three assessed it after discharge [4, 17, 34], no meta-analysis was conducted. Moreover, only two eligible studies assessed change in VO2Peak during the postoperative period [5, 43]. Therefore, no meta-analysis was conducted for this variable either.

Discussion

Compared to preoperative SC, PREHAB led to small preoperative improvements in functional capacity as estimated by the 6MWD test. This effect was shown whether the intervention consisted of multimodal PREHAB (i.e., exercise and other components) or unimodal exercise-based PREHAB. The mean effect of PREHAB on VO2Peak was also positive. However, the prediction interval ranged from a medium negative to a very large positive effect size (Fig. 5). Based on the currently available data, we cannot assert that PREHAB always improves VO2Peak. This uncertainty derives from the low number of eligible studies, their different effect sizes, and the heterogeneity displayed by their PREHAB programmes. In fact, only two of the studies implemented multimodal PREHAB, including exercise, nutrition, and psychological support [40, 49]. The other five studies featured unimodal exercise-based PREHAB and, despite implementing aerobic exercise, the training protocols varied widely amongst studies [5, 28, 41–43]. Interestingly, the studies by Allen et al. [40] and Bausys et al. [49] displayed the least favourable effect size of PREHAB over SC (Fig. 5) despite implementing longer-lasting multimodal PREHAB programmes (ranging from 8 to 15 weeks) (Table 1), compared to the shorter unimodal exercise-based PREHAB programmes (ranging from 3 to 4 weeks) implemented in the rest of the studies.

We considered the possibility of neoadjuvant chemotherapy impacting the effect of PREHAB. Coincidentally, we found that the three studies [5, 28, 43] with the greatest effect size and both 95% CI favouring PREHAB had a low percentage of patients undergoing neoadjuvant chemotherapy, ranging from 0 to 12% (Fig. 5). In contrast, the proportion of patients undergoing neoadjuvant chemotherapy was higher in the other four studies [40–42, 49], ranging from 33 to 100%. The exposure to chemotherapy treatment could hinder the ability of patients to exercise, and consequently to develop the physiological adaptations expected from PREHAB, hence, explaining the different effect size observed between studies. Notwithstanding the potential interference between chemotherapy and PREHAB-induced improvements on functional capacity, exercise-based interventions provide a beneficial immune effect without adding to the common side effects experienced due to chemotherapy treatment [52]. Furthermore, exercise-based interventions could aid to improve the common cancer-related health outcomes such as fatigue, anxiety, depression symptoms, and health-related quality of life [53]. Additionally, the inclusion of resistance training would induce beneficial effects against muscle atrophy, a prevalent side effect of chemotherapy [54]. However, to be beneficial, interventions should be tailored to the individual characteristics of each patient [52] and the training variables should be manipulated to provide the expected physiological adaptations [55].

From a practical perspective, even though no statistical heterogeneity was determined in the analysis of 6MWD, it is worth noticing some methodological differences between the included studies. Exercise-based programmes can vary widely even when implemented as a unimodal intervention. The almost endless number of combinations of exercise modalities (e.g., resistance, aerobic, respiratory training) and configurations of training variables (e.g., volume, intensity, inter-set rest periods, and frequency) contributes to a great diversity of approaches. Therefore, implementing multimodal programmes implies adding more complexity, and potentially increasing the methodological divergence between studies. Indeed, despite all the included studies implemented an exercise component, the difference amongst programmes was evident, with some of them containing exclusively breathing exercises [7, 45] and others combining aerobic, resistance, and breathing exercise [34, 37, 38, 40, 49, 50]. When nutrition was included in the intervention, the most common strategy was individualised nutritional counselling with an emphasis on appropriate protein intake by providing protein supplements [4, 29–35, 49], such as whey concentrates or isolates [4, 29–35]. Other supplements, such as omega-3 fatty acids, vitamin D3, and multi-ingredient formulations [30–32, 35, 49], were also used. Anxiety management strategies were the main focus within the psychological support component [29–35, 39, 40, 47–49]. Due to the scarcity of eligible studies integrating nutrition into multimodal PREHAB, it was difficult to ascertain the effect of nutrition on the functional capacity of surgical oncology patients and whether it can provide similar benefits to exercise-based interventions.

The present meta-analysis is unique due to the chosen eligibility criteria, the rigour of selecting the included studies, and the fact that we have analysed changes in functional capacity (e.g., from baseline to before surgery) instead of analysing static values (e.g., before surgery, post-intervention). Our review included data from patients who had a confirmed diagnosis of cancer with measurements at baseline and at least another time point (e.g., prior to surgery) [48, 50]. Despite methodological differences, our results agree with previous systematic reviews with meta-analyses of RCT supporting the notion that PREHAB can improve patient’s functional capacity prior to oncological resections [10, 11, 13–19].

For instance, meta-analyses of RCTs studying the effect of PREHAB in patients with lung cancer have reported enhancements in their functional capacity [10, 11, 13, 16, 18]. Pu et al. [11] meta-analysed four studies and reported improvements on 6MWD after patients completed preoperative breathing exercises. Moreover, Gravier et al. [13] analysed the effects of aerobically demanding exercise PREHAB programmes finding worthwhile positive effects on 6MWD when comparing PREHAB to SC. Simultaneously, these authors summarised data on VO2Peak and found PREHAB to be beneficial. Furthermore, Cavalheri et al. [10] reported favourable effects of exercise-based PREHAB vs. SC on functional capacity by means of the 6MWD. Along those lines, Li et al. [16] and Rosero et al. [18] found significant differences favouring exercise-based PREHAB interventions when compared to SC as estimated by 6MWD and VO2Peak. Although we included any cancer speciality, the outcomes of our meta-analysis align with the results of the aforementioned reviews, supporting the beneficial effects of PREHAB on functional capacity in patients with lung cancer.

On the other hand, van Gestel et al. [14] reported positive effects of home-based multimodal PREHAB on the functional capacity of patients after oncological resections from any cancer speciality. Compared to control groups receiving SC, PREHAB improved 6MWD pre-surgery and at 8 weeks post-operatively. Similarly, Smyth et al. [20] performed a meta-analysis comparing the effects of high-intensity interval training PREHAB vs. SC in oncological resections. The authors observed non-significant differences between PREHAB and SC on VO2Peak values. Due to our eligibility criteria, we could not analyse the postoperative effects of PREHAB on functional capacity. However, the preoperative outcome analysis reported by van Gestel et al. [14] and Smyth et al. [20] reinforce our findings that the analysis of the included RCT would not unequivocally support that PREHAB improves VO2Peak. Nonetheless, when analysing the impact of PREHAB on 6MWD, we found more robust and consistent evidence that PREHAB can improve preoperative functional capacity vs. SC.

The effects of PREHAB programmes on exercise capacity of surgical gastrointestinal cancer patients have also been studied by Lau et al. [15]. The authors included studies featuring unimodal or multimodal PREHAB programmes. Their preoperative analysis revealed improvements elicited by PREHAB on 6MWD. These findings remained true for their postoperative analysis, at 4–8 weeks after surgery. Our findings and those by Lau et al. [15] support the notion that both unimodal and multimodal PREHAB programmes can improve functional capacity in patients with cancer.

In relation to abdominal oncological resections, Waterland et al. [19] investigated the effect of PREHAB on functional capacity of patients undergoing such procedures. By analysing three studies, the authors observed no significant improvement in VO2Peak. Furthermore, a meta-analysis on 6MWD preoperative changes showed an improvement on 6MWD elicited by PREHAB when compared to SC. Both findings are strengthened by the outcomes of our analysis. Waterland et al. [19] also performed a subgroup analysis for the 6MWD analysis and showed benefits of PREHAB to remain significant for multimodal programmes and, contrary to our findings, non-significant for unimodal programmes. We believe this difference could be due to (a) a more restrictive inclusion criteria (i.e., abdominal oncological resections), (b) the limited number of studies analysed by the authors (two) in contrast with those analysed in our meta-analysis (9 studies, with 11 groups in total), and (c) the inclusion of one study that accepted both patients with cancer and patients with benign disease.

Our results also agree with previous reviews suggesting clinical benefits of PREHAB vs. the SC in patients with colorectal cancer. In this respect, Molenaar et al. [17] reported significant and clinically favourable effects on 6MWD of PREHAB vs. the SC in patients waiting for colorectal resection. In two further analyses, the authors summarised data on 6MWD at 4 and 8 weeks postoperatively and found non-statistically significant benefits of PREHAB over SC. Additionally, our results agree with the meta-analysis by Falz et al. [12] supporting the effects of PREHAB to significantly improve 6MWD in patient awaiting colorectal cancer resections.

Limitations and recommendation for future studies

Several aspects of this review must be considered when attempting to draw evidence-based inferences. The broad inclusion criteria implemented in this review allowed for the analysis of studies including patients from various cancer specialities such as lung, colorectal, abdominal, esophagogastric, liver, urological, and gastrointestinal. Therefore, while the findings of this review may be applied to these types of cancers, caution is granted when considering other cancer specialities (e.g., brain, breast). Future RCT should investigate the effect of PREHAB on functional capacity in patients diagnosed with other cancers not yet explored.

Most of the studies included in our meta-analysis assessed 6MWD as a measurement of functional capacity and only a few used VO2Peak. Although the 6MWD analysis revealed that PREHAB provides a small benefit on functional capacity, the outcomes of the VO2Peak analysis did not show such certainty. We suggest that a greater number of studies assessing VO2Peak could increase statistical power and help to gain insight into the effects of PREHAB on oxygen uptake.

Although this review shows how PREHAB improves preoperative functional capacity, we have not analysed whether this improvement also represents better surgical outcomes. As this is important from a clinical perspective, further research should explore the correlation between preoperative functional capacity changes and surgical outcomes.

In this review, 6MWD and VO2Peak were selected due to being well-recognised measurements of functional capacity. However, the authors recognised the presence of other tests that could also be relevant to assess functional capacity (e.g., timed up-and-go test, 60-s sit-to-stand test). We did not analyse the independent effect that different components could have on functional capacity. As such, we could not ascertain whether nutrition- or psychological-based unimodal PREHAB could be comparable to exercise-based unimodal PREHAB programmes. In this regard, nutrition, and particularly protein intake, could play a major role in retaining lean body mass, which could positively impact functional capacity. Future studies implementing non-exercise-based unimodal PREHAB should assess functional capacity to shed light onto this hypothesis.

Conclusions

Our results show that prehabilitation, whether implemented as unimodal or multimodal format, elicits small preoperative functional capacity improvements in patients awaiting oncological resections. These benefits seem to extend to various tumour groups. Clinicians are encouraged to integrate prehabilitation programmes including at least an exercise component as part of their patients’ cancer care pathway.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 19 KB)

Author contribution

RL and FN conducted the research and wrote the main manuscript text. ELZ supervised all statistical analysis and confirmed the results, TR and MS revised all clinical aspects, and all authors reviewed and approved the manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Milder DA Pillinger NL Kam PCA The role of prehabilitation in frail surgical patients: a systematic review Acta Anaesthesiol Scand 2018 62 1356 1366 10.1111/aas.13239 30094821
Milder DA, Pillinger NL, Kam PCA (2018) The role of prehabilitation in frail surgical patients: a systematic review. Acta Anaesthesiol Scand 62:1356–136630094821
2. MacMillan (2019) Principles and guidance for prehabilitation within the management and support of people with cancer. MacMillan Cancer Support; 2019
3. van Stefanus JR, Molenaar CJLMD, Schep GMD et al (2019) Making patients fit for surgery: introducing a four pillar multimodal prehabilitation program in colorectal cancer. Am J Phys Med Rehabil 98:888–96. Available from: https://search.ebscohost.com/login.aspx?direct=true&AuthType=sso&db=aph&AN=139710443&site=ehost-live&scope=site&custid=s5848088
4. Minnella EM Awasthi R Loiselle S-E Agnihotram RV Ferri LE Carli F Effect of exercise and nutrition prehabilitation on functional capacity in esophagogastric cancer surgery JAMA Surg 2018 153 1081 10.1001/jamasurg.2018.1645 30193337
Minnella EM, Awasthi R, Loiselle S-E, Agnihotram RV, Ferri LE, Carli F (2018) Effect of exercise and nutrition prehabilitation on functional capacity in esophagogastric cancer surgery. JAMA Surg 153:108130193337
5. Stefanelli F Meoli I Cobuccio R Curcio C Amore D Casazza D High-intensity training and cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease and non-small-cell lung cancer undergoing lobectomy Eur J Cardiothorac Surg 2013 44 e260 e265 10.1093/ejcts/ezt375 23892298
Stefanelli F, Meoli I, Cobuccio R, Curcio C, Amore D, Casazza D et al (2013) High-intensity training and cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease and non-small-cell lung cancer undergoing lobectomy. Eur J Cardiothorac Surg 44:e260–e26523892298
6. Lai Y Huang J Yang M Su J Liu J Che G Seven-day intensive preoperative rehabilitation for elderly patients with lung cancer: a randomized controlled trial J Surg Res 2017 209 30 36 10.1016/j.jss.2016.09.033 28032568
Lai Y, Huang J, Yang M, Su J, Liu J, Che G (2017) Seven-day intensive preoperative rehabilitation for elderly patients with lung cancer: a randomized controlled trial. J Surg Res 209:30–3628032568
7. Huang J Lai Y Zhou X Li S Su J Yang M Short-term high-intensity rehabilitation in radically treated lung cancer: a three-armed randomized controlled trial J Thorac Dis 2017 9 1919 1929 10.21037/jtd.2017.06.15 28839990
Huang J, Lai Y, Zhou X, Li S, Su J, Yang M et al (2017) Short-term high-intensity rehabilitation in radically treated lung cancer: a three-armed randomized controlled trial. J Thorac Dis 9:1919–192928839990
8. Sabajo CR ten Cate DWG Heijmans MHM Koot CTG van Leeuwen LVL Slooter GD Prehabilitation in colorectal cancer surgery improves outcome and reduces hospital costs Eur J Surg Oncol 2024 50 107302 10.1016/j.ejso.2023.107302 38043359
Sabajo CR, ten Cate DWG, Heijmans MHM, Koot CTG, van Leeuwen LVL, Slooter GD (2024) Prehabilitation in colorectal cancer surgery improves outcome and reduces hospital costs. Eur J Surg Oncol 50:10730238043359
9. Barberan-Garcia A Ubre M Pascual-Argente N Risco R Faner J Balust J Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial Br J Anaesth 2019 123 450 456 10.1016/j.bja.2019.05.032 31248644
Barberan-Garcia A, Ubre M, Pascual-Argente N, Risco R, Faner J, Balust J et al (2019) Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial. Br J Anaesth 123:450–45631248644
10. Cavalheri V, Granger C (2017) Preoperative exercise training for patients with non-small cell lung cancer. Cochrane Database Syst Rev 2017. 10.1002/14651858.CD012020.pub2
11. Pu CY Batarseh H Zafron ML Mador MJ Yendamuri S Ray AD Effects of preoperative breathing exercise on postoperative outcomes for patients with lung cancer undergoing curative intent lung resection: a meta-analysis Arch Phys Med Rehabil 2021 102 2416 2427.e4 10.1016/j.apmr.2021.03.028 33930327
Pu CY, Batarseh H, Zafron ML, Mador MJ, Yendamuri S, Ray AD (2021) Effects of preoperative breathing exercise on postoperative outcomes for patients with lung cancer undergoing curative intent lung resection: a meta-analysis. Arch Phys Med Rehabil 102:2416-2427.e433930327
12. Falz R, Bischoff C, Thieme R, Lässing J, Mehdorn M, Stelzner S et al (2022) 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(9):2187–2213. 10.1007/s00432-022-04088-w
13. Gravier F-E Smondack P Prieur G Medrinal C Combret Y Muir J-F Effects of exercise training in people with non-small cell lung cancer before lung resection: a systematic review and meta-analysis Thorax 2022 77 486 496 10.1136/thoraxjnl-2021-217242 34429375
Gravier F-E, Smondack P, Prieur G, Medrinal C, Combret Y, Muir J-F et al (2022) Effects of exercise training in people with non-small cell lung cancer before lung resection: a systematic review and meta-analysis. Thorax 77:486–49634429375
14. van Gestel T Groen LCB Puik JR van Rooijen SJ van der Zaag-Loonen HJ Schoonmade LJ Fit4Surgery for cancer patients during covid-19 lockdown – a systematic review and meta-analysis Eur J Surg Oncol 2022 48 1189 1197 10.1016/j.ejso.2022.02.010 35183411
van Gestel T, Groen LCB, Puik JR, van Rooijen SJ, van der Zaag-Loonen HJ, Schoonmade LJ et al (2022) Fit4Surgery for cancer patients during covid-19 lockdown – a systematic review and meta-analysis. Eur J Surg Oncol 48:1189–119735183411
15. 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 10.1007/s11605-019-04436-1 31768827
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 24:2829–283731768827
16. Li X Li S Yan S Wang Y Wang X Sihoe AD Impact of preoperative exercise therapy on surgical outcomes in lung cancer patients with or without COPD: a systematic review and meta-analysis Cancer Manag Res 2019 11 1765 1777 10.2147/CMAR.S186432 30858729
Li X, Li S, Yan S, Wang Y, Wang X, Sihoe AD et al (2019) Impact of preoperative exercise therapy on surgical outcomes in lung cancer patients with or without COPD: a systematic review and meta-analysis. Cancer Manag Res 11:1765–177730858729
17. Molenaar CJ, van Rooijen SJ, Fokkenrood HJ et al (2022) 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. 10.1002/14651858.CD013259.pub2
18. Rosero ID Ramírez-Vélez R Lucia A Martínez-Velilla N Santos-Lozano A Valenzuela PL Systematic review and meta-analysis of randomized, controlled trials on preoperative physical exercise interventions in patients with non-small-cell lung cancer Cancers (Basel) 2019 11 944 10.3390/cancers11070944 31284372
Rosero ID, Ramírez-Vélez R, Lucia A, Martínez-Velilla N, Santos-Lozano A, Valenzuela PL et al (2019) Systematic review and meta-analysis of randomized, controlled trials on preoperative physical exercise interventions in patients with non-small-cell lung cancer. Cancers (Basel) 11:94431284372
19. Waterland JL, McCourt O, Edbrooke L et al (2021) Efficacy of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery: a systematic review and meta-analysis. Front Surg 8. 10.3389/fsurg.2021.628848
20. Smyth E O’Connor L Mockler D Reynolds JV Hussey J Guinan E Preoperative high intensity interval training for oncological resections: a systematic review and meta-analysis Surg Oncol 2021 38 101620 10.1016/j.suronc.2021.101620 34161894
Smyth E, O’Connor L, Mockler D, Reynolds JV, Hussey J, Guinan E (2021) Preoperative high intensity interval training for oncological resections: a systematic review and meta-analysis. Surg Oncol 38:10162034161894
21. Arena R Myers J Williams MA Gulati M Kligfield P Balady GJ Assessment of functional capacity in clinical and research settings Circulation 2007 116 329 343 10.1161/CIRCULATIONAHA.106.184461 17576872
Arena R, Myers J, Williams MA, Gulati M, Kligfield P, Balady GJ et al (2007) Assessment of functional capacity in clinical and research settings. Circulation 116:329–34317576872
22. Rose GA Davies RG Appadurai IR Williams IM Bashir M Berg RMG ‘Fit for surgery’: the relationship between cardiorespiratory fitness and postoperative outcomes Exp Physiol 2022 107 787 799 10.1113/EP090156 35579479
Rose GA, Davies RG, Appadurai IR, Williams IM, Bashir M, Berg RMG et al (2022) ‘Fit for surgery’: the relationship between cardiorespiratory fitness and postoperative outcomes. Exp Physiol 107:787–79935579479
23. Page MJ McKenzie JE Bossuyt PM Boutron I Hoffmann TC Mulrow CD The PRISMA statement: an updated guideline for reporting systematic reviews BMJ 2020 2021 n71
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, The PRISMA et al (2020) statement: an updated guideline for reporting systematic reviews. BMJ 2021:n71
24. Wan X Wang W Liu J Tong T Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range BMC Med Res Methodol 2014 14 135 10.1186/1471-2288-14-135 25524443
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 14:13525524443
25. Higgins JPT Sterne JAC Savovic J Page MJ Hróbjartsson A Boutron I A revised tool for assessing risk of bias in randomized trials Cochrane Methods Cochrane Database Syst Rev 2016 10 29 31
Higgins JPT, Sterne JAC, Savovic J, Page MJ, Hróbjartsson A, Boutron I et al (2016) A revised tool for assessing risk of bias in randomized trials. Cochrane Methods Cochrane Database Syst Rev 10:29–31
26. Cohen J (2013) Statistical power analysis for the behavioral sciences. Routledge
27. Lakens D (2013) Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol 4. 10.3389/fpsyg.2013.00863
28. Blackwell JEM Doleman B Boereboom CL Morton A Williams S Atherton P High-intensity interval training produces a significant improvement in fitness in less than 31 days before surgery for urological cancer: a randomised control trial Prostate Cancer Prostatic Dis 2020 23 696 704 10.1038/s41391-020-0219-1 32157250
Blackwell JEM, Doleman B, Boereboom CL, Morton A, Williams S, Atherton P et al (2020) High-intensity interval training produces a significant improvement in fitness in less than 31 days before surgery for urological cancer: a randomised control trial. Prostate Cancer Prostatic Dis 23:696–70432157250
29. Bousquet-Dion G Awasthi R Loiselle S-È Minnella EM Agnihotram RV Bergdahl A Evaluation of supervised multimodal prehabilitation programme in cancer patients undergoing colorectal resection: a randomized control trial Acta Oncol (Madr) 2018 57 849 859 10.1080/0284186X.2017.1423180
Bousquet-Dion G, Awasthi R, Loiselle S-È, Minnella EM, Agnihotram RV, Bergdahl A et al (2018) Evaluation of supervised multimodal prehabilitation programme in cancer patients undergoing colorectal resection: a randomized control trial. Acta Oncol (Madr) 57:849–859
30. Carli F Bousquet-Dion G Awasthi R Elsherbini N Liberman S Boutros M Effect of multimodal prehabilitation vs postoperative rehabilitation on 30-day postoperative complications for frail patients undergoing resection of colorectal cancer JAMA Surg 2020 155 233 10.1001/jamasurg.2019.5474 31968063
Carli F, Bousquet-Dion G, Awasthi R, Elsherbini N, Liberman S, Boutros M et al (2020) Effect of multimodal prehabilitation vs postoperative rehabilitation on 30-day postoperative complications for frail patients undergoing resection of colorectal cancer. JAMA Surg 155:23331968063
31. Ferreira V Lawson C Carli F Scheede-Bergdahl C Chevalier S Feasibility of a novel mixed-nutrient supplement in a multimodal prehabilitation intervention for lung cancer patients awaiting surgery: a randomized controlled pilot trial Int J Surg 2021 93 106079 10.1016/j.ijsu.2021.106079 34464752
Ferreira V, Lawson C, Carli F, Scheede-Bergdahl C, Chevalier S (2021) Feasibility of a novel mixed-nutrient supplement in a multimodal prehabilitation intervention for lung cancer patients awaiting surgery: a randomized controlled pilot trial. Int J Surg 93:10607934464752
32. Ferreira V Minnella EM Awasthi R Gamsa A Ferri L Mulder D Multimodal Prehabilitation for Lung Cancer Surgery: A Randomized Controlled Trial Ann Thorac Surg 2021 112 1600 1608 10.1016/j.athoracsur.2020.11.022 33321089
Ferreira V, Minnella EM, Awasthi R, Gamsa A, Ferri L, Mulder D et al (2021) Multimodal Prehabilitation for Lung Cancer Surgery: A Randomized Controlled Trial. Ann Thorac Surg 112:1600–160833321089
33. Gillis C Li C Lee L Awasthi R Augustin B Gamsa A Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer Anesthesiology 2014 121 937 947 10.1097/ALN.0000000000000393 25076007
Gillis C, Li C, Lee L, Awasthi R, Augustin B, Gamsa A et al (2014) Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer. Anesthesiology 121:937–94725076007
34. Liu Z Qiu T Pei L Zhang Y Xu L Cui Y Two-week multimodal prehabilitation program improves perioperative functional capability in patients undergoing thoracoscopic lobectomy for lung cancer: a randomized controlled trial Anesth Analg 2020 131 840 849 10.1213/ANE.0000000000004342 31348053
Liu Z, Qiu T, Pei L, Zhang Y, Xu L, Cui Y et al (2020) Two-week multimodal prehabilitation program improves perioperative functional capability in patients undergoing thoracoscopic lobectomy for lung cancer: a randomized controlled trial. Anesth Analg 131:840–84931348053
35. Molenaar CJL Minnella EM Coca-Martinez M ten Cate DWG Regis M Awasthi R Effect of multimodal prehabilitation on reducing postoperative complications and enhancing functional capacity following colorectal cancer surgery JAMA Surg 2023 158 572 10.1001/jamasurg.2023.0198 36988937
Molenaar CJL, Minnella EM, Coca-Martinez M, ten Cate DWG, Regis M, Awasthi R et al (2023) Effect of multimodal prehabilitation on reducing postoperative complications and enhancing functional capacity following colorectal cancer surgery. JAMA Surg 158:57236988937
36. Santa Mina D Hilton WJ Matthew AG Awasthi R Bousquet-Dion G Alibhai SMH Prehabilitation for radical prostatectomy: a multicentre randomized controlled trial Surg Oncol 2018 27 289 298 10.1016/j.suronc.2018.05.010 29937184
Santa Mina D, Hilton WJ, Matthew AG, Awasthi R, Bousquet-Dion G, Alibhai SMH et al (2018) Prehabilitation for radical prostatectomy: a multicentre randomized controlled trial. Surg Oncol 27:289–29829937184
37. Sebio García R Yáñez-Brage MI Giménez Moolhuyzen E Salorio Riobo M Lista Paz A Borro Mate JM Preoperative exercise training prevents functional decline after lung resection surgery: a randomized, single-blind controlled trial Clin Rehabil 2017 31 1057 1067 10.1177/0269215516684179 28730888
Sebio García R, Yáñez-Brage MI, Giménez Moolhuyzen E, Salorio Riobo M, Lista Paz A, Borro Mate JM (2017) Preoperative exercise training prevents functional decline after lung resection surgery: a randomized, single-blind controlled trial. Clin Rehabil 31:1057–106728730888
38. Steffens D Young J Beckenkamp PR Ratcliffe J Rubie F Ansari N Feasibility and acceptability of a preoperative exercise program for patients undergoing major cancer surgery: results from a pilot randomized controlled trial Pilot Feasibility Stud 2021 7 27 10.1186/s40814-021-00765-8 33441181
Steffens D, Young J, Beckenkamp PR, Ratcliffe J, Rubie F, Ansari N et al (2021) Feasibility and acceptability of a preoperative exercise program for patients undergoing major cancer surgery: results from a pilot randomized controlled trial. Pilot Feasibility Stud 7:2733441181
39. Waller E Sutton P Rahman S Allen J Saxton J Aziz O Prehabilitation with wearables versus standard of care before major abdominal cancer surgery: a randomised controlled pilot study (trial registration: NCT04047524) Surg Endosc 2022 36 1008 1017 10.1007/s00464-021-08365-6 33723969
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 36:1008–101733723969
40. Allen SK Brown V White D King D Hunt J Wainwright J Multimodal prehabilitation during neoadjuvant therapy prior to esophagogastric cancer resection: effect on cardiopulmonary exercise test performance, muscle mass and quality of life—a pilot randomized clinical trial Ann Surg Oncol 2022 29 1839 1850 10.1245/s10434-021-11002-0 34725764
Allen SK, Brown V, White D, King D, Hunt J, Wainwright J et al (2022) Multimodal prehabilitation during neoadjuvant therapy prior to esophagogastric cancer resection: effect on cardiopulmonary exercise test performance, muscle mass and quality of life—a pilot randomized clinical trial. Ann Surg Oncol 29:1839–185034725764
41. Banerjee S, Manley K, Shaw B et al (2017) Vigorous intensity aerobic interval exercise in bladder cancer patients prior to radical cystectomy: a feasibility randomised controlled trial. Support Care Cancer. 10.1007/s00520-017-3991-2
42. Dunne DFJ Jack S Jones RP Jones L Lythgoe DT Malik HZ Randomized clinical trial of prehabilitation before planned liver resection Br J Surg 2016 103 504 512 10.1002/bjs.10096 26864728
Dunne DFJ, Jack S, Jones RP, Jones L, Lythgoe DT, Malik HZ et al (2016) Randomized clinical trial of prehabilitation before planned liver resection. Br J Surg 103:504–51226864728
43. Karenovics W Licker M Ellenberger C Christodoulou M Diaper J Bhatia C Short-term preoperative exercise therapy does not improve long-term outcome after lung cancer surgery: a randomized controlled study† Eur J Cardiothorac Surg 2017 52 47 54 10.1093/ejcts/ezx030 28419206
Karenovics W, Licker M, Ellenberger C, Christodoulou M, Diaper J, Bhatia C et al (2017) Short-term preoperative exercise therapy does not improve long-term outcome after lung cancer surgery: a randomized controlled study†. Eur J Cardiothorac Surg 52:47–5428419206
44. Lai Y Su J Qiu P Wang M Zhou K Tang Y Systematic short-term pulmonary rehabilitation before lung cancer lobectomy: a randomized trial Interact Cardiovasc Thorac Surg 2017 25 476 483 10.1093/icvts/ivx141 28520962
Lai Y, Su J, Qiu P, Wang M, Zhou K, Tang Y et al (2017) Systematic short-term pulmonary rehabilitation before lung cancer lobectomy: a randomized trial. Interact Cardiovasc Thorac Surg 25:476–48328520962
45. Ma R-C Zhao Y Liu X Cao H-P Wang Y-Q Yin Y-Y Multimodal exercise program: a pilot randomized trial for patients with lung cancer receiving surgical treatment Clin J Oncol Nurs 2021 25 E26 34 10.1188/21.CJON.E26-E34 34019026
Ma R-C, Zhao Y, Liu X, Cao H-P, Wang Y-Q, Yin Y-Y et al (2021) Multimodal exercise program: a pilot randomized trial for patients with lung cancer receiving surgical treatment. Clin J Oncol Nurs 25:E26-3434019026
46. Morano MT Araújo AS Nascimento FB da Silva GF Mesquita R Pinto JS Preoperative pulmonary rehabilitation versus chest physical therapy in patients undergoing lung cancer resection: a pilot randomized controlled trial Arch Phys Med Rehabil 2013 94 53 58 10.1016/j.apmr.2012.08.206 22926460
Morano MT, Araújo AS, Nascimento FB, da Silva GF, Mesquita R, Pinto JS et al (2013) Preoperative pulmonary rehabilitation versus chest physical therapy in patients undergoing lung cancer resection: a pilot randomized controlled trial. Arch Phys Med Rehabil 94:53–5822926460
47. Moug SJ Mutrie N Barry SJE Mackay G Steele RJC Boachie C Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration: results from the REx trial Colorectal Dis 2019 21 548 562 10.1111/codi.14560 30657249
Moug SJ, Mutrie N, Barry SJE, Mackay G, Steele RJC, Boachie C et al (2019) Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration: results from the REx trial. Colorectal Dis 21:548–56230657249
48. Barberan-Garcia A Ubré M Roca J Lacy AM Burgos F Risco R Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery Ann Surg 2018 267 50 56 10.1097/SLA.0000000000002293 28489682
Barberan-Garcia A, Ubré M, Roca J, Lacy AM, Burgos F, Risco R et al (2018) Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery. Ann Surg 267:50–5628489682
49. Bausys A Luksta M Anglickiene G Maneikiene VV Kryzauskas M Rybakovas A Effect of home-based prehabilitation on postoperative complications after surgery for gastric cancer: randomized clinical trial Br J Surg 2023 110 1800 10.1093/bjs/znad312 37750588
Bausys A, Luksta M, Anglickiene G, Maneikiene VV, Kryzauskas M, Rybakovas A et al (2023) Effect of home-based prehabilitation on postoperative complications after surgery for gastric cancer: randomized clinical trial. Br J Surg 110:180037750588
50. Karlsson E Farahnak P Franzén E Nygren-Bonnier M Dronkers J van Meeteren N Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery – a randomized controlled design PLoS ONE 2019 14 e0219158 10.1371/journal.pone.0219158 31265476
Karlsson E, Farahnak P, Franzén E, Nygren-Bonnier M, Dronkers J, van Meeteren N et al (2019) Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery – a randomized controlled design. PLoS ONE 14:e021915831265476
51. Higgins JPT Altman DG Gotzsche PC Juni P Moher D Oxman AD The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials BMJ 2011 343 d5928 d5928 10.1136/bmj.d5928 22008217
Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928–d592822008217
52. Fiuza-Luces C Valenzuela PL Gálvez BG Ramírez M López-Soto A Simpson RJ The effect of physical exercise on anticancer immunity Nat Rev Immunol. 2023 24 282 10.1038/s41577-023-00943-0 37794239
Fiuza-Luces C, Valenzuela PL, Gálvez BG, Ramírez M, López-Soto A, Simpson RJ et al (2023) The effect of physical exercise on anticancer immunity. Nat Rev Immunol. 24:28237794239
53. Fiuza-Luces C Valenzuela PL Santos-Lozano A Ruiz-Casado A Lucia A Exercise and quality of life in cancer J Sport Health Sci 2023 12 489 490 10.1016/j.jshs.2023.01.001 36621566
Fiuza-Luces C, Valenzuela PL, Santos-Lozano A, Ruiz-Casado A, Lucia A (2023) Exercise and quality of life in cancer. J Sport Health Sci 12:489–49036621566
54. Ruiz-Casado A Martín-Ruiz A Pérez LM Provencio M Fiuza-Luces C Lucia A Exercise and the hallmarks of cancer Trends Cancer 2017 3 423 441 10.1016/j.trecan.2017.04.007 28718417
Ruiz-Casado A, Martín-Ruiz A, Pérez LM, Provencio M, Fiuza-Luces C, Lucia A (2017) Exercise and the hallmarks of cancer. Trends Cancer 3:423–44128718417
55. Laza-Cagigas R, Seijo M, Swaine I, Rampal T, Naclerio F (2024) Commentary: key aspects of multimodal prehabilitation in surgical patients with cancer. A practical approach to integrating resistance exercise programmes. Eval Health Prof 47(3):336–342. 10.1177/01632787231218993
