Prehabilitation for Colon Cancer Surgery: A Systematic Review of Quality-of-Life Outcomes and a Feasibility Study

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Stadelhofer, Helene R. Dalby, Anne V. Thyø, Katrine J. Emmertsen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9451596/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Purpose To evaluate the feasibility of short-term prehabilitation and its impact on quality of life in patients with colorectal cancer through a systematic review and a feasibility study. Methods The systematic review was conducted in accordance with the PRISMA guidelines. PubMed, PubPsych, CINAHL, EMBASE, Web of Science and EBSCOhost were searched for studies evaluating quality of life in colorectal cancer patients undergoing prehabilitation. We conducted a prospective non-randomised interventional feasibility study, with a two-week post-surgery follow-up, enrolling patients diagnosed with colon cancer. Results The systematic review included six studies from 517 unique records for final analysis. Among six studies, evidence for quality-of-life benefits of prehabilitation was conflicting but predominantly favourable, with generally low-to-moderate study quality and substantial heterogeneity. In the feasibility study 110 patients were eligible for inclusion; 70 (64%) were included, and 63 completed the entire study. Of the 32 patients in the intervention group, compliance > 80% was observed in 66% (nutrition) and 88% (physical activity) of patients, with a median compliance of 100% for both. Quality-of-life outcomes were explored as secondary measures and showed favourable trends following prehabilitation. Conclusion Evidence on the effect of prehabilitation on quality of life in colorectal cancer remains inconsistent; Our feasibility study shows that short-term multimodal prehabilitation is feasible and supports the need for adequately powered trials. Colorectal-cancer Prehabilitation Feasibility Systematic review Quality of Life (QoL) PROMS Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Colorectal cancer is the third most common cancer worldwide [ 1 ], and surgical resection remains the only curative treatment [ 2 ]. Although advances in minimally invasive techniques have improved short-term postoperative outcomes [ 3 ], particularly older and frail patients can experience functional decline and reduced quality of life (QoL) following surgery [ 4 – 6 ]. Surgery triggers a cascade of stress-mediated responses in the body, including hypermetabolism, hypercatabolism and inflammation, which impair immune function and wound healing [ 7 ]. A prolonged disease course and postoperative complications are associated with an increased risk of worse long-term outcomes and poorer long-term QoL [ 8 ]. Prehabilitation can be a proactive approach to optimise the patients’ physical function, nutritional status, and mental health before surgery, thereby improving post-operative recovery and outcomes [ 9 – 11 ]. Although prehabilitation may delay surgical treatment, it enables patients to remain actively engaged during the waiting period, fostering a greater sense of inclusion. Despite increasing awareness and research on prehabilitation [ 10 – 12 ], substantial gaps remain regarding its effects on post-surgical recovery, QoL, and compliance. This study aimed to evaluate prehabilitation for patients with colon cancer, with a specific focus on QoL. The evaluation was performed in two ways: first, a systematic review was conducted to identify how QoL has been measured and reported in existing literature. Second, a feasibility study was conducted to evaluate the practicality and short-term outcomes of a multimodal prehabilitation programme within a clinical setting. Methods A systematic review was conducted to provide context, identify evidence gaps, and inform the modification and interpretation of the feasibility study findings. Systematic review A comprehensive literature search was performed in the following databases: PubMed, PubPsych, CINAHL, EMBASE, Web of Science and EBSCOhost. Peer-reviewed studies evaluating the effect of prehabilitation on QoL in patients ≥ 18 years of age undergoing surgery for colorectal cancer were included. Case reports, case series, letters, and editorials were excluded. No language restriction was employed. A translation system was applied if a study was available only in a foreign language. The systematic review was conducted and reported according to the PRISMA guidelines [ 13 , 14 ]. The study protocol was registered at Aarhus University, though not publicly available. The searches were performed on the 28th of August 2023 and updated on the 17th of October 2024, in accordance with the AMSTAR guidelines [ 15 ]. Searches span from the earliest available records to the search date. Supplement 1 elaborates on the search string and on the results from the first and second searches. Study selection and extraction After duplicate removal, titles, abstracts and full texts were screened by two independent authors (M.S. and A.T.) using the management software Covidence. Studies identified from conference abstracts or review citations were screened for full text. Any disagreements were resolved by discussion. If consensus could not be reached, the last author made the final decision. The first author (M.S.) performed data extraction and quality assessment. For quality assessment, a tool specific to each study design was used in accordance with clinical guidelines. For randomised controlled trials (RCTs), the Cochrane-recommended risk-of-bias tool for randomised trials, version 2 (RoB2), was applied [ 16 ]. For cohort studies, the Newcastle-Ottawa scale (NOS) quality assessment form was used [ 17 ]. The RoB2 tool evaluates risk of bias across five main domains: 1. the randomisation process, 2. deviations from intended intervention, 3. missing data, 4. outcome measurement, and 5. selection of results. Each domain was judged to have low risk, some concerns, or high risk of bias, with an overall judgement derived from the domain-level assessment. The NOS comprises eight items distributed across three domains - Selection, Comparability, and Outcome, each awarded stars for quality. To facilitate comparability across study designs, NOS scores of good, fair, or poor quality were converted to the Agency for Healthcare Research and Quality (AHRQ) standards using previously established thresholds [ 18 ]. Studies were classified as good quality when they achieved high scores across all domains (≥ 3 in Selection, ≥ 1 in Comparability, ≥ 2 in Outcome). Fair quality corresponded to moderate scores (2/≥1/≥2), whereas poor quality reflected low performance in any domain (≤ 1/0/≤1). Feasibility study This was a non-randomised interventional feasibility study conducted in the Surgical Department, Regional Hospital Randers, Denmark. All patients diagnosed with colon cancer were prospectively enrolled after being screened for eligibility from September 2022 to June 2023. Inclusion criteria were age ≥ 18 years and endoscopic macroscopically malignant tumour, later confirmed by pathological examination. Patients were excluded if they were ineligible for the intended curative colonic resection or unable to complete questionnaires due to language or cognitive impairment. Eligible patients were enrolled by a care coordinator on the day of cancer-suspect findings during colonoscopy or within two days by phone. The first author or a specialised care coordinator carried out enrolments. Consent was obtained from all participants after they received oral and written information about the study. Patients diagnosed at Regional Hospital Randers were assigned to the intervention group, whereas patients referred to the hospital after a colonoscopy at another hospital or private clinic comprised the non-intervention group. All patients were approached and enrolled within three days of the diagnostic colonoscopy. Intervention and non-intervention groups The intervention group received education on the effects of nutrition and exercise on post-surgical recovery, a prescription for nutritional drinks, and a pamphlet containing recipes for homemade supplements. They were encouraged to perform at least 20 minutes of moderate daily exercise (e.g. walking, aerobic training, stretching, or other preferred cardio activities) and to ingest three nutritional drinks (200 mL ∼ 300 Kcal per drink) every day until surgery. If patients had conditions requiring special dietary attention (e.g., diabetes or kidney disease), a dietitian was consulted. The non-intervention group received standard care, including advice on protein-rich nutrition and exercise, until surgery, but without specific guidelines. All patients underwent standard diagnostic evaluation, including CT imaging and histopathological confirmation of the cancer diagnosis, followed by an individual care discussion at a local multidisciplinary team meeting. Patients were subsequently seen in the surgical outpatient clinic for treatment planning and offered surgery within 10 days in accordance with Danish healthcare regulations. Outcomes and measures A timeline for outcome assessments is shown in Fig. 1 . All patients completed a structured interview at inclusion and at follow-up, approximately 2 weeks post-surgery. The interview included patient-reported outcome measures (PROMs) assessing QoL and compliance with the intervention. The PROMs and additional questions were pilot tested in a focus group to ensure quality and comprehensibility. The final versions are available in Supplementary 2. Primary outcome The primary outcome was intervention compliance, assessed through patient self-reporting at follow-up. Participants recorded the number of days they adhered to the prescribed intervention. Compliance was defined as the extent to which patients adhered to the intervention instructions. A percentage score was subsequently calculated in accordance with the proportion of intake of nutritional drinks: \(\:\frac{Number\:of\:consumed\:nutritional\:drinks}{Optimal\:number\:of\:nutritional\:drinks}*100\%\) . The same methodology was applied to assess physical activity. There is currently no validated gold standard for defining an acceptable adherence threshold in prehabilitation research. Historically, an arbitrary rate of 80% or higher has been considered good compliance [ 19 , 20 ]. Additional outcomes Secondary outcomes included both clinical and patient-reported measures (PROMS). Clinical data extracted from medical records comprised weight change during the study period, length of hospital stay (LOS), and surgical and medical complications. Complications were categorised by severity using the Clavien-Dindo classification system, ranging from grade 0 (no complication) to grade 5 (death) [ 21 ]. Weight was measured at baseline and on the day of surgery. PROMs included ad hoc questions exploring patients’ sense of inclusion within the disease course and self-reported cancer-related symptoms, as well as validated instruments assessing quality of recovery (QoR) by Quality of Recovery-15 (QOR-15) [ 22 ] and QoL using the EuroQol (EQ)-5D-5L and EQ visual analogue scale (VAS) [ 23 , 24 ]. All instruments have previously been validated in a Danish cohort [ 24 – 26 ]. The QOR-15 encompasses 15 domains related to post-surgery daily activities and symptoms. Scores range from 0 to 150, with higher scores indicating better post-surgery recovery. The EuroQol (EQ)-5D-5L [ 23 , 24 ] evaluates five domains (mobility, personal hygiene, usual activities, pain, and anxiety/depression) on five levels, reflecting the patients’ perception of their health status, while the VAS score evaluated the patients’ self-rated health on a visual scale ranging from 0 to 100, where 100 is labelled “the best health you can imagine” and 0 “the worst health you can imagine”. The EQ-5D-5L and VAS scores were measured at both baseline and follow-up. Evaluation of patients’ feelings of inclusion was incorporated in the post-surgery questionnaire. Patients were asked to what degree they felt they had a role in their disease course. Five degrees were presented, ranging from "not at all" to "a very high degree". Self-reported cancer symptoms were assessed at baseline. Patients were asked about unintentional weight loss in the previous six months and reduced appetite or fatigue in the past 2 weeks. Follow-up assessment Follow-up was scheduled at the patients’ routine clinic appointment 13–15 days post-surgery, when they were seen for a postoperative check-up and received their final histopathology results of the colon resection (Fig. 1 ). The first author administered the follow-up questionnaire immediately before the appointment with the surgeon to minimise bias related to prognosis and subsequent treatment decisions. Statistical analysis Data analyses were performed in R (2023). Descriptive statistics were compiled to characterise the study population, with quantitative data summarised as medians with interquartile range (IQR), and categorical variables summarised as counts and percentages. As a feasibility study, data analysis was primarily descriptive and exploratory. Group differences in categorical variables were assessed using Fisher’s exact test or Pearson’s Chi-squared test, as appropriate. Continuous variables were compared using t-tests for parametric data and the Wilcoxon rank-sum test for non-parametric data. All analyses were exploratory, as the study was not powered to detect statistically significant differences. Any statistically significant findings should therefore be interpreted with caution, as highlighted in the discussion session. Results Systematic review The primary literature search identified 633 records. After removing duplicates, 517 unique records were screened. The PRISMA flowchart is illustrated in Fig. 2. Studies were primarily excluded because QoL was not measured. A total of six studies were included in the final analysis [27–32]. The updated literature search yielded no records for inclusion. Study characteristics are presented in Table 1, including the number of participants included, the composition of the interventions, and the quality assessment. Only the cohort study by Li et al. (2012) [31] was assessed as good quality. Two studies [30, 32] received an overall assessment of poor quality, primarily due to a high number of participants lost to follow-up or missing data. The remaining three studies were evaluated as of moderate/fair quality [27–29]. Characteristics of the prehabilitation programs The included studies varied substantially in their prehabilitation interventions with respect to modality (uni-, multi-, or trimodal), duration, and specific intervention characteristics, such as the intensity of physical activity (Table 1). Four studies [27, 29–31] analysed QoL scores comparing a rehabilitation group with a control group. In general, the studies reported high levels of compliance with the prehabilitation program. (Suggesting table 1 here ( attached as a separate file, due to page rotation) Quality of life outcomes None of the included studies measured QoL as a primary outcome; it was measured only as a secondary or additional outcome. The studies primarily employed the 36-Item Short-Form Health Survey (SF-36). Table 1 provides further details on outcome measures. Due to heterogeneity across studies, particularly in the intervention programs, a meta-analysis could not be performed. Instead, studies have been systematically compared. A detailed illustration of the available data for QoL outcomes is shown in Table 2. Four studies [28–30, 32] reported that prehabilitation had a positive effect on QoL, while two studies [27, 31] found no improvement. One study [29] reported a statistically significant improvement in the prehabilitation group compared to the control group at seven days post-surgery, whereas two studies [27] , [31] found no significant differences between the prehabilitation group and the comparison group. Feasibility study Missing participants mainly refers to cases where contact could not be established or where patients were not offered the opportunity to participate in time. Of the 110 eligible patients, 70 (64%) were included in the study. Of these 63 patients (90%), completed the follow-up (Fig. 3). No significant differences in age or gender were observed between included and excluded patients. Similarly, analysis of dropouts and patients excluded after baseline revealed no differences in baseline characteristics. Baseline characteristics and operative characteristics are shown in Table 3. Overall, no significant differences in baseline characteristics were observed between the two groups. The interval between the initial endoscopy and the surgery date was 2–3 weeks. Compliance with the prehabilitation intervention After inclusion, seven (10%) patients withdrew from the study. Among patients who completed the study, the mean compliance score for the nutritional intervention was 80% (IQR 65–100), and for the physical activity intervention, 89% (IQR 71–100). A nutritional component compliance score exceeding 80% was achieved by 66% of all patients, with a median compliance value of 100%. Compliance was slightly higher for the physical activity component, with 88% of all patients scoring above 80%, and a median compliance of 100%. Feeling of inclusion in one's own course of the disease In the intervention group, 38% of patients reported not feeling included, compared with 70% in the non-intervention group. In the intervention group, the majority reported feeling included to a very high (9%), high (16%), or moderate degree (28%), whereas only a minority reported feeling included to a low degree (9%). In contrast, the non-intervention group showed a markedly different distribution, with only one (3%) reporting a very high degree of feeling included, and fewer patients indicating high (10%), moderate (10%), and low (7%) degrees of inclusion. Quality of life - the EQ-5D-5L Figure 4 shows the distribution of EQ-5D-5L responses at baseline and follow-up (post-surgery) for the intervention and non-intervention groups. At baseline, domain profiles were broadly comparable. Except for anxiety and depression, both groups demonstrated a decline across all severity types from baseline to the post-surgical period. Post-surgery, several notable trends emerged. For usual activities, the non-intervention group demonstrated a marked shift towards moderate-to-severe problems. In contrast, the intervention group retained a higher proportion in the no or only slight problems categories. As for anxiety/depression, the intervention group generally reported a more favourable distribution with a lesser degree of problems compared to the non-intervention group. The intervention group also reported fewer moderate-severe problems than the non-intervention group. The proportion of patients reporting pain/discomfort was comparable post-surgery, although patients in the non-intervention group reported pain/discomfort more frequently at baseline. Post-surgery EQ-VAS scores differed significantly between groups (p = 0.047). Scores increased slightly from baseline to post-surgery in the intervention group (from a median of 77.0 to 79.0), whereas they declined in the non-intervention group (from a median of 70.0 to 65.0). Additional outcomes : At baseline, patients exhibited a wide range of cancer-related symptoms. Approximately 33% had experienced unintended moderate weight loss and reported a reduced appetite compared to normal. More than half reported some degree of fatigue, and 25% presented with anaemia at diagnosis. From baseline to surgery, weight change was small overall, with a median gain of 0.45 kg (IQR: -0.70-1.53). Most patients maintained a relatively stable weight during the preoperative period and did not experience further weight loss. Weight data on the day of surgery were missing for 15 patients (9 in the intervention group and 6 in the non-intervention group). For these patients, weight was obtained on the first or second postoperative day. Only five patients had no post-surgery weight data available. During hospitalisation, patients in the two groups showed similar patterns. Patients in the intervention group had a median LOS of 3.5 days (IQR 3.0-8.3), and those in the non-intervention group had a median LOS of 4.0 days (IQR 3.0–5.0). Generally, the number of perioperative and post-surgical complications was low and evenly distributed between the two groups, as was the case when converted to the Clavien-Dindo classification. The most common post-surgery complications were paralytic ileus, incisional hernia, and anastomotic leakages, with three patients experiencing each outcome. Anastomotic leakage was observed in two patients in the intervention group and in one in the non-intervention group. The QoR scores were similar between groups, with similar medians and overlapping interquartile ranges. The non-intervention group exhibited a wider score distribution and more low-value outliers, whereas the intervention group showed a more clustered score profile (data now shown). Discussion This systematic review updates the evidence of the effect of prehabilitation on QoL in patients undergoing surgery for colorectal cancer. Although the included studies reported heterogeneous findings, most suggested potential improvements in QoL associated with prehabilitation, with only one demonstrating a statistically significant benefit compared to controls. The feasibility study primarily evaluated compliance with a short-term multimodal prehabilitation programme in patients undergoing surgery for colonic cancer. Overall compliance was high, with 66% of participants achieving > 80% compliance with the nutritional component and 88% with the physical activity component. This demonstrates that prehabilitation is feasible in this clinical setting without compromising the planned surgical treatment. Since this clinical trial was designed as a feasibility study, the secondary outcomes were not intended to support causal inferences and should not be interpreted as evidence of prehabilitation effects. Nevertheless, they provide insights into potential patterns. Consistent with the systematic review, QoL outcomes showed favourable trends following prehabilitation, particularly in domains of returning to usual activities and reducing anxiety and depression, although none reached statistical significance. A modest statistically significant improvement in self-perceived general health was observed at 2 weeks post-surgery. However, this cannot be interpreted as a valid significance test given the relatively small sample size and the study's limited power. The findings regarding global QoL are consistent with prior cancer-specific trials and reviews, suggesting less consistent effects on global QoL scores. Earlier studies [ 12 , 33 , 34 ] more often reported no change or a decline in QoL scores, whereas more recent studies consistently report a relatively small but positive effect of prehabilitation on QoL or differences between groups [ 35 , 36 ]. A systematic review [ 37 ] and a Cochrane review [ 38 ] focusing exclusively on colorectal cancer have recently been published. However, as these reviews included only RCTs, they were unable to analyse QoL outcomes due to the limited number of eligible studies. To our knowledge, the present review is the first to specifically focus on prehabilitation for colorectal cancer and QoL outcomes across both RCTs and observational studies. The inclusion of diverse study designs inevitably introduced heterogeneity among the included studies, further compounded by variation in prehabilitation modalities, intervention duration, and outcome measures. Similar challenges have been reported in other reviews in this field, including that by Chou et al. [ 39 ]. Our systematic review found that only one study [ 31 ] had a low risk of bias, while the rest were rated as fair to poor quality. A key methodological limitation across several studies was the small number of patients undergoing prehabilitation. In addition, the assessment of QoL represented a recurring methodological concern, reflecting heterogeneity in measurement instruments and reporting. Despite the use of validated questionnaires across studies, the assessment of QoL remains subjective and may be influenced by recall or timing-related bias. The generally low methodological quality of studies evaluating QoL outcomes could partly reflect that QoL is often considered as a secondary endpoint and assessed over relatively short follow-up periods. In addition, differences in outcome definitions, subdomains, and measurement instruments limit comparability across and reduce the feasibility of pooled analyses. International variation in prehabilitation practices poses challenges for standardising. Programmes differ in duration, modality, target population, and intervention intensity, complicating comparisons between interventions and their effects. The optimal timing for colorectal cancer surgery has been discussed in the literature, with suggestions ranging from 2–6 weeks [ 40 ]. In Denmark, the maximum waiting period from final diagnosis of colorectal cancer to surgery is 10 days. However, under recent Danish legislation, surgeons are allowed to postpone surgery to prescribe prehabilitation if deemed necessary to optimise the patient before surgery [ 41 ]. This feasibility study provides valuable insight, showing that even a brief prehabilitation intervention can achieve high compliance, particularly for the nutritional and physical activity components. This is clinically relevant, as the limited time between diagnosis and surgery is frequently cited as a key barrier to implementing prehabilitation [ 42 ]. Compared with the existing literature, several prehabilitation studies across various cancer types have demonstrated similar compliance rates of 70–80% or higher [ 11 , 43 , 44 ]. This trend was also observed in several multimodal studies included in our systematic review [ 27 , 28 , 31 ]. Consistent with our findings, several studies have found that compliance with physical activity interventions tends to be higher than with nutritional interventions. The very high compliance observed with the physical activity intervention is likely due to its simple, flexible nature, which allows for individual patient interpretation. From a clinical perspective, these combined findings support the feasibility of incorporating a short-term multimodal prehabilitation into colorectal cancer treatment pathways. We acknowledge that in a trial setting, additional resources may be available, which may contribute to higher patient compliance. Nevertheless, we observed trends toward greater patient involvement in their disease course, suggesting that prehabilitation may promote higher compliance and potential benefits by enhancing patient engagement, empowerment, and preparedness. Strengths and limitations The main strength of this work is the integration of a systematic synthesis of evidence with original feasibility data, enabling combined interpretations. The systematic review followed PRISMA guidelines, and searches were developed in collaboration with a librarian and employed a clearly defined search strategy across a comprehensive range of databases without language restrictions. Reference lists were screened, and appropriate quality assessment tools were carefully selected to suit each specific study design. A key strength of the feasibility study is the low drop-out rate (10%). Patients who withdrew did not differ significantly from those who completed the study in terms of age, gender, ASA classification, performance status, or BMI. Another notable strength is the inclusion of patient-centered outcomes that go beyond traditional QoL measures, such as feelings of inclusion and QoR, assessed within a non-randomised controlled design. Although patient involvement in care is increasingly recognised as a crucial factor for satisfaction and perceived benefit, it remains underreported in prehabilitation research. There are some limitations to our studies. Within the systematic review, the broad inclusion of study designs inevitably introduced heterogeneity among the included studies. Although the search was updated in 2024, publication of the findings was delayed by over a year, and no additional updates were made. The feasibility study was non-randomised and not powered to assess efficacy outcomes, limiting causal inference drawing and reducing generalisability. The small sample size represents an additional limitation. Although the inclusion rate was 64%, legal constraints prevented data collection from non-participants, thereby preventing statistical comparisons. Consequently, selection bias cannot be ruled out. Prehabilitation is considered particularly beneficial for frail patients [ 45 ]. However, such patients are challenging to involve in research. It is possible that some very frail patients were not included in the study, potentially introducing selection bias and affecting internal validity. Although no statistically significant differences in baseline characteristics were observed between the intervention and non-intervention groups, a trend toward higher baseline ASA scores in the non-intervention group should be acknowledged. Finally, compliance scores and PROMS were primarily based on self-reported data and may be subject to recall bias. Future aspects While our prehabilitation intervention is feasible to implement, the future application of prehabilitation on a larger scale faces several challenges, particularly in logistics and resource allocation within a hospital's daily workflow. Previous research in this field suggests that applying a multimodal or trimodal prehabilitation lasting for at least 3 weeks is necessary to achieve full benefits [ 45 ]. To achieve greater consistency, there is a need for consensus on the definitions of prehabilitation, intervention modalities, and the screening tools employed to determine when to implement a prehabilitation program. A recent Delphi study by Fish et al. [ 46 ] proposed a more standardised approach to prehabilitation and may provide guidance for future trials. Greater standardisation could lead to higher-quality and more homogeneous evidence, facilitating evidence synthesis and improving the translation of prehabilitation research into patient benefit. Obstacles also include the lack of qualified staff and restricted financial resources. Moreover, there is a need for studies evaluating the economic impact of prehabilitation in this patient population, even though early prehabilitation interventions may be cost-effective by reducing the burden of postoperative complications. To evaluate the causal effects of prehabilitation on outcomes such as QoL, post-surgery complications, QoR, and patients’ sense of inclusion, more high-quality RCTs with large sample sizes are needed. Although satisfactory compliance was observed, the effectiveness of short-term prehabilitation should be evaluated in longer and more comprehensive programmes. In addition, clearer guidelines are needed on when curative surgery should be postponed in favour of prehabilitation and how best to identify patients most likely to benefit. Conclusion Overall, our findings suggest that, while robust evidence for definitive effects of prehabilitation on QoL remains limited, prehabilitation appears acceptable, implementable, and potentially beneficial from a patient perspective. This supports further evaluation in adequately powered trials with QoL as a primary outcome. The studies included in the review showed substantial heterogeneity and, at times, conflicting results, underscoring the need for additional high-quality research. Our feasibility study further demonstrated favourable trends across PROMs, including QoL-related domains and patients’ perceived feelings of inclusion. Future research should aim to establish consensus-based intervention frameworks, incorporate economic cost-benefit analyses, and develop guidance on optimal timing, duration, and patient selection. Declarations Conflict of interests: None Address correspondence to Michelle Vestergaard Stadelhofer, Aarhus University, Ny Munkegade 120, Building 1521, 1st floor, DK-8000 Aarhus C. [email protected] or [email protected] Fundings: This project was funded by Randers Regional Hospital, the Louis-Hansen fund, the Health Research Foundation of Central Denmark Region, and the Family Hede Nielsen fund. Author Contribution M.V.S., H.R.D, A.V.T, K.J.E, conceptualised and designed the study. M.V.S developed the data-collection instruments, while A.V.T, K.J.E assisted and revised the data-collection instruments. M.V.S and A.V.T conducted data collection. M.V.S carried out the analyses, drafted the initial manuscript, and H.R.D, A.V.T, K.J.E critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Acknowledgement A special thanks to all study participants for making this study possible, and to the coordinating nurses Jytte Würtz, Birgitte Christiansen, and Anne Majholm for their indispensable assistance with patient enrolment and data collection. Sincere thanks also to Thomas Skelde Krøjmand for expert statistical guidance. Data Availability The data supporting the findings of this study are available within the article and its Supplementary Information. 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Nutr Clin Pract 37(3):645–653 Li C et al (2012) Trimodal prehabilitation program improves functional recovery in colorectal cancer surgery: A pilot study. Surg Endoscopy Other Interventional Techniques 26:S243 Minnella EM et al (2016) Patients with poor baseline walking capacity are most likely to improve their functional status with multimodal prehabilitation. Surgery 160(4):1070–1079 Carli F 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(3):233 Luther A et al (2018) The Impact of Total Body Prehabilitation on Post-Operative Outcomes After Major Abdominal Surgery: A Systematic Review. World J Surg 42(9):2781–2791 Loudovici-Krug D et al (2025) Physical Prehabilitation for Older Patients with Cancer before Complex Medical-Surgical Interventions: An Umbrella Review. Aging and disease, : p. 0 Wullaert L et al (2023) Oncological surgery follow-up and quality of life: meta-analysis. Br J Surg 110(6):655–665 Machado P et al (2024) Effect of home-based exercise prehabilitation on postoperative outcomes in colorectal cancer surgery: a systematic review and meta-analysis. Support Care Cancer 33(1):20 Molenaar CJ et al (2023) Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery. Cochrane Database Syst Rev 5(5):CD013259 Chou YJ, Kuo HJ, Shun SC (2018) Cancer Prehabilitation Programs and Their Effects on Quality of Life. Oncol Nurs Forum 45(6):726–736 Hanna TP et al (2020) Mortality due to cancer treatment delay: systematic review and meta-analysis. BMJ, : p. m4087 Sundhedsstyrelsen (2022) Pakkeforløb for kræft i tyk- og endetarm. Sundhedsstyrelsen, Editor Furyk C et al (2021) Prehabilitation for Frail Patients Undergoing Colorectal Surgery: Lessons Learnt From a Randomised Feasibility Study. Front Rehabilitation Sci, 2 Jensen BT et al (2019) Implementing a Multimodal Prehabilitation Program to Radical Cystectomy in a Comprehensive Cancer Center: A Pilot Study to Assess Feasibility and Outcomes. Urol Nurs 39(6):303–313 Karlsson E et al (2019) Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery – A randomized controlled design. PLoS ONE 14(7):e0219158 Molenaar CJL et al (2023) Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery. JAMA Surg 158(6):572 Fish R et al (2024) Defining standards and core outcomes for clinical trials in prehabilitation for colorectal surgery (DiSCO): modified Delphi methodology to achieve patient and healthcare professional consensus. BJS, 111(6) Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.pdf Table3.pdf Table2.pdf Appendix1.pdf Appendix2english.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 14 May, 2026 Reviews received at journal 14 May, 2026 Reviews received at journal 12 May, 2026 Reviewers agreed at journal 24 Apr, 2026 Reviewers agreed at journal 24 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers invited by journal 22 Apr, 2026 Editor assigned by journal 21 Apr, 2026 Submission checks completed at journal 21 Apr, 2026 First submitted to journal 17 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9451596","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":629237351,"identity":"3223d083-2025-45d4-a783-ed3720a4beca","order_by":0,"name":"Michelle V. Stadelhofer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYDACZhDBZsPAxwzhM84gQgtjAwNbGgMb8VoYwFoOM7DBeAS16LazP3/wo+y8PBs77wGGn20MsjMbCGgxO8xj2Nhz7rZhGzNfAmNvG4PxbEK2ALUwNvC23U5gY+YxYOBtY0icR1gL+8PGv23nwFoY/xKnhcGwmbftAFgLM8gWYhxmOFvmXDLQLzwGh2XOSRgT9v754w8+vimzk+fnP2P48E2ZjeyMA4SsQQZAxRKkqB8Fo2AUjIJRgAsAAIuIOHMqO07hAAAAAElFTkSuQmCC","orcid":"","institution":"Randers Regional Hospital","correspondingAuthor":true,"prefix":"","firstName":"Michelle","middleName":"V.","lastName":"Stadelhofer","suffix":""},{"id":629237352,"identity":"a5da4745-e574-4f2e-b242-bdef4968947a","order_by":1,"name":"Helene R. Dalby","email":"","orcid":"","institution":"Randers Regional Hospital","correspondingAuthor":false,"prefix":"","firstName":"Helene","middleName":"R.","lastName":"Dalby","suffix":""},{"id":629237353,"identity":"7e1d231b-d41f-43cb-9b6a-815da6f75446","order_by":2,"name":"Anne V. Thyø","email":"","orcid":"","institution":"Randers Regional Hospital","correspondingAuthor":false,"prefix":"","firstName":"Anne","middleName":"V.","lastName":"Thyø","suffix":""},{"id":629237354,"identity":"8d6be590-e56e-4720-9343-ba0b11f2322b","order_by":3,"name":"Katrine J. Emmertsen","email":"","orcid":"","institution":"Randers Regional Hospital","correspondingAuthor":false,"prefix":"","firstName":"Katrine","middleName":"J.","lastName":"Emmertsen","suffix":""}],"badges":[],"createdAt":"2026-04-17 17:09:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9451596/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9451596/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108492474,"identity":"c3e63a0c-c041-48fe-853b-0d03d663b186","added_by":"auto","created_at":"2026-05-05 09:57:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":122862,"visible":true,"origin":"","legend":"\u003cp\u003eStudy timeline and timepoints of data assessments.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/9ef9e30aa6cf63793de47164.png"},{"id":108409211,"identity":"0023ea95-461d-4df5-970b-1d6f46c9f32f","added_by":"auto","created_at":"2026-05-04 09:59:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":82827,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flowchart of the screening process.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/64f0a729788992eca059781c.png"},{"id":108409212,"identity":"f5ea000e-0fa0-4447-8a02-a2363e5db0b1","added_by":"auto","created_at":"2026-05-04 09:59:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":61140,"visible":true,"origin":"","legend":"\u003cp\u003eParticipant flow and data completeness.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/3f019ef0ab7cb935449c16d6.png"},{"id":108492475,"identity":"9b6db133-f174-491e-ae24-a9b97800a1cf","added_by":"auto","created_at":"2026-05-05 09:57:50","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":790832,"visible":true,"origin":"","legend":"\u003cp\u003eEQ5D5L at baseline and post-surgery for the intervention and the non-intervention group. Including a box plot of the VAS score of self-reported general health.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/d4b5c675bfa2af0b6fe34dd4.jpeg"},{"id":108494610,"identity":"29d3fce2-0f79-4d49-a2e3-521d93b9eb3e","added_by":"auto","created_at":"2026-05-05 10:05:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1377387,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/ba8ad99c-48ba-4f6a-a1fa-7a710b439b91.pdf"},{"id":108492543,"identity":"efe60a93-806a-419e-a4cd-5176b942107d","added_by":"auto","created_at":"2026-05-05 09:58:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":228569,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/05adc1208d3ac4703d7eb1e7.pdf"},{"id":108409210,"identity":"3a6f0cfd-6452-45f2-a1c0-509677a9b931","added_by":"auto","created_at":"2026-05-04 09:59:05","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":155059,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/8a7c483c94bc79153c3c3ebb.pdf"},{"id":108492605,"identity":"acd238c7-e94d-45c8-9622-b179ce858b14","added_by":"auto","created_at":"2026-05-05 09:58:09","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":202182,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/fab2e40cdacfa24353d603b4.pdf"},{"id":108409214,"identity":"75936637-7b10-46bc-a861-8ac463722849","added_by":"auto","created_at":"2026-05-04 09:59:05","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":180640,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/732d7a01f14dd664d97fa03e.pdf"},{"id":108493119,"identity":"1f893f11-7f62-4cf7-81ce-f1d3662b009c","added_by":"auto","created_at":"2026-05-05 09:59:25","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":364100,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix2english.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9451596/v1/e36004ef56d6cce3086046e8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prehabilitation for Colon Cancer Surgery: A Systematic Review of Quality-of-Life Outcomes and a Feasibility Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer is the third most common cancer worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and surgical resection remains the only curative treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Although advances in minimally invasive techniques have improved short-term postoperative outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], particularly older and frail patients can experience functional decline and reduced quality of life (QoL) following surgery [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Surgery triggers a cascade of stress-mediated responses in the body, including hypermetabolism, hypercatabolism and inflammation, which impair immune function and wound healing [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A prolonged disease course and postoperative complications are associated with an increased risk of worse long-term outcomes and poorer long-term QoL [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Prehabilitation can be a proactive approach to optimise the patients\u0026rsquo; physical function, nutritional status, and mental health before surgery, thereby improving post-operative recovery and outcomes [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Although prehabilitation may delay surgical treatment, it enables patients to remain actively engaged during the waiting period, fostering a greater sense of inclusion.\u003c/p\u003e \u003cp\u003eDespite increasing awareness and research on prehabilitation [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], substantial gaps remain regarding its effects on post-surgical recovery, QoL, and compliance. This study aimed to evaluate prehabilitation for patients with colon cancer, with a specific focus on QoL.\u003c/p\u003e \u003cp\u003eThe evaluation was performed in two ways: first, a systematic review was conducted to identify how QoL has been measured and reported in existing literature. Second, a feasibility study was conducted to evaluate the practicality and short-term outcomes of a multimodal prehabilitation programme within a clinical setting.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA systematic review was conducted to provide context, identify evidence gaps, and inform the modification and interpretation of the feasibility study findings.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSystematic review\u003c/h2\u003e \u003cp\u003eA comprehensive literature search was performed in the following databases: PubMed, PubPsych, CINAHL, EMBASE, Web of Science and EBSCOhost. Peer-reviewed studies evaluating the effect of prehabilitation on QoL in patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years of age undergoing surgery for colorectal cancer were included. Case reports, case series, letters, and editorials were excluded. No language restriction was employed. A translation system was applied if a study was available only in a foreign language.\u003c/p\u003e \u003cp\u003eThe systematic review was conducted and reported according to the PRISMA guidelines [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The study protocol was registered at Aarhus University, though not publicly available. The searches were performed on the 28th of August 2023 and updated on the 17th of October 2024, in accordance with the AMSTAR guidelines [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Searches span from the earliest available records to the search date. Supplement 1 elaborates on the search string and on the results from the first and second searches.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy selection and extraction\u003c/h3\u003e\n\u003cp\u003eAfter duplicate removal, titles, abstracts and full texts were screened by two independent authors (M.S. and A.T.) using the management software Covidence. Studies identified from conference abstracts or review citations were screened for full text. Any disagreements were resolved by discussion. If consensus could not be reached, the last author made the final decision. The first author (M.S.) performed data extraction and quality assessment.\u003c/p\u003e \u003cp\u003e For quality assessment, a tool specific to each study design was used in accordance with clinical guidelines. For randomised controlled trials (RCTs), the Cochrane-recommended risk-of-bias tool for randomised trials, version 2 (RoB2), was applied [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. For cohort studies, the Newcastle-Ottawa scale (NOS) quality assessment form was used [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The RoB2 tool evaluates risk of bias across five main domains: 1. the randomisation process, 2. deviations from intended intervention, 3. missing data, 4. outcome measurement, and 5. selection of results. Each domain was judged to have low risk, some concerns, or high risk of bias, with an overall judgement derived from the domain-level assessment. The NOS comprises eight items distributed across three domains - Selection, Comparability, and Outcome, each awarded stars for quality. To facilitate comparability across study designs, NOS scores of good, fair, or poor quality were converted to the Agency for Healthcare Research and Quality (AHRQ) standards using previously established thresholds [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Studies were classified as good quality when they achieved high scores across all domains (\u0026ge;\u0026thinsp;3 in Selection, \u0026ge;\u0026thinsp;1 in Comparability, \u0026ge;\u0026thinsp;2 in Outcome). Fair quality corresponded to moderate scores (2/\u0026ge;1/\u0026ge;2), whereas poor quality reflected low performance in any domain (\u0026le;\u0026thinsp;1/0/\u0026le;1).\u003c/p\u003e\n\u003ch3\u003eFeasibility study\u003c/h3\u003e\n\u003cp\u003e This was a non-randomised interventional feasibility study conducted in the Surgical Department, Regional Hospital Randers, Denmark. All patients diagnosed with colon cancer were prospectively enrolled after being screened for eligibility from September 2022 to June 2023. Inclusion criteria were age\u0026thinsp;\u0026ge;\u0026thinsp;18 years and endoscopic macroscopically malignant tumour, later confirmed by pathological examination. Patients were excluded if they were ineligible for the intended curative colonic resection or unable to complete questionnaires due to language or cognitive impairment. Eligible patients were enrolled by a care coordinator on the day of cancer-suspect findings during colonoscopy or within two days by phone. The first author or a specialised care coordinator carried out enrolments. Consent was obtained from all participants after they received oral and written information about the study.\u003c/p\u003e \u003cp\u003ePatients diagnosed at Regional Hospital Randers were assigned to the intervention group, whereas patients referred to the hospital after a colonoscopy at another hospital or private clinic comprised the non-intervention group. All patients were approached and enrolled within three days of the diagnostic colonoscopy.\u003c/p\u003e\n\u003ch3\u003eIntervention and non-intervention groups\u003c/h3\u003e\n\u003cp\u003eThe intervention group received education on the effects of nutrition and exercise on post-surgical recovery, a prescription for nutritional drinks, and a pamphlet containing recipes for homemade supplements. They were encouraged to perform at least 20 minutes of moderate daily exercise (e.g. walking, aerobic training, stretching, or other preferred cardio activities) and to ingest three nutritional drinks (200 mL \u0026sim; 300 Kcal per drink) every day until surgery. If patients had conditions requiring special dietary attention (e.g., diabetes or kidney disease), a dietitian was consulted. The non-intervention group received standard care, including advice on protein-rich nutrition and exercise, until surgery, but without specific guidelines.\u003c/p\u003e \u003cp\u003eAll patients underwent standard diagnostic evaluation, including CT imaging and histopathological confirmation of the cancer diagnosis, followed by an individual care discussion at a local multidisciplinary team meeting. Patients were subsequently seen in the surgical outpatient clinic for treatment planning and offered surgery within 10 days in accordance with Danish healthcare regulations.\u003c/p\u003e\n\u003ch3\u003eOutcomes and measures\u003c/h3\u003e\n\u003cp\u003e \u003c/p\u003e \u003cp\u003eA timeline for outcome assessments is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All patients completed a structured interview at inclusion and at follow-up, approximately 2 weeks post-surgery. The interview included patient-reported outcome measures (PROMs) assessing QoL and compliance with the intervention. The PROMs and additional questions were pilot tested in a focus group to ensure quality and comprehensibility. The final versions are available in Supplementary 2.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome\u003c/h2\u003e \u003cp\u003eThe primary outcome was intervention compliance, assessed through patient self-reporting at follow-up. Participants recorded the number of days they adhered to the prescribed intervention. Compliance was defined as the extent to which patients adhered to the intervention instructions.\u003c/p\u003e \u003cp\u003eA percentage score was subsequently calculated in accordance with the proportion of intake of nutritional drinks: \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{Number\\:of\\:consumed\\:nutritional\\:drinks}{Optimal\\:number\\:of\\:nutritional\\:drinks}*100\\%\\)\u003c/span\u003e\u003c/span\u003e. The same methodology was applied to assess physical activity. There is currently no validated gold standard for defining an acceptable adherence threshold in prehabilitation research. Historically, an arbitrary rate of 80% or higher has been considered good compliance [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAdditional outcomes\u003c/h3\u003e\n\u003cp\u003eSecondary outcomes included both clinical and patient-reported measures (PROMS). Clinical data extracted from medical records comprised weight change during the study period, length of hospital stay (LOS), and surgical and medical complications. Complications were categorised by severity using the Clavien-Dindo classification system, ranging from grade 0 (no complication) to grade 5 (death) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Weight was measured at baseline and on the day of surgery.\u003c/p\u003e \u003cp\u003ePROMs included ad hoc questions exploring patients\u0026rsquo; sense of inclusion within the disease course and self-reported cancer-related symptoms, as well as validated instruments assessing quality of recovery (QoR) by Quality of Recovery-15 (QOR-15) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and QoL using the EuroQol (EQ)-5D-5L and EQ visual analogue scale (VAS) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. All instruments have previously been validated in a Danish cohort [\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The QOR-15 encompasses 15 domains related to post-surgery daily activities and symptoms. Scores range from 0 to 150, with higher scores indicating better post-surgery recovery. The EuroQol (EQ)-5D-5L [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] evaluates five domains (mobility, personal hygiene, usual activities, pain, and anxiety/depression) on five levels, reflecting the patients\u0026rsquo; perception of their health status, while the VAS score evaluated the patients\u0026rsquo; self-rated health on a visual scale ranging from 0 to 100, where 100 is labelled \u0026ldquo;the best health you can imagine\u0026rdquo; and 0 \u0026ldquo;the worst health you can imagine\u0026rdquo;. The EQ-5D-5L and VAS scores were measured at both baseline and follow-up.\u003c/p\u003e \u003cp\u003eEvaluation of patients\u0026rsquo; feelings of inclusion was incorporated in the post-surgery questionnaire. Patients were asked to what degree they felt they had a role in their disease course. Five degrees were presented, ranging from \"not at all\" to \"a very high degree\". Self-reported cancer symptoms were assessed at baseline. Patients were asked about unintentional weight loss in the previous six months and reduced appetite or fatigue in the past 2 weeks.\u003c/p\u003e\n\u003ch3\u003eFollow-up assessment\u003c/h3\u003e\n\u003cp\u003eFollow-up was scheduled at the patients\u0026rsquo; routine clinic appointment 13\u0026ndash;15 days post-surgery, when they were seen for a postoperative check-up and received their final histopathology results of the colon resection (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe first author administered the follow-up questionnaire immediately before the appointment with the surgeon to minimise bias related to prognosis and subsequent treatment decisions.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analyses were performed in R (2023). Descriptive statistics were compiled to characterise the study population, with quantitative data summarised as medians with interquartile range (IQR), and categorical variables summarised as counts and percentages. As a feasibility study, data analysis was primarily descriptive and exploratory. Group differences in categorical variables were assessed using Fisher\u0026rsquo;s exact test or Pearson\u0026rsquo;s Chi-squared test, as appropriate. Continuous variables were compared using t-tests for parametric data and the Wilcoxon rank-sum test for non-parametric data. All analyses were exploratory, as the study was not powered to detect statistically significant differences. Any statistically significant findings should therefore be interpreted with caution, as highlighted in the discussion session.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eSystematic review\u003c/h2\u003e\n \u003cp\u003eThe primary literature search identified 633 records. After removing duplicates, 517 unique records were screened. The PRISMA flowchart is illustrated in Fig.\u0026nbsp;2. Studies were primarily excluded because QoL was not measured. A total of six studies were included in the final analysis [27\u0026ndash;32]. The updated literature search yielded no records for inclusion. Study characteristics are presented in Table\u0026nbsp;1, including the number of participants included, the composition of the interventions, and the quality assessment. Only the cohort study by Li et al. (2012) [31] was assessed as good quality. Two studies [30, 32] received an overall assessment of poor quality, primarily due to a high number of participants lost to follow-up or missing data. The remaining three studies were evaluated as of moderate/fair quality [27\u0026ndash;29].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003eCharacteristics of the prehabilitation programs\u003c/h2\u003e\n \u003cp\u003eThe included studies varied substantially in their prehabilitation interventions with respect to modality (uni-, multi-, or trimodal), duration, and specific intervention characteristics, such as the intensity of physical activity (Table\u0026nbsp;1). Four studies [27, 29\u0026ndash;31] analysed QoL scores comparing a rehabilitation group with a control group. In general, the studies reported high levels of compliance with the prehabilitation program.\u003c/p\u003e\n \u003cp\u003e(Suggesting table 1 here ( attached as a separate file, due to page rotation)\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eQuality of life outcomes\u003c/h2\u003e\n \u003cp\u003eNone of the included studies measured QoL as a primary outcome; it was measured only as a secondary or additional outcome. The studies primarily employed the 36-Item Short-Form Health Survey (SF-36). Table\u0026nbsp;1 provides further details on outcome measures.\u003c/p\u003e\n \u003cp\u003eDue to heterogeneity across studies, particularly in the intervention programs, a meta-analysis could not be performed. Instead, studies have been systematically compared. A detailed illustration of the available data for QoL outcomes is shown in Table\u0026nbsp;2. Four studies [28\u0026ndash;30, 32] reported that prehabilitation had a positive effect on QoL, while two studies [27, 31] found no improvement. One study [29] reported a statistically significant improvement in the prehabilitation group compared to the control group at seven days post-surgery, whereas two studies [27]\u003csup\u003e,\u003c/sup\u003e[31] found no significant differences between the prehabilitation group and the comparison group.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\"\u003e\n \u003ch2\u003eFeasibility study\u003c/h2\u003e\n \u003cp\u003e\u003cem\u003eMissing participants mainly refers to cases where contact could not be established or where patients were not offered the opportunity to participate in time.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eOf the 110 eligible patients, 70 (64%) were included in the study. Of these 63 patients (90%), completed the follow-up (Fig. 3). No significant differences in age or gender were observed between included and excluded patients. Similarly, analysis of dropouts and patients excluded after baseline revealed no differences in baseline characteristics. Baseline characteristics and operative characteristics are shown in Table 3. Overall, no significant differences in baseline characteristics were observed between the two groups. The interval between the initial endoscopy and the surgery date was 2\u0026ndash;3 weeks.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\"\u003e\n \u003ch2\u003eCompliance with the prehabilitation intervention\u003c/h2\u003e\n \u003cp\u003eAfter inclusion, seven (10%) patients withdrew from the study. Among patients who completed the study, the mean compliance score for the nutritional intervention was 80% (IQR 65\u0026ndash;100), and for the physical activity intervention, 89% (IQR 71\u0026ndash;100). A nutritional component compliance score exceeding 80% was achieved by 66% of all patients, with a median compliance value of 100%. Compliance was slightly higher for the physical activity component, with 88% of all patients scoring above 80%, and a median compliance of 100%.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\"\u003e\n \u003ch2\u003eFeeling of inclusion in one\u0026apos;s own course of the disease\u003c/h2\u003e\n \u003cp\u003eIn the intervention group, 38% of patients reported not feeling included, compared with 70% in the non-intervention group. In the intervention group, the majority reported feeling included to a very high (9%), high (16%), or moderate degree (28%), whereas only a minority reported feeling included to a low degree (9%). In contrast, the non-intervention group showed a markedly different distribution, with only one (3%) reporting a very high degree of feeling included, and fewer patients indicating high (10%), moderate (10%), and low (7%) degrees of inclusion.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\"\u003e\n \u003ch2\u003eQuality of life - the EQ-5D-5L\u003c/h2\u003e\n \u003cp\u003eFigure\u0026nbsp;4 shows the distribution of EQ-5D-5L responses at baseline and follow-up (post-surgery) for the intervention and non-intervention groups. At baseline, domain profiles were broadly comparable. Except for anxiety and depression, both groups demonstrated a decline across all severity types from baseline to the post-surgical period.\u003c/p\u003e\n \u003cp\u003ePost-surgery, several notable trends emerged. For usual activities, the non-intervention group demonstrated a marked shift towards moderate-to-severe problems. In contrast, the intervention group retained a higher proportion in the no or only slight problems categories. As for anxiety/depression, the intervention group generally reported a more favourable distribution with a lesser degree of problems compared to the non-intervention group. The intervention group also reported fewer moderate-severe problems than the non-intervention group. The proportion of patients reporting pain/discomfort was comparable post-surgery, although patients in the non-intervention group reported pain/discomfort more frequently at baseline.\u003c/p\u003e\n \u003cp\u003ePost-surgery EQ-VAS scores differed significantly between groups (p\u0026thinsp;=\u0026thinsp;0.047). Scores increased slightly from baseline to post-surgery in the intervention group (from a median of 77.0 to 79.0), whereas they declined in the non-intervention group (from a median of 70.0 to 65.0).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\"\u003e\n \u003ch2\u003e\u003cstrong\u003eAdditional outcomes\u003c/strong\u003e:\u003c/h2\u003e\n \u003cp\u003eAt baseline, patients exhibited a wide range of cancer-related symptoms. Approximately 33% had experienced unintended moderate weight loss and reported a reduced appetite compared to normal. More than half reported some degree of fatigue, and 25% presented with anaemia at diagnosis.\u003c/p\u003e\n \u003cp\u003eFrom baseline to surgery, weight change was small overall, with a median gain of 0.45 kg (IQR: -0.70-1.53). Most patients maintained a relatively stable weight during the preoperative period and did not experience further weight loss. Weight data on the day of surgery were missing for 15 patients (9 in the intervention group and 6 in the non-intervention group). For these patients, weight was obtained on the first or second postoperative day. Only five patients had no post-surgery weight data available.\u003c/p\u003e\n \u003cp\u003eDuring hospitalisation, patients in the two groups showed similar patterns. Patients in the intervention group had a median LOS of 3.5 days (IQR 3.0-8.3), and those in the non-intervention group had a median LOS of 4.0 days (IQR 3.0\u0026ndash;5.0). Generally, the number of perioperative and post-surgical complications was low and evenly distributed between the two groups, as was the case when converted to the Clavien-Dindo classification. The most common post-surgery complications were paralytic ileus, incisional hernia, and anastomotic leakages, with three patients experiencing each outcome. Anastomotic leakage was observed in two patients in the intervention group and in one in the non-intervention group.\u003c/p\u003e\n \u003cp\u003eThe QoR scores were similar between groups, with similar medians and overlapping interquartile ranges. The non-intervention group exhibited a wider score distribution and more low-value outliers, whereas the intervention group showed a more clustered score profile (data now shown).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e This systematic review updates the evidence of the effect of prehabilitation on QoL in patients undergoing surgery for colorectal cancer. Although the included studies reported heterogeneous findings, most suggested potential improvements in QoL associated with prehabilitation, with only one demonstrating a statistically significant benefit compared to controls.\u003c/p\u003e \u003cp\u003eThe feasibility study primarily evaluated compliance with a short-term multimodal prehabilitation programme in patients undergoing surgery for colonic cancer. Overall compliance was high, with 66% of participants achieving\u0026thinsp;\u0026gt;\u0026thinsp;80% compliance with the nutritional component and 88% with the physical activity component. This demonstrates that prehabilitation is feasible in this clinical setting without compromising the planned surgical treatment.\u003c/p\u003e \u003cp\u003eSince this clinical trial was designed as a feasibility study, the secondary outcomes were not intended to support causal inferences and should not be interpreted as evidence of prehabilitation effects. Nevertheless, they provide insights into potential patterns. Consistent with the systematic review, QoL outcomes showed favourable trends following prehabilitation, particularly in domains of returning to usual activities and reducing anxiety and depression, although none reached statistical significance. A modest statistically significant improvement in self-perceived general health was observed at 2 weeks post-surgery. However, this cannot be interpreted as a valid significance test given the relatively small sample size and the study's limited power.\u003c/p\u003e \u003cp\u003eThe findings regarding global QoL are consistent with prior cancer-specific trials and reviews, suggesting less consistent effects on global QoL scores. Earlier studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] more often reported no change or a decline in QoL scores, whereas more recent studies consistently report a relatively small but positive effect of prehabilitation on QoL or differences between groups [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. A systematic review [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] and a Cochrane review [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] focusing exclusively on colorectal cancer have recently been published. However, as these reviews included only RCTs, they were unable to analyse QoL outcomes due to the limited number of eligible studies. To our knowledge, the present review is the first to specifically focus on prehabilitation for colorectal cancer and QoL outcomes across both RCTs and observational studies. The inclusion of diverse study designs inevitably introduced heterogeneity among the included studies, further compounded by variation in prehabilitation modalities, intervention duration, and outcome measures. Similar challenges have been reported in other reviews in this field, including that by Chou et al. [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur systematic review found that only one study [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] had a low risk of bias, while the rest were rated as fair to poor quality. A key methodological limitation across several studies was the small number of patients undergoing prehabilitation. In addition, the assessment of QoL represented a recurring methodological concern, reflecting heterogeneity in measurement instruments and reporting. Despite the use of validated questionnaires across studies, the assessment of QoL remains subjective and may be influenced by recall or timing-related bias. The generally low methodological quality of studies evaluating QoL outcomes could partly reflect that QoL is often considered as a secondary endpoint and assessed over relatively short follow-up periods. In addition, differences in outcome definitions, subdomains, and measurement instruments limit comparability across and reduce the feasibility of pooled analyses.\u003c/p\u003e \u003cp\u003eInternational variation in prehabilitation practices poses challenges for standardising. Programmes differ in duration, modality, target population, and intervention intensity, complicating comparisons between interventions and their effects. The optimal timing for colorectal cancer surgery has been discussed in the literature, with suggestions ranging from 2\u0026ndash;6 weeks [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. In Denmark, the maximum waiting period from final diagnosis of colorectal cancer to surgery is 10 days. However, under recent Danish legislation, surgeons are allowed to postpone surgery to prescribe prehabilitation if deemed necessary to optimise the patient before surgery [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. This feasibility study provides valuable insight, showing that even a brief prehabilitation intervention can achieve high compliance, particularly for the nutritional and physical activity components. This is clinically relevant, as the limited time between diagnosis and surgery is frequently cited as a key barrier to implementing prehabilitation [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCompared with the existing literature, several prehabilitation studies across various cancer types have demonstrated similar compliance rates of 70\u0026ndash;80% or higher [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. This trend was also observed in several multimodal studies included in our systematic review [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Consistent with our findings, several studies have found that compliance with physical activity interventions tends to be higher than with nutritional interventions. The very high compliance observed with the physical activity intervention is likely due to its simple, flexible nature, which allows for individual patient interpretation. From a clinical perspective, these combined findings support the feasibility of incorporating a short-term multimodal prehabilitation into colorectal cancer treatment pathways. We acknowledge that in a trial setting, additional resources may be available, which may contribute to higher patient compliance. Nevertheless, we observed trends toward greater patient involvement in their disease course, suggesting that prehabilitation may promote higher compliance and potential benefits by enhancing patient engagement, empowerment, and preparedness.\u003c/p\u003e \u003cp\u003eStrengths and limitations\u003c/p\u003e \u003cp\u003eThe main strength of this work is the integration of a systematic synthesis of evidence with original feasibility data, enabling combined interpretations. The systematic review followed PRISMA guidelines, and searches were developed in collaboration with a librarian and employed a clearly defined search strategy across a comprehensive range of databases without language restrictions. Reference lists were screened, and appropriate quality assessment tools were carefully selected to suit each specific study design.\u003c/p\u003e \u003cp\u003eA key strength of the feasibility study is the low drop-out rate (10%). Patients who withdrew did not differ significantly from those who completed the study in terms of age, gender, ASA classification, performance status, or BMI. Another notable strength is the inclusion of patient-centered outcomes that go beyond traditional QoL measures, such as feelings of inclusion and QoR, assessed within a non-randomised controlled design. Although patient involvement in care is increasingly recognised as a crucial factor for satisfaction and perceived benefit, it remains underreported in prehabilitation research.\u003c/p\u003e \u003cp\u003eThere are some limitations to our studies. Within the systematic review, the broad inclusion of study designs inevitably introduced heterogeneity among the included studies. Although the search was updated in 2024, publication of the findings was delayed by over a year, and no additional updates were made.\u003c/p\u003e \u003cp\u003eThe feasibility study was non-randomised and not powered to assess efficacy outcomes, limiting causal inference drawing and reducing generalisability. The small sample size represents an additional limitation. Although the inclusion rate was 64%, legal constraints prevented data collection from non-participants, thereby preventing statistical comparisons. Consequently, selection bias cannot be ruled out. Prehabilitation is considered particularly beneficial for frail patients [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. However, such patients are challenging to involve in research. It is possible that some very frail patients were not included in the study, potentially introducing selection bias and affecting internal validity. Although no statistically significant differences in baseline characteristics were observed between the intervention and non-intervention groups, a trend toward higher baseline ASA scores in the non-intervention group should be acknowledged. Finally, compliance scores and PROMS were primarily based on self-reported data and may be subject to recall bias.\u003c/p\u003e \u003cp\u003eFuture aspects\u003c/p\u003e \u003cp\u003eWhile our prehabilitation intervention is feasible to implement, the future application of prehabilitation on a larger scale faces several challenges, particularly in logistics and resource allocation within a hospital's daily workflow. Previous research in this field suggests that applying a multimodal or trimodal prehabilitation lasting for at least 3 weeks is necessary to achieve full benefits [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. To achieve greater consistency, there is a need for consensus on the definitions of prehabilitation, intervention modalities, and the screening tools employed to determine when to implement a prehabilitation program. A recent Delphi study by Fish et al. [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] proposed a more standardised approach to prehabilitation and may provide guidance for future trials. Greater standardisation could lead to higher-quality and more homogeneous evidence, facilitating evidence synthesis and improving the translation of prehabilitation research into patient benefit. Obstacles also include the lack of qualified staff and restricted financial resources. Moreover, there is a need for studies evaluating the economic impact of prehabilitation in this patient population, even though early prehabilitation interventions may be cost-effective by reducing the burden of postoperative complications.\u003c/p\u003e \u003cp\u003eTo evaluate the causal effects of prehabilitation on outcomes such as QoL, post-surgery complications, QoR, and patients\u0026rsquo; sense of inclusion, more high-quality RCTs with large sample sizes are needed. Although satisfactory compliance was observed, the effectiveness of short-term prehabilitation should be evaluated in longer and more comprehensive programmes. In addition, clearer guidelines are needed on when curative surgery should be postponed in favour of prehabilitation and how best to identify patients most likely to benefit.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, our findings suggest that, while robust evidence for definitive effects of prehabilitation on QoL remains limited, prehabilitation appears acceptable, implementable, and potentially beneficial from a patient perspective. This supports further evaluation in adequately powered trials with QoL as a primary outcome. The studies included in the review showed substantial heterogeneity and, at times, conflicting results, underscoring the need for additional high-quality research. Our feasibility study further demonstrated favourable trends across PROMs, including QoL-related domains and patients\u0026rsquo; perceived feelings of inclusion. Future research should aim to establish consensus-based intervention frameworks, incorporate economic cost-benefit analyses, and develop guidance on optimal timing, duration, and patient selection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interests:\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eAddress correspondence to\u003c/h2\u003e \u003cp\u003eMichelle Vestergaard Stadelhofer, Aarhus University, Ny Munkegade 120, Building 1521, 1st floor, DK-8000 Aarhus C. [email protected] or [email protected]\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFundings:\u003c/h2\u003e \u003cp\u003e This project was funded by Randers Regional Hospital, the Louis-Hansen fund, the Health Research Foundation of Central Denmark Region, and the Family Hede Nielsen fund.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.V.S., H.R.D, A.V.T, K.J.E, conceptualised and designed the study. M.V.S developed the data-collection instruments, while A.V.T, K.J.E assisted and revised the data-collection instruments. M.V.S and A.V.T conducted data collection. M.V.S carried out the analyses, drafted the initial manuscript, and H.R.D, A.V.T, K.J.E critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003e A special thanks to all study participants for making this study possible, and to the coordinating nurses Jytte W\u0026uuml;rtz, Birgitte Christiansen, and Anne Majholm for their indispensable assistance with patient enrolment and data collection. Sincere thanks also to Thomas Skelde Kr\u0026oslash;jmand for expert statistical guidance.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are available within the article and its Supplementary Information. The questionnaires used or created are available in supplementary 2. Any additional data might be available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e(WHO), W.H.O (2020) All cancers - fact sheet, Globocan 2020. International agency for Research on Cancer\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmoll HJ et al (2012) ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol 23(10):2479\u0026ndash;2516\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFagard K et al (2016) The impact of frailty on postoperative outcomes in individuals aged 65 and over undergoing elective surgery for colorectal cancer: A systematic review. J Geriatr Oncol 7(6):479\u0026ndash;491\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorten FS, Hartwig IG (2020) [Colon cancer surgery in the high-risk patient]. Ugeskrift l\u0026aelig;ger 182(22):V10190572\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarli F, Zavorsky GS (2005) Optimizing functional exercise capacity in the elderly surgical population. Curr Opin Clin Nutr Metabolic Care 8(1):23\u0026ndash;32\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMolenaar CJL et al (2019) Prehabilitation, making patients fit for surgery \u0026ndash; a new frontier in perioperative care. Innovative Surg Sci 4(4):132\u0026ndash;138\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFinnerty CC et al (2013) The Surgically Induced Stress Response. J Parenter Enter Nutr 37(5S):21S\u0026ndash;29S\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTevis S, Kennedy G (2016) Postoperative Complications: Looking Forward to a Safer Future. Clin Colon Rectal Surg 29(03):246\u0026ndash;252\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDurrand J, Singh SJ, Danjoux G (2019) Prehabilitation Clin Med 19(6):458\u0026ndash;464\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHughes MJ et al (2019) Prehabilitation Before Major Abdominal Surgery: A Systematic Review and Meta-analysis. World J Surg 43(7):1661\u0026ndash;1668\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillis C et al (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(2):391\u0026ndash;410e4\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHijazi Y, Gondal U, Aziz O (2017) A systematic review of prehabilitation programs in abdominal cancer surgery. Int J Surg 39:156\u0026ndash;162\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoher D et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336\u0026ndash;341\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePage MJ et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. 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BMJ, : p. m4087\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSundhedsstyrelsen (2022) Pakkeforl\u0026oslash;b for kr\u0026aelig;ft i tyk- og endetarm. Sundhedsstyrelsen, Editor\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFuryk C et al (2021) Prehabilitation for Frail Patients Undergoing Colorectal Surgery: Lessons Learnt From a Randomised Feasibility Study. Front Rehabilitation Sci, 2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJensen BT et al (2019) Implementing a Multimodal Prehabilitation Program to Radical Cystectomy in a Comprehensive Cancer Center: A Pilot Study to Assess Feasibility and Outcomes. Urol Nurs 39(6):303\u0026ndash;313\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarlsson E et al (2019) Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery \u0026ndash; A randomized controlled design. 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BJS, 111(6)\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Colorectal-cancer, Prehabilitation, Feasibility, Systematic review, Quality of Life (QoL), PROMS","lastPublishedDoi":"10.21203/rs.3.rs-9451596/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9451596/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo evaluate the feasibility of short-term prehabilitation and its impact on quality of life in patients with colorectal cancer through a systematic review and a feasibility study.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003e The systematic review was conducted in accordance with the PRISMA guidelines. PubMed, PubPsych, CINAHL, EMBASE, Web of Science and EBSCOhost were searched for studies evaluating quality of life in colorectal cancer patients undergoing prehabilitation. We conducted a prospective non-randomised interventional feasibility study, with a two-week post-surgery follow-up, enrolling patients diagnosed with colon cancer.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe systematic review included six studies from 517 unique records for final analysis. Among six studies, evidence for quality-of-life benefits of prehabilitation was conflicting but predominantly favourable, with generally low-to-moderate study quality and substantial heterogeneity. In the feasibility study 110 patients were eligible for inclusion; 70 (64%) were included, and 63 completed the entire study. Of the 32 patients in the intervention group, compliance\u0026thinsp;\u0026gt;\u0026thinsp;80% was observed in 66% (nutrition) and 88% (physical activity) of patients, with a median compliance of 100% for both. Quality-of-life outcomes were explored as secondary measures and showed favourable trends following prehabilitation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eEvidence on the effect of prehabilitation on quality of life in colorectal cancer remains inconsistent; Our feasibility study shows that short-term multimodal prehabilitation is feasible and supports the need for adequately powered trials.\u003c/p\u003e","manuscriptTitle":"Prehabilitation for Colon Cancer Surgery: A Systematic Review of Quality-of-Life Outcomes and a Feasibility Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 09:58:59","doi":"10.21203/rs.3.rs-9451596/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-14T16:23:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T13:28:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T17:15:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40485415959905547297708543592338331061","date":"2026-04-24T22:58:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97294186621101271688037615776900970912","date":"2026-04-24T19:33:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84431727435036339438134164398592015793","date":"2026-04-22T19:27:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T19:00:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-22T00:49:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-22T00:49:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Colorectal Disease","date":"2026-04-17T16:51:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e8be6030-b183-4dba-bd34-7c317e326f0b","owner":[],"postedDate":"May 4th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-14T16:23:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T13:28:55+00:00","index":19,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T17:15:10+00:00","index":18,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T16:55:52+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-04 09:58:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9451596","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9451596","identity":"rs-9451596","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}