A systematic review of multimodal prehabilitation in breast cancer

Purpose Breast cancer is the most prevalent malignancy in women. Prehabilitation may offer improvements in physical and psychological wellbeing among participants prior to treatment. This systematic review aimed to determine the efficacy of prehabilitation in participants diagnosed with breast cancer. Methods A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Studies exploring the impact of prehabilitation in participants with breast cancer were included. Studies were assessed independently according to pre-eligibility criteria, with data extraction and methodological quality assessed in parallel. Results 3184 records were identified according to our search criteria, and 14 articles were included. Articles comprised of quantitative randomised controlled trials (n = 7), quantitative non-randomised studies (n = 5), a qualitative study (n = 1), and a mixed-method study (n = 1). The majority of selected studies completed exercise programs (n = 4) or had exercise components (n = 2), with two focusing on upper-limb exercise. Five articles reported complementary and alternative therapies (n = 5). Two articles reported smoking cessation (n = 2), with a single study reporting multi-modal prehabilitation (n = 1). Mostly, prehabilitation improved outcomes including physical function, quality of life, and psychosocial variables (P < 0.05). The qualitative data identified preferences for multimodal prehabilitation, compared to unimodal with an interest in receiving support for longer. Conclusions Prehabilitation for patients with breast cancer is an emerging research area that appears to improve outcomes, however, ensuring that adequate intervention timeframes, follow-up, and population groups should be considered for future investigations. Implications for Cancer Survivors The implementation of prehabilitation interventions for individuals diagnosed with breast cancer should be utilised by multidisciplinary teams to provide holistic care to patients as it has the potential to improve outcomes across the cancer care trajectory. Supplementary Information The online version contains supplementary material available at 10.1007/s10549-022-06759-1.


Introduction
Cancer incidences and mortality rates continue to grow across the world [1]. Evidence identifies that 2.1 million new breast cancer (BC) diagnoses are made annually accounting for one in four cancers among females. Breast cancer is the most commonly diagnosed cancer in females and the leading cause of death [1] globally. The highest BC incidence rates include Australia with a 5-year relative survival rate (2013-2017) of 92%. In 2021, it was estimated that 20,030 new cases of BC will be diagnosed in Australia [2]. Due to improved survival rates over the past two decades (1988)(1989)(1990)(1991)(1992) and 2013-2017 improved 76-92% [2], respectively), many individuals diagnosed with BC are now living with the long-term effects of the diagnosis including debilitating treatment effects with a number of unmet supportive care needs [3,4].
Compared to individuals without cancer, BC survivors are at an increased risk of developing anxiety and depression, fear of recurrence, sexual dysfunction, and relationship issues [5,6]. It has also been reported that the transition from being a BC patient to a survivor can be associated with increased physical and psychological challenges associated with unmet needs [5]. Programs to support the complex needs of individuals with BC are currently ad hoc and urgently need evaluation and optimisation to support this ever-growing population from diagnosis through to survivorship [4]. Supportive care considers and addresses the physical, emotional, social, spiritual, and informational needs of people diagnosed with cancer throughout the disease trajectory [7]. The delivery of supportive care for people diagnosed with BC continues to be suboptimal [8]. People and their families are required to seek out multiple interventions which focus on improving quality of life (QOL) and rehabilitation which has significant financial impact [9][10][11][12].
Strong evidence suggests that lack of physical activity (PA) is associated with an increased risk of BC and poorer outcomes for those diagnosed [13][14][15]. Physical inactivity and unhealthy behaviours contribute to the disease burden for individuals with BC and the Australian Burden of Disease study indicated that physical inactivity contributed 6.4% of the burden [16,17]. There is an inverse relationship between PA (a modifiable risk factor for BC) and all-cause mortality, BC-related death, and BC events [18]. Appropriate PA interventions may be important for people diagnosed with BC and their families to reduce mortality and BC recurrence [19]. The Clinical Oncology Society of Australia's (COSA) position statement recommends that people going through cancer treatment participate in 150 min of moderate intensity PA, or 75 min of vigorous activity per week, along with two resistance-based sessions per week [20], which is the same recommendation published by the World Health Organisation (WHO) for healthy individuals [21]. COSA also recommends that optimal care is achieved by matching services and resources to the individual persons' requirements, which are then easily accessible and integrated with the multidisciplinary team (MDT) [22]. Even though PA guidelines and recommendations exist for participants with BC, they do not address the complexities of their overall supportive care needs including prior to surgery in the prehabilitation period. Prehabilitation is acknowledged to be the presurgical period where effective programs could be used to optimise the physical and emotional status of the patient before the stress of their operation and could be key to addressing participant's individual needs [23].
The model of survivorship care published by COSA in 2016 [24] suggested that to achieve optimal care, services, and resources need to be carefully matched to the specific persons needs and concerns, and it needs to be accessible to the person and integrated across the MDT [24]. Currently gaps remain and this level of care is not accessible to many individuals with BC across models of care and in current survivorship pathways [25][26][27]. Medical follow-up often overlooks a person's psychosocial issues and important referral needs, leading to suboptimal supportive care [28,29]. This will then be further impacted by the lack of guidance for the person as their needs have not been highlighted and addressed. Prehabilitation could be used as a time to address the needs of individuals with BC by using the most appropriate tools to identify necessary multimodal referral pathways [30][31][32]. The prehabilitation phase of treatment could be utilised to identify patient concerns, establish referral pathways, and set review timeframes to ensure a smooth cancer treatment journey [24].
Multimodal interventions which include MDT care are inconsistent and underutilised for individuals with BC [3]. The inclusion of multimodal, MDT programs recognises the need for supportive care programs which includes a holistic approach to peoples' wellness across their personal BC recovery [33]. Therefore, the aim of this systematic review was to determine what supportive care prehabilitation programs exist to assist those diagnosed with BC and what outcomes were reported.

Methods
This systematic review has been reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [34] and was registered in PROSPERO International Register of Systematic Reviews (CRD42021259463), available from https:// www. crd. york. ac. uk/ prosp ero/ displ ay_ record. php? Recor dID= 259463.

Literature search
An electronic database search using combinations of MeSH and free-text words for "breast cancer " and "prehabilitation" were undertaken by an experienced health information specialist (MT) using the following databases: CINAHL and Medline on EBSCOhost platform, Cochran Library (DSR and CENTRAL), Scopus, and Web of Science Core Collection and were conducted on 1 July, 2021 and updated on the 21 March, 2022. The Participant, Intervention, Comparator, and Outcome (PICO) framework [35] was used to define the inclusion criteria.

Participants
Participants were included if they were > 18 years, had a diagnosis of primary BC, and participated in a prehabilitation program of any kind prior to treatment.

Intervention
Clinical trials, cohort studies (retrospective and prospective), and case control studies that explored prehabilitation programs for participants with BC prior to invasive surgery. Studies developing, validating, updating, evaluating, or comparing prediction models of BC were eligible. Only studies published in English were included. The following articles were excluded: Review articles and studies published in languages other than English, protocols, conference abstracts, and clinical trial registrations were also excluded. Eligible studies were characterised into subgroups based on the type of prehabilitation program.

Comparators
Studies that compared prehabilitation to usual care or no prehabilitation or another intervention were included.

Outcomes
Studies that evaluated the feasibility and/or the effectiveness of the prehabilitation intervention(s) on health-related outcomes (e.g. quality of life, physical outcomes) were eligible.

Data extraction and management
Search results that were identified during the electronic database search were transferred to Covidence, a systematic review software (Version 2579, Melbourne, Australia) and duplicate titles removed. Title and abstracts were resolved by five authors, and conflicts were by discussion. Articles then considered potentially eligible were moved to the fulltext screening. Full-text articles were independently assessed by a minimum of two reviewers. All authors extracted the following outcomes compared to baseline from each study into table format; population, outcomes, physical function assessments, clinical assessments, patient-reported outcome measurement, and findings. All data extraction was quality checked by a second reviewer.

Assessment of study quality
Methodological quality assessment of the included studies was completed using the Mixed Methods Appraisal Tool (MMAT 2018) [36]. The quality assessment was carried out by all authors during the data extraction phase, and a second author then quality checked assessments on all articles, discussing any disagreements.

Study characteristics
The characteristics of the included studies are described in Table 1. A total of 1,568 participants (quantitative participants n = 1,529; qualitative participants n = 11; mixedmethods participants n = 28) were included. Noteworthy, there was only one male participant included across all studies, and it was unclear whether this participant completed the intervention or was lost to follow-up. The included participants were heterogeneous in clinical characteristics including cancer stage, type of BC, and type of treatment, which included surgery and surgery type, chemotherapy, radiotherapy, and hormonal therapy, which deemed the completion of a meta-analysis inappropriate. For the quantitative studies, the samples ranged from 41 to 400, with an average age range 42-63 years. The sample size for the qualitative study was 11 and the age range was 40-72 years, with the mixed-methods study included 28 participants, with a mean age of 54 ± 10.98. The included studies were carried out in United States of America [37,40,41,43], Canada [38], Sweden [39], Japan [42,44,45], Denmark [46,47], China [48], United Kingdom [49], and Romania [50].

Quality appraisal results
The results of the quality appraisal of the articles are presented in Table 2, where the quality assessment was carried out by all authors during the data extraction phase, and a second author then quality checked assessments on all articles, discussing any disagreements. After this process, it was found that all studies reported a generally low risk of bias. All studies reported a low risk of bias for the first two domains, which describe the outcomes of the studies addressing the research questions. Both the qualitative [46] and mixed-methods [38] studies reported a low risk of bias across all domains. For the quantitative studies, all groups were found to be comparable at baseline, and the reported outcome data were complete. An unclear bias risk was observed for some RCTs for outcome assessors being blinded to the intervention provided [40,41,44], and for participants adhering to the assigned interventions [45,47], where this information was not described within the articles. Further, unclear bias was reported for all non-randomised quantitative studies [37,42,43,48,49] due to no discussion of accounting of confounders in the study design. A high bias risk was reported for a single study [39], as they stated that the study was not blinded to assessors, and the participants did not adhere to the intervention. Finally, while it is not defined as a quality criteria, it should be noted that one randomised study did not include a control group, but rather an additional intervention which acted as the comparator [40].

Prehabilitation findings overview
A wide variety of prehabilitation interventions were completed for the included studies, as described in Table 3. For the selected studies, the majority completed exercise programs [37,38,40,43,49] or had a component of exercise [39,42,48], with two studies focusing on upper-limb exercise specifically [37,38]. An additional two focused on smoking cessation [46,47], with a single study reporting on multimodal prehabilitation [49], and a range of complementary and alternative therapies [41,44,45,48,50]. The program delivery methods varied and ranged from the             week. An overview of the findings of these interventions can be found in Table 4.

Upper limb evaluation in prehabilitation
Five studies explored the effects of prehabilitation on upper-limb (UL) dysfunction following surgical treatment for BC [37,38,42,43,49]. Study sizes ranged from 28 to 162 participants, with all research time points commencing pre-operatively but ending at different time points (6 weeks, Heiman et al.   The mind-body control participants were given a book and asked to listen to an associated guided imagery audio guide twice a day     SPOFIA; DASH SPOFIA and grip strength were significantly improved in the I who underwent ALND; no significant improvement in the I who underwent SLNB No significant differences in arm girth, shoulder ROM, or DASH were seen between groups with ALND. Significant differences in change in SPOFIA score over time were noted between the ALND I and C groups (F value = 3.34; P = 0.02) A significant difference over time in the difference in mean grip strength was seen between normal and affected sides in both I and C groups (F value = 2.77; P = 0.04), indicating significantly improved grip strength over time in the ALND I group compared to the ALND C group No significant differences in arm girth, shoulder ROM, grip strength, SPO-FIA, or DASH were identified between SLNB groups Not assessed ULDQ Shoulder abduction, external rotation, flexion, and composite ROM decreased from baseline to 1 month (P < 0.0001), improved from 1 month to 3-6 months (P < 0.0001), and improved further from 3-6 to 12 months (P < 0.0001) Internal rotation ROM had a significant decrease from baseline to 1 month (P < 0.04), and a significant improvement from 1 and 3-6 months to 12 months (P < 0.03) Shoulder strength had a significant decrease at 1 month (P < 0.001) Greater pain at 1 month than baseline (P < 0.001) Shoulder abduction, flexion, external rotation, and composite ROM significantly correlated with all subcategories of the ULDQ (P < 0.02); internal rotation did not Significant difference in limb volume found between sub-clinical lymphedema and no lymphedema subgroups at 12 months (P < 0.045) Tamaki et al. 2017 Japan [44] Primary endpoint: QOL, which was assessed EORTC QLQ-C30 Secondary endpoints: necessity of hypnotics, vital signs (blood pressure and heart rate), adverse events, and patient perception of the experience Vital signs (blood pressure and heart rate) Not assessed EORTC QLQ-C30; use of hypnotics; patient experience No statistically significant differences between groups in the EORTC QLC-C-30 at the surgery day. Differences in physical functioning and role functioning detected for post-operation day 1 but did not reach statistical significance (P = 0.08 and 0.09, respectively) No effects of aromatherapy were observed for blood pressure, heart rate, and the rate of hypnotic using (all P  Some participants experienced that the smoking intervention motivated smoking cessation for a short period before or immediately after surgery; however, they quickly resumed their habit, or alternatively, attempted but were unable to stop smoking at all Specifically, anxiety peaked in the days prior to surgery and to getting the results of surgery. Brief preoperative smoking intervention in this context did not sustain abstinence in these participants ''Absolutely, I'm never going to smoke another cigarette, ever again. But going through the hospital system and all the waiting and pressure and worrying. Then you start to think: If I smoke just one cigarette here and another one there, it won't harm anything, because you need it.'' Enacting a duty of responsibility The participants who stopped smoking experienced doing so as an enactment of a duty of responsibility towards themselves and those nearest to them ''I want to be well again and live a healthy life. The most important thing is to be able to be here for my kids and not to pollute them with my smoking.'' Not assessed NRS (for pain intensity); NRS (for intensity of psychological symptoms) Pain intensity significantly lower in I than C immediately after waking, at T2, T3, T4, and T5 after surgery (P < 0.05). I recorded maximum pain intensity 4/10 NRS. C recorded maximum pain intensity 8/10 NRS. Difference between mean scores of groups approximately 5/10 NRS immediately after waking (I: 1.  12 weeks, and 12 months). The heterogeneity observed for the designs of these studies limits the understanding of the long-term impact of prehabilitation on UL dysfunction. Participants partook in prehabilitation exercise programs and education, face to face or by video, and in some cases were compared to standard care with respect to UL dysfunction. Standard care was not necessarily discussed, compared, or explained in the research. Three studies [38,42,49] utilised the Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, measuring the ability of the participants to complete upper-extremity activities, which allowed consistency in results. The Shoulder Pain and Disability Index (SPADI), Upper Limb Disability Questionnaire (ULDQ), and Subjective Perception of Post-Operative Functional Impairment of the Arm (SPOFIA) were other tools utilised to measure UL functionality.
It was identified that UL pain [37] and DASH score [38] increased over time from baseline measurements, indicating an increase in UL disability. Similarly, there was a decrease in shoulder range of motion between baseline and measurements at one month; however, the range of motion improved at all subsequent time points [43]. While one study reported no significant changes between groups for SPADI [49], improved grip strength and SPOFIA score were reported in patients who had participated in prehabilitation and who had undergone axillary dissection [42]. However, no significant improvements were observed following prehabilitation in patients having sentinel node biopsy [42].

Exercise and physical activity programs (excluding UL only)
Two studies included a supervised exercise program within the BC prehabilitation intervention which included both aerobic and resistance training [38,40], with one of these studies completing UL-specific resistance training [38]. These interventions consisted of 30-40 min aerobic exercise 3-5 days per week, with 2-3 UL resistance training days a week [38], and two 60-90 sessions a week incorporating both aerobic (30-40 min) and resistance (20 min) exercises [40] (Table 2). Both studies identified that disability increased from baseline to 12 weeks post-operatively [38], and a decrease in role functioning over time [40] despite the exercise programme. However, an increase in the sixminute walk test (6MWT) was observed from baseline to pre-operatively indicating an increase in aerobic fitness prior to surgery [38], with improvements made for anxiety and stress in the exercise group [40]. Interestingly, the interviews completed by Brahmbhatt et al. [38] revealed that the participants and the healthcare professionals were in favour of the program. Participants suggested that the programme is offered to all surgical candidates, as it helped them to regain control over the preoperative period and it facilitated postoperative recovery by educating on postoperative rehabilitation protocols. A preference for multimodal prehabilitation was highlighted, due to the request for the inclusion of dietetics and psychological interventions.

Complementary and alternative therapies
A range of studies provided complementary and alternative therapies as part of their prehabilitation interventions. These included psychosocial [41], aromatherapy [44], traditional medicine [45], comprehensive nursing [48], and relaxation technique [50] interventions, with another study utilising a mind-body prehabilitation program as a comparison to their prescribed exercise intervention [40]. The duration of these studies was short term and ranged from one day to one-month post-surgery, with sample sizes ranging from 41 to 168 participants. All but one study [48] was a randomised controlled trial, with the comparator groups completing a standard care that was unspecified by the authors [41,44,50]. This is with the exception of Tanaka et al. [45] who prescribed water to participants in place of the traditional medication, and Tian et al. [48], who described what the 'Conventional Nursing Mode' their control group received entailed. Further, Knoerl et al. [40] did not utilise a control, but rather two groups who received different interventions.
A range of patient-reported outcomes were assessed in these studies, with only one study reporting no significant differences between groups for any outcomes, resulting in aromatherapy potentially not being successful for prehabilitation in this population [44]. The mind-body intervention prescribed by Knoerl et al. [40] resulted in improvements in cognitive decline, however, also reported a significant decline in role functioning over time [40]. The comprehensive nursing intervention resulted in higher mental state and quality of life scores, and lower anxiety, depression, and pain scores [48], while participating in relaxation techniques and psychological counselling also resulted in lower pain intensity and significantly lower postoperative psychological symptoms [50].
To support these patient-reported outcomes, two studies collected additional information on the participant's biomarkers. Larson et al. [41] reported a decrease in "cancer-related disgust", and while there were no significant changes to natural killer cell activity, it was observed that interferon-gamma did not substantially decrease in the intervention group, suggesting that the psychosocial intervention may have played a role in preventing treatment-related immunosuppression [41]. Additionally, the prescription of traditional medicine significantly reduced Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and State-Trait Anxiety Inventory-General (STAI-T) symptoms in the intervention group [45]. Tanaka et al. [45] reported significantly lower salivary alpha-amylase immediately prior to surgery, supporting the decreased patient-reported anxiety [45].

Cessation of smoking
Two publications reported on the same study that explored the cessation of smoking interventions before and after BC surgery [46,47], reporting on both the qualitative [46] and quantitative [47] outcomes of the intervention. Participants were required to attend a single session of counselling and were provided with nicotine replacement therapy. The quantitative findings identified that more participants in the intervention arm reported continuous smoking cessation across a short-term surgery period [47]. Alternatively, no difference was observed between the control and intervention groups in postoperative complication rate, wound complication rate, or long-term smoking cessation [47]. Thomsen et al. [46] utilised semi-structured interviews for the qualitative aspect of this research and reported that the intervention encouraged the participants to reflect on their smoking, which encouraged short-term cessation for their surgery [46]. However, it was revealed that a prolonged intervention duration, both pre-and post-operatively may be more effective in supporting smoking cessation in this population [46].

Multimodal prehabilitation
One of the included studies explored the impact of multimodal prehabilitation in participants with BC [49]. The interventions included self-management topics related to nutrition, smoking cessation, psychosocial support, and a tailored exercise program [49]. Overall, 81% (n = 61) of participants with BC chose to participate, with n = 20 participants declining the multimodal prehabilitation intervention being assigned to the control group. Noteworthy, the researchers did not clearly define what the current standard of care was in the control arm, and therefore, bias is possible in study outcomes. Overall, there were no statistically significant differences in length of hospital stay, rates of readmissions, post-treatment complications or health-related QOL scores, with the exceptions of anxiety levels in favour of the intervention arm [49]. The maximum follow-up time point post-surgery was six weeks [49], which limits the understanding of the impact of multimodal prehabilitation into survivorship.

Discussion
Prehabilitation is an emerging research area [51]. The time before treatment can be used to introduce self-management support to optimise recovery in individuals with BC. At present, there seems to be a narrow focus on the type of programs delivered post-treatment and variations in standard care, making it difficult to compare interventions and outcomes. Prehabilitation had a positive impact on health-related outcomes of participants diagnosed with BC, and one study reported reduced anxiety, stress, and insomnia scores [40]. It was identified that the prehabilitation period may be the ideal time period to determine the needs of individuals with BC [38]. Ensuring timely referrals would likely reduce fatigue, disability of the arm and hand, and improve overall psychological and physical fitness and strength post-operatively. The focus at present is on a single form of treatment/support which for most studies was lacking a holistic approach to the participant's care and input from the muti-disciplinary team. There is an opportunity for improved clinical, psychological, physical, and quality of life outcomes with the implementation of prehabilitation in BC. This review determined that to date, the evidence in prehabilitation in BC is emerging.
Multi-modal prehabilitation should be considered by clinicians within clinical service re-design [23]. Given that there is only a short timespan between diagnosis and the first line of treatment, it is important to consider how the program would work and how the delivery of the different components could compliment the treatment. Given that there was only one multimodal intervention [49] within this review, it is difficult to draw conclusions on what this program should look like. The program was feasible with 80% of patients opted to participate and was found to reduce anxiety levels [49]. The follow-up period was only six weeks which means that long-term effects of the program cannot be determined. Future programs should consider a longer-term follow-up period in their study designs. Partners could also be an influence on the success of prehabilitation programs [33]; however, to date, there is limited evidence.
Multimodal prehabilitation should consider all facets of the person and include support from oncology specialist nurses and programs such as exercise, psychology, and nutrition and educational components as needed by the individual. Long-term physical and psychological wellness is key to recovering from BC treatments and its side effects. Implementing a prehabilitation program could ensure people are well supported as they go through this period of their lives.
Quitting smoking has been shown to increase survival, improve healing times and surgical outcomes [52] among BC patients, although it is not known what support is needed and when the best time to deliver it is [53]. Smoking cessation in this review focused on education and counselling with varying results. The support may be better integrated across the diagnosis and treatment phase when it is best for the patient, however, should form part of an early conversation with the patient.
As part of holistic care for participants with BC prehabilitation, UL assessment and therapy should form part of prehabilitation given that UL dysfunction is a common effect of treatment. UL pain was shown to increase over time indicating that disability will also increase for many. This shows the need to support the patient through the treatment phase and beyond even with a successful prehabilitation program. Understanding the impact of movement and exercise over this period should be a high priority and future direction for research. Exercise improved anxiety and stress and participants and health care workers were supportive of the program and believed it helped with their recovery. The qualitative exploration identified that participants wanted multimodal interventions rather than unimodal.
Complementary and alternative programs may be supportive of the goal of prehabilitation in people with BC. These included psychological support, aromatherapy, traditional medicine, comprehensive nursing, and relaxation techniques including mind-body work. Improvements in cognition, mental state, quality of life, decreased anxiety, depression, and pain were attributed to complementary therapies, in all but one study in this review.
While some significant changes were observed in this review there are limitations that must be considered. Studies did not always report the type of BC (or treatment/ specific surgery details), increasing the heterogeneity, and not allowing us to draw more accurate conclusions for the type of participants, including male participants. However, what we have shown is that prehabilitation could improve many outcomes for people with breast cancer and should be further explored.

Clinical implications
This review makes an important contribution which has acknowledged for the first time that significant heterogeneity exists in prehabilitation models of care in terms of the mode of administration, duration, and outcome measures used to quantify its impact. Importantly, there has been a lack of focus on the outcomes of including partners as critical companions during this distressing phase of the cancer care continuum. Members of the multidisciplinary team caring for people affected by BC are encouraged to use the findings of this review to inform holistic models of care.

Conclusion
Prehabilitation for patients with BC is an emerging research area that appears to improve outcomes; however, ensuring adequate intervention timeframes, follow-up, and population groups should be considered for future investigations. Researchers and healthcare professionals still do not know the contribution of the effect of unimodal influence on study outcomes compared to multimodal interventions, and what approach is most effective to optimise clinical, physical, and psychological outcomes.

Future research
Based upon the findings of this review, future RCT multimodal prehabilitation programs are needed and considerations should be given to include partners. There was a lack of prospective longitudinal follow-up, limited understanding of how different clinical and demographic variables may have a mechanistic effect on study outcomes. Of clinical relevance, there was only one male participant represented across included studies, and therefore, future research should be inclusive of all genders including the LBGTQIA + patient populations. Future studies should consider embedding robust cost-effectiveness evaluation in all future prehabilitation studies.