The Role and Scope of Prehabilitation in Cancer Care

ARTICLE IN PRESS Seminars in Oncology Nursing 000 (2019) 150976

Contents lists available at ScienceDirect

Seminars in Oncology Nursing journal homepage: https://www.journals.elsevier.com/seminars-in-oncology-nursing

The Role and Scope of Prehabilitation in Cancer Care Alexander Lukez, BS*, Jennifer Baima, MD University of Massachusetts Medical School, Worcester, MA

A R T I C L E

I N F O

Key Words: Rehabilitation-Nursing Neoplasms Exercise Counseling

A B S T R A C T

Objectives: To recognize cancer prehabilitation as a pretreatment regimen to increase functional status for patients requiring cancer treatment. This article presents current evidence addressing the efficacy and benefits of prehabilitation regimens in different cancer survivor populations. Data Sources: Studies and case reports in the PubMed database. Conclusion: Cancer prehabilitation may improve outcomes. Prehabilitation may include targeted or wholebody exercise, nutrition, education, psychologic counseling, and smoking cessation. Opportunities exist to further improve access to and delivery of multimodal prehabilitation, and nurses play a critical role in connecting patients to these services. Implications for Nursing Practice: Oncology nurses who are knowledgeable of cancer treatment-related effects are poised to assess survivors for existing impairments, advocate for prehabilitation for existing and potential morbidities, and monitor functional status over time. As patient educators, they are key to informing cancer survivors about the role of prehabilitation. © 2019 Elsevier Inc. All rights reserved.

Introduction Cancer treatment has long focused on patient outcomes related to overall survival, relapse rates, and treatment response rate (ie, partial response, complete response). Traditional cancer treatment includes surgery, radiation, and/or chemotherapy. Over time, as these treatments have improved, quality of life after cancer treatment has received increased attention. Cancer survivors may struggle with persistent impairments even when the cancer is treated: nearly one in four cancer survivors experience poor health, compared with one in 10 in a cancer-free population cohort.1 A large study of Australian cancer survivors demonstrated that psychological distress among survivors is related more to physical disability than to the diagnosis of the cancer itself.2 Prehabilitation protocols are designed to improve patient functional and psychological well-being, and may offer a solution to the widespread issue of decreased functional health after cancer treatment. The principal tenet of prehabilitation holds that patients who are stronger with more endurance before cancer treatment will fare better after surgery, radiation, or chemotherapy than those with poor functional status. Cancer prehabilitation is defined as “identifying impairments and offering exercises aimed at strengthening and stabilizing potential at-risk organ systems prior to this treatment.” 3 Prehabilitation may prevent or decrease complications. Prehabilitation can also improve patients’ functional status to an acceptable level to * Address correspondence to: Alexander Lukez, BS, University of Massachusetts Medical School, 55 Lake Ave., Worcester, MA 01605 E-mail address: [email protected] (A. Lukez). https://doi.org/10.1016/j.soncn.2019.150976 0749-2081/© 2019 Elsevier Inc. All rights reserved.

allow for treatment or surgery. For example, lung cancer surgery can often only be tolerated by patients who can achieve a certain level of performance on pulmonary function tests. Aerobic training can improve pulmonary function tests, and thus broaden treatment options to include surgery. Prehabilitation affects clinical practice by improving patient outcomes such as functional status and quality of life. Furthermore, patients diagnosed with cancer experience distress in both the physical and psychological dimension. Male cancer patients cited “limitations in everyday activities” and female patients cited “anxiety/ worries” regarding areas of greatest concern.4 Often, a waiting period is required for testing or treatment after diagnosis. Offering an action plan, including a treatment plan with lifestyle modifications (exercise implementation, dietary modification), affords an opportunity for the patient to improve functional status while waiting to begin cancer treatment. Cancer prehabilitation can provide an actionable regimen for patients experiencing distress and who wish to preserve their ability to engage in premorbid activities after cancer treatment. Prehabilitation research is increasing at an exciting pace. On the NCBI PubMed database, a search query for “cancer prehab” produced two results in March 20133 and produced 17 results in June 2019. Likewise, “cancer prehabilitation” resulted in six items in March 20133 and 169 items in June 2019. The goal of this article is to present the current best evidence about the role and scope of prehabilitation in the cancer treatment trajectory. We provide an overview of the efficacy and benefits of prehabilitation in different cancer survivor populations and of the two major prehabilitation approaches, unimodal and multimodal regimens.

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Table 1 Sample prehabilitation interventions associated with benefits and reasonable measurements to determine the utility of such an intervention. Potential Benefit

Objective Measurement

Feasible Intervention

Functional status

6MWD, measurement of lung volume, respiratory maximal muscle strength, BMI, postoperative length of hospitalization, oxygen saturation, forced expiratory volume, urinary continence, ADL, instrumental ADL, Functional Assessment of Cancer Therapy SF-36 system, patient survey HADS, PHQ-9, GAD-7

Exercise regimen (aerobic conditioning, strength training), stretching regimen (flexibility training), balance training, breathing training for breath control and cough technique

Quality of life Mental health Postoperative complications

Clavien-Dindo classification, postoperative length of hospitalization, health care costs

Reduced misconceptions regarding operation/treatment Patient-physician partnership

Patient interview

Smoking cessation counseling, exercise regimen Stress management techniques, cognitive behavioral intervention Inspiratory spirometry exercises before lung surgery, aerobic and strength exercises before orthopedic surgery, chest physiotherapy Nurse counseling

Patient questionnaire

Prehabilitation (any form)

Abbreviations: 6MWD, 6-minute walking distance; BMI, body mass index; ADL, activities of daily living; HADS, hospital anxiety and depression score; PHQ-9, Patient Health Questionnaire; GAD-7, Generalized Anxiety Disorder 7-item scale.

A unimodal regimen consists of exercise only and multimodal regimens include a combination of targeted and conditioning exercise programs, nutritional and psychological interventions, and health behaviors (such as smoking cessation). Of the two approaches, experts endorse the multimodal approach, while acknowledging that barriers to access exist. One such barrier is timeliness in cancer diagnosis and treatment. A 2015 systematic review validated the association of superior outcomes afforded specific cancers (breast, colorectal, head and neck (H+N), testicular, and melanoma) treated in a prompt manner.5 Table 1 depicts the various benefits (eg, quality of life) associated with specific prehabilitation regimens.6 8 Importantly, prehabilitation has the potential to improve function and quality of life in cancer survivors. Unimodal Prehabilitation Regimens in Cancer Survivor Populations The unimodal regimen consists of one intervention only and predates most multimodal regimens. Studies exist for a variety of sites of malignancy, including gastrointestinal, lung, prostate, breast, gynecologic, and H+N cancers. Potential benefits of prehabilitation are summarized in Table 2.9 21 Gastrointestinal cancers In the United States, the 5-year survival for colorectal cancer (CRC) is 65%.9 Great emphasis is placed on appropriate screening and management of identified CRC.10 Further study on the dose and timing of prehabilitation may benefit a large population of patients undergoing treatment of CRC.11 A study of patients requiring colorectal resection, not limited to cancer patients, demonstrated the use of unimodal prehabilitation in the form of aerobic exercise.12 A 4-week course of prehabilitation was completed by patients in the exercise cohort, control group patients received no exercise.12 The exercise cohort was given a portable cycle ergometer for home use. Results demonstrated a significant increase in heart rate, oxygen uptake, and peak power output in the intervention group.12 A study published 1 year later was limited to patients undergoing abdominal surgery for resection of cancer.13 This randomized controlled trial included 42 patients who received either prehabilitation in an outpatient setting (cycling intervention) or home-based exercise advice (control group). The prehabilitation group had increased respiratory muscle endurance, while there was no difference in quality-of-life measures. Prehabilitation cycling intervention before resection surgery also improves aerobic parameters in cancer patients with liver metastases.14 This study randomized patients to exercise intervention or control with exercise three times weekly

over 4 weeks. Results of this study showed prehabilitation increased oxygen uptake, peak exercise, and improved quality of life.14 Endurance is likely related to chemotherapy tolerance,15 and unimodal prehabilitation with cycling has great promise in neoadjuvant therapy. A 2015 study investigated rectal cancer surgery patients while undergoing neoadjuvant chemoradiation.16 Researchers looked at oxygen uptake and lactate threshold in patients exercising in a 6-week structured training program versus controls. The intervention group exercised on a bike three times weekly. The authors found significant improvement in oxygen uptake and lactate threshold at 6 weeks in the exercise group as compared with the control group. Unimodal prehabilitation likely affects both muscle mass and strength, but not necessarily over the same time course. One study evaluated a population of patients with rectal cancer during a 10week course of aerobic and resistance exercise twice weekly during neoadjuvant chemoradiation.17 Results showed the expected loss of skeletal muscle mass from treatment, but an increase in leg press and leg extension strength despite this loss. Subjects improved 6-minute walking distance (6MWD). A pilot study published in addition of 2011 demonstrated improvement in cardiorespiratory fitness and muscle strength for 15 patients with abdominal and thoracic cancer undergoing prehabilitation for half the time as the rectal cancer patients.18 Benefits of prehabilitation in that study included improved aerobic capacity and functional strength.18 Among all abdominal cancers, pancreatic cancer has the poorest prognosis, often discovered in an advanced, unresectable stage (80% to 85% of cases).19 Only 4% of patients live more than 5 years after diagnosis.19 In patients with pancreatic cancer, prehabilitation may improve functional status and quality of life. Patients with pancreatic cancer were asked to complete 1 hour a week of moderate-intensity aerobic exercise as well as 1 hour a week of strengthening exercises before and during treatment.20 Patients completed over 2 hours a week of aerobic exercise on average and less than 40 minutes a week of strengthening exercises.20 The authors of this study concluded that while the aerobic exercises are easily accomplished, additional support is necessary for patients to participate in strength training, even when they are given equipment.20

Lung cancer Lung cancer is the most common cause of cancer-related death, and the most preventable.21 Lung cancer is often related to smoking.2 Smoking cessation has both short- and long-term benefits, and oncology nurses can assist patients with cessation.22 Often, patients with lung cancer have chronic obstructive pulmonary disease, increasing both the risk and subsequently the rewards of exercise.

Table 2 Efficacy of prehabilitation by cancer site. Methodology and Intervention

Results

Conclusions

Colorectal

Curtis et al, 201864

Comparison of patient length of time from diagnosis to treatment using overall survival as a primary endpoint

No significant difference in patients waiting 4, 8, or 12 weeks for treatment

Dimeo et al, 200315

Endurance and strength training, high-protein nutrition, smoking cessation, psychological support

Alejo et al, 201988

Pilot study of rectal cancer patients requiring neoadjuvant chemoradiation with program of exercises. Results measured by adherence, mental health inventory, BMI, physical fitness, and physical activity level observation Data from 185 patients compares those completing trimodal prehabilitation before colorectal cancer surgery Prehabilitation for patients undergoing radical prostatectomy, measuring the primary endpoint of physical activity level post-surgery and length of hospitalization NSCLC patients undergoing lobectomy and cardiopulmonary exercise testing with or without prehabilitation COPD patients undergoing lobectomy performed 2 weeks of pulmonary exercise and chest physiotherapy and were compared with historical controls (COPD patients undergoing lobectomy with usual care) Breast cancer patients were assigned to in-person or video education sessions for prehabilitation with measured outcomes of exercise compliance, shoulder pain, shoulder abduction ROM, and seroma formation

86% of patients recovered to baseline function 4 weeks postop compared with 40% in control (P < .01), no adverse events occurred Improvement in peak oxygen uptake (P < .05), reduced depression score (P < .05), and improved ‘emotional function’ in quality-of-life measurements (P < .05)

Prehabilitation may represent a safe option for patients who are newly diagnosed without increasing risk of mortality associated with treatment delay Prehabilitation efficacy was demonstrated in this study and led to an ongoing international randomized control trial Functional status and mental health may benefit rectal cancer patients requiring chemoradiation treatment

Minnella et al, 201756 28

Prostate

Au et al, 2019

Lung

Gravier et al, 201989 Sekine et al, 200590

Breast

Baima et al, 201731

Rao et al, 200932

Pancreatic

Parker et al, 201920

Nakajima et al, 201946

Urologic

Cottam et al, 201876

Gynecologic

Carli et al, 201272

98 breast cancer patients were assigned to yoga or supportive therapy prior to treatment. Yoga was 60 minutes daily. Supportive therapy was a routine part of hospital visit. Assessments included Speilberger’s State Trait Anxiety Inventory and symptom checklist Preoperative pancreatic cancer patients were advised 60 min/week moderate-intensity aerobic exercise and 60 min/week full-body strengthening exercises concurrent with cancer treatment, self-reported aerobic and strengthening minutes were measured, as were objective measurements with accelerometers Patients requiring an open abdominal surgery for HPB malignancy underwent prehabilitation and were compared with historical controls Case report investigated prehabilitation in bladder transitional cell carcinoma prior to cystectomy using multimodal prehabilitation (nutritional counseling, respiratory muscle training, and supervised cycle ergometer interval training) Case study of in endometrial cancer patient tested a 3week prehabilitation program of strength and endurance exercise and nutritional optimization before a total abdominal hysterectomy

Prehabilitation group had better 6MWD at both time points (4 and 8 weeks) with significance (P < .001) Prehabilitation cohort had statistically significant more activity at 1 day and 1 week post-surgery and no difference in time of hospitalization Patients with prehabilitation experienced fewer complications (P < .05) Postop stay was longer in the non-prehabilitation group and the ratio of postop to predicted postop FEV1 was significantly better in the prehabilitation cohort

Multimodal prehabilitation improves walking capacity throughout the perioperative period There was no difference in the length of hospitalization; however, postop increase in exercise capacity may indicate a benefit in acute morbidity Prehabilitation benefits patients undergoing lobectomy by decreasing postop complications Decrease in length of hospitalization may be achieved for COPD patients requiring lobectomy

No difference in exercise compliance between in-person and video teaching, two thirds of patients lost more than 10° of shoulder abduction ROM 1 month after surgery, 15% of patients had worse shoulder pain 3 months after surgery, no increased risk of seroma formation Decrease in self-reported and trait anxiety in the yoga group compared with the supportive therapy group

Study demonstrated the feasibility of prehabilitation in breast cancer patients and similar levels of compliance between method of teaching (in-person or video)

Patients reported an average of 126 minutes of aerobic exercise and an average of 39 minutes of strengthening exercises, patients measured an average of 158 min/week of accelerometer-detected moderate or greater exercise

Preoperative aerobic and strengthening exercises are feasible; however, encouragement and support may be necessary when prescribing strengthening exercises

Serum albumin levels were more likely to be abnormal in the non-prehabilitation cohort, prehabilitation cohort had improved 6MWD and total muscle/fat ratio, postop stay was shorter in the prehabilitation cohort Weight loss, improved FVC, FEV1, and PEF, increased minute ventilation, and a reduced 30-day mortality calculation

Benefits in functional status and length of hospitalization indicate significant benefit for prehabilitation in the HPB cancer patient population

No postop confusion after prehabilitation, with sustained improvement in exercise tolerance, cognitive function, and functional capacity

Further research is necessary to determine the role of prehabilitation in endometrial cancers

Yoga may be used for managing anxiety in breast cancer outpatients

There is a potential role for prehabilitation in urologic cancers

Abbreviations: BMI, body mass index; postop, postoperative; 6MWD, 6-minute walking distance; NSCLC, non small cell lung cancer; COPD, chronic obstructive pulmonary disease; ROM, range of motion; HPB, hepatopancreatoduodenectomy.

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Author

A. Lukez and J. Baima / Seminars in Oncology Nursing 00 (2019) 150976

Primary Site of Cancer

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A landmark study in patients with chronic obstructive pulmonary disease undergoing lung resection randomized subjects to inspiratory muscle training and incentive spirometry before and after resection or no training.23 The intervention group demonstrated significant improvements on pulmonary function tests.23 This is particularly important because this population may be excluded from surgical treatment for poor preoperative performance on pulmonary function tests.24 Improvements in pulmonary function after 4 weeks of aerobic and breathing exercise were demonstrated in patients with lung cancer who were previously excluded from surgery because of poor performance.23 A meta-analysis of 15 studies included 350 patients undergoing exercise prehabilitation before resection for lung malignancy.25 Prehabilitation decreased the risk of pulmonary complications, decreased number of days requiring an intercostal catheter, decreased postoperative length of hospitalization, and improved measures of functional status such as 6MWD and pulmonary function parameters.25 Prostate cancer Although prostate cancer accounts for one in five new cancer diagnoses, 5-year survival is the highest at 99%.26 Because of the potential for urinary dysfunction, pelvic floor exercises were the primary outcome measure for early focused exercise in this population.27 Although these techniques can be taught before surgery, the exercises themselves are not typically preformed until after. Unimodal prehabilitation with whole-body exercise was later investigated by researchers who analyzed perioperative physical activity by accelerometer.28 Primary endpoints for this study included the level of physical activity in the immediate post-surgery period and the length of hospitalization following surgery.28 Patients randomized to the prehabilitation cohort had 4 to 8 weeks of aerobic and resistance exercise before surgery.28 Prior to surgery, this group demonstrated less anxiety and decreased body fat than controls. The intervention group performed more activity in the inpatient setting, while there was no difference found between the groups in the outpatient setting.28 At 4 weeks after surgery, the intervention group had significantly greater 6MWD, linking physical activity with quicker recovery of endurance.28 Breast cancer Thirty percent of all new cancer diagnoses in women are attributable to breast cancer, and 5-year survival is 90%.26 The authors of a meta-analysis of 33 trials concluded that exercise is beneficial in this population, in both physical health and mental health domains.29 Many patients with breast cancer exhibit loss of shoulder range of motion after surgery.30 Unimodal prehabilitation has been investigated in this population for upper quarter dysfunction31 and anxiety.32 A 2017 study evaluated the feasibility of unimodal prehabilitation. Researchers taught study participants three exercises in-person for shoulder range of motion and offered them both a written description and a link to watch a video.3 There was no significant difference in exercise compliance between patients using the video or the written description.3 There was no difference in risk of seroma formation after surgery between the exercising and non-exercising cohort. As expected, shoulder range of motion decreased after surgery, but insufficient follow-up was available to establish if exercisers recovered shoulder range of motion more quickly.3 Mental health is another target for unimodal prehabilitation in patients with breast cancer. A group of patients was randomized to yoga or routine supportive care before their treatment.32 The intervention continued throughout surgery, adjuvant radiotherapy, and chemotherapy.32 The exercise cohort demonstrated less anxiety as compared with controls after surgery, as well as during radiotherapy and chemotherapy.32 Novel research is underway investigating the mechanism of unimodal prehabilitation in breast cancer tissue. One study evaluated patients

with stage I III breast cancer before surgery and intervention of either exercise or mind-body control.33 Exercise intervention patients had a decrease in serum leptin and IGF-that was not present in controls.33 Further analysis found 13 unique pathways upregulated in the exercise cohort, most significant was the cytokine-cytokine receptor interaction.34 Likewise, 13 pathways were downregulated in the exercise cohort, with the most significant downregulation in RNA transport and DNA replication.34 There were no changes noted in pathways for the control cohort.34 These findings suggest metabolic and genetic pathways for the protective effects of presurgical exercise in breast cancer. Gynecologic cancers The incidence of uterine cancer continues to increase in the United States26 and obesity is a known independent risk factor,35 rendering exercise an attractive intervention. Unimodal exercise in the form of aerobic and strengthening exercise was offered to a cohort of patients awaiting endometrial surgery in the less than 2 weeks (average, 12.5 days) before surgical resection.36 Participants demonstrated improved fitness-related quality of life and decreased waist circumference, as well as decreased anxiety and depression.36 There was no change in lung function or body mass index.36 Results are promising for exercise interventions in this population. Head and neck cancers Five-year survival of cancer of the oral cavity and pharynx is 65%.26 Treatment involves surgery, chemotherapy, and radiation. H+N malignancies may affect structures crucial for speech, mastication, and swallowing.37 Voice and speech changes are common after concurrent chemotherapy. A study in advanced H+N cancers revealed voice and speech changes peak at 10 weeks and level off 1 year after treatment.38 A 2018 study queried H+N cancer patients regarding their exercise preferences; 437 patients responded, and a frequency of 3 times a week for less than 30 minutes per session was the most preferred regimen.39 Preliminary results from a program of swallowing and mouth opening exercises along with progressive resistance training during radiotherapy for H+N cancer showed exercise of the oropharynx is feasible during treatment.40 More recent data from this study showed median adherence of 78% to 3-times-weekly sessions of 30 minutes.41 As such, multiple short duration sessions may be the best approach for unimodal prehabilitation in this population. In summary, unimodal prehabilitation benefits newly diagnosed cancer patients by improving functional status and minimizing toxicities related to treatment. Unimodal cancer prehabilitation patients may benefit psychosocially. Further, unimodal prehabilitation may be associated with reductions in health resource use and costs. The following case example illustrates the typical implementation, goals, and outcomes of unimodal prehabilitation and a patient with breast cancer. Case example A 73-year-old woman with a history of chronic left shoulder osteoarthritis, lumbar stenosis, and thoracic compression fracture was diagnosed with a well-differentiated invasive ductal carcinoma in the upper outer quadrant of left breast, less than 1 cm in size. Her left anterior shoulder pain had been managed with naproxen and aspirin. Her pain was worse with reaching and better with rest. Although she found physical therapy helpful for her lumbar stenosis, she had not found helpful exercises for her shoulder. Functionally, she was independent in all activities of daily living. She was referred to physiatry by her oncology nurse navigator prior to surgery after multidisciplinary tumor board recommendations for lumpectomy with possible axillary node dissection. At the time of initial physical exam, inspection of the trunk and upper limbs revealed no focal atrophy or rashes. There was no palpable cervical lymphadenopathy. There was tenderness of the left subacromial

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bursa. Spurling’s test was negative, suggesting the absence of cervical radiculopathy. There was a painful arc on the left. Strength was normal and symmetric in the upper limbs throughout; however, the patient reported 6/10 pain with resisted shoulder abduction and external rotation. Abduction range of motion was 120°on the right and 110°on the left. The patient was prescribed an independent daily exercise regimen of three shoulder range-of-motion exercises at home until her scheduled lumpectomy (2.5 weeks after beginning the exercises) and recommended to resume the exercises when comfortable after discharge. While hospitalized for surgery, she stopped these exercises. She received postoperative care education including range of motion limitations from her nurse. She spent the first 2 days keeping her arm at shoulder height or below while upright and gradually began increasing her range of motion, first supine and then upright. The operation consisted of left breast lumpectomy with sentinel lymph node biopsy. The patient tolerated the procedure well. She reported performing two of the three exercises as instructed. One month post-surgery, the patient rated her shoulder pain as 0/10. Physical exam revealed no loss in range of motion in flexion and abduction of the left and right shoulders. The patient reported intermittent joint pain that started only after tamoxifen use, which was manageable with NSAIDs. Multimodal Prehabilitation Regimens in Cancer Survivor Populations Multimodal prehabilitation can include targeted or whole-body exercise, nutrition, psychologic support, education, and smoking cessation, or any combination of these components. Many experts endorse this as the preferred form of prehabilitation when available.42 Targeted or focused exercise generally involves the use of stretching and strengthening to treat or prevent muscle/joint impairment, such as shoulder range of motion exercises before axillary node dissection in breast cancer.43 Whole-body exercise is for general deconditioning, such as walking for patients with lung cancer. Whole-body exercise can also include strengthening, which is often perceived as the most challenging component of prehabilitation.44 Patients with any type of cancer could have musculoskeletal impairments that affect their function or suffer general deconditioning from surgery, chemotherapy, or radiation.45 Exercise without adequate nutrition may be ineffective because protein is essential for exercise, regardless of the timing. Prehabilitation is sometimes measured as the absence of an expected loss. For example, albumin typically goes down after gastrointestinal surgery. One study of cancer patients undergoing prehabilitation for hepatopancreatobiliary resection did not lose albumin after surgery as compared with a control group.46 Isolated nutrition interventions are hard to assess because dietetic intervention is so frequently coupled with exercise. With isolated intervention, nutritional outcomes and symptoms improved with an average 34-day preoperative intervention period in patients with hepatopancreaticobiliary cancer.47 Another study comparing whey protein supplementation with placebo during the same 4 weeks of exercise for both groups before colorectal surgery found clinically meaningful changes in aerobic capacity in the intervention group.48 As with other domains, the majority of what is known about the psychologic component of prehabilitation comes from patients with breast cancer. Anxiety and depression are common throughout the cancer care trajectory.49 Interventions to decrease stress before surgery may decrease cortisol, enhance wound healing, and improve the immune response.48 Delivery typically involves one or two sessions in the 14 days (or less) before surgery.48 One review of seven studies concluded no effect on length of stay, but gains in immune function and quality of life.48 Measurement tools for mental health outcomes may be more helpful to measure isolated psychologic prehabilitation.

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With front line access to patients, nurses have a vital role in the education component of prehabilitation.50 In orthopedic surgery, preoperative patient education enhances patient knowledge.51 Written material is helpful, but should be used along with verbal instruction.50 Although the individual role of education in cancer prehabilitation has not been fully investigated, early assessments of physical and mental health provided by nursing are crucial in effective execution of perioperative education.52 In surgical patients, smoking cessation has been shown to restore the tissue microenvironment through improved tissue oxygenation.53 Cigarette smoke induces cytochrome p450 and its isoforms, which accelerates drug clearance and may narrow the therapeutic index of chemotherapy.54 Smoking cessation may not only improve postoperative outcomes, but offer a lower risk of future cancer or cardiovascular disease. Gastrointestinal cancers Multimodal programs, typically in the form of exercise, nutrition, and psychological prehabilitation, have been best investigated in the CRC population. Patients with CRC who underwent 1 month of trimodal prehabilitation delivered by professionals in the three domains (kinesiologist, dietician, psychologist) demonstrated improved 6MWD and faster functional recovery to baseline than controls.55 Analysis of this study, along with two others conducted over 5 years at the same institution, yields confirmation that trimodal prehabilitation produces consistently quicker recovery in patients with CRC, even when intervention subjects are older.56 Combined compliance for all three studies was 70% to 98% with no adverse events, suggesting safety and feasibility. Of note, an earlier study conducted by this group had an intervention compliance of 16%,57 presumably because the intervention was too hard, suggesting that the exercise should be carefully tailored to the at-risk population.58 Less is known about multimodal prehabilitation in other gastrointestinal cancers. A randomized controlled trial of patients who had exercise and nutrition prehabilitation before esophageal or gastric cancer surgery showed improvements in 6MWD as compared with controls.59 A study of patients with any hepatopancreatobiliary malignancy also used the combination of exercise and nutrition prehabilitation. Researchers found not only improved physical fitness and lack of nutritional decline, but a decrease in length of hospitalization in the prehabilitation group.60 Gastrointestinal prehabilitation is likely a dose-dependent phenomenon. In one study, patients awaiting gastrointestinal cancer surgery averaged 5.7 training sessions in the 2 weeks prior to surgery.61 Although inspiratory muscle function improved significantly, there was no benefit in aerobic capacity or peripheral muscle strength. In contrast, a 4-week trimodal prehabilitation program in patients with CRC improved aerobic capacity in the form of 6MWD.62 This program involved supervised aerobic and strength training exercise with a kinesiologist. Addition of a once-weekly supervised exercise session to this established program did not enhance outcomes.63 Four weeks of prehabilitation is likely feasible in the CRC population, especially those undergoing laparoscopic surgery.64 An international trimodal CRC surgery prehabilitation study is currently underway to quantify the potential health and cost benefits.65 Lung cancer Although nutrition is a concern in all cancer patients, protein supplementation may have a more measurable functional benefit in patients with gastrointestinal cancer than in those with lung cancer. Theoretically, smoking cessation is a better target in this population. However, a published analysis of smoking cessation prehabilitation failed to show conclusive benefit.66 One theory for this is that 4 weeks of cessation is needed before surgery to show benefit, and most studies had a shorter

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period. Also, very few studies focused on smoking cessation as an isolated component of prehabilitation. Increasing the availability of lung cancer screening in smokers may change the landscape of smoking cessation prehabilitation.67 In terms of available data on successful lung cancer prehabilitation, 2 to 6 weeks of high-intensity interval training is currently recommended as an important component.68

prehabilitation entailed nutritional counseling, respiratory muscle training, and supervised cycle ergometer interval training. The patient achieved weight loss, improved lung function, and a reduced 30-day mortality (11.5% to 6.5%) calculation.76 The authors of this study have plans to execute a structured prehabilitation plan for high-risk surgical patients.

Prostate cancer

Head and neck cancers

Many patients with lung cancer will quit smoking with the cancer diagnosis. Behavior change does not follow a similar pattern in prostate cancer. A qualitative analysis of motivation to exercise was carried out in prostate cancer survivors undergoing 12 weeks of supervised exercise in the form of team European football.69 Subjects cited access to health care professionals and accountability as drivers for exercise.66 This may mean that, for some cancers, group prehabilitation is appropriate. Prehabilitation in prostate cancer may also include a psychologic component. One study in patients with prostate cancer revealed stress management resulted not only in lower levels of mood disturbance, but also improved immune parameters.70 Efficient delivery of multimodal prehabilitation in prostate cancer has not been investigated, but likely requires a different approach because impairments and established patient preferences differ from other cancers.

Like urologic surgery, studies are primarily in postsurgical rehabilitation because impairments are varied and may be difficult to assess before treatment. Smaller and harder-to-access pelvic and H+N (axial) musculature complicates assessment of improvement. Lymphedema can be seen in H+N patients and may affect articulation and swallowing.77 A prehabilitation intervention program in H+N patients improved detection of external lymphedema.77 These authors point out that a dedicated nurse navigator is essential for the success of their intervention for lymphedema.77 In summary, multimodal cancer prehabilitation includes exercise, nutrition, psychologic support, education, and smoking cessation as means of improving functional status and recovery from treatment. The combined impact of multimodal intervention may maximize the benefits for patients preparing for cancer treatment. There is a need for further study into the appropriate interdisciplinary utilization prehabilitation to derive maximum benefit for patient health, quality of life, and recovery.

Breast cancer Multimodal prehabilitation with total body exercise, targeted exercise, nutrition, psychologic aid, and smoking cessation is recommended in breast cancer because surgery, chemotherapy, and radiation can affect all body systems.43 However, barriers to multimodal prehabilitation exist, even in such a common cancer. Aggressive treatment may leave little time for prehabilitation, and the use of combined modalities complicates scheduling a multimodal intervention. Effective prehabilitation has not been established in this population, but results are promising for its application, especially in terms of the targeted and whole-body exercise components.71 Gynecologic cancers Currently, gynecology prehabilitation is limited to case reports and smaller studies. An 88-year-old woman with endometrial cancer performed a 3-week multimodal prehabilitation program of strength and endurance exercise and nutritional optimization before a total abdominal hysterectomy.72 Despite prior episodes of delirium in the hospital, she was found to have no postoperative confusion. She demonstrated improvement in exercise tolerance, cognitive function, and functional capacity throughout the study period. A review of five available studies, including this case report, pointed out the relative scarcity of data.73 Timing ranges from one preoperative session to 6 months prior to surgery. The authors explain that surgery is no longer always the best treatment strategy for gynecologic cancer, which may result in heterogeneous programs to accommodate the different treatments. Overall, recommendation is in favor of prehabilitation because most treatments will require a wait time and elevated BMI is a known risk factor for both gynecologic malignancy and poor perioperative performance. There is further investigation ongoing into the role of prehabilitation in the context of gynecologic cancers.74 Future directions for study in gynecological malignancies may include prehabilitation for radiation therapy.75 Urologic cancers Studies on urinary dysfunction in cancer are largely focused on the prostate cancer population,27 likely because of prevalence. A case report presented in 2018 investigated prehabilitation in a man with bladder transitional cell carcinoma prior to cystectomy.76 Multimodal

Barriers to implementation A cohort of lung and CRC patients preferred home-based prehabilitation in the form of one supervised session a week.4 They did enjoy the supervised sessions, but the biggest barrier to their consistent participation was transportation.4 Transportation and cost are consistent barriers to exercise participation in patients with breast cancer.78 Home-based prehabilitation has been successfully executed in patients with pancreatic cancer, and this may serve as a model for other cancers.79 The heterogeneity of available timing and programs is not unlike the heterogeneity of types and treatments for cancer. Likely, rapid treatment is more crucial in some cancers than others. For example, time from CRC diagnosis to curative laparoscopic surgery did not affect outcomes in 673 patients with CRC in the United Kingdom.80 Mean time to surgery was 53 days. In a smaller group of patients with non small cell lung cancer, there was no significant effect of delay in surgical intervention on prognosis. Median time to surgery was 82 days.81 Timing varies widely across locations, as one US study reported time from diagnosis to initial treatment in lung cancer at 15 days.82 Because as little as 1 week of prehabilitation may make a difference,83 we recommend proceeding with treatment as soon as possible but offering prehabilitation even when there is only a short window. Supervision is a preferred component, and future directions could include electronic supervision. A study is underway to evaluate multimodal prehabilitation delivered over telehealth.84 Role of the Oncology Nurse The role of the oncology nurse is broad and multidisciplinary collaboration is a key component. Nurses participate in cancer prehabilitation by performing functional assessments, documenting status changes, providing education to patients and other providers, and performing or connecting patients to available unimodal or multimodal prehabilitation.85 Nurse navigators in particular may be the only consistent provider the patient sees throughout surgery, chemotherapy, and/or radiation treatments.86 The cancer care continuum is exceedingly complex, and the addition of a nurse navigator has been shown to not only improve patient satisfaction, but also shorten time

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to treatment.82 Although surgery, chemotherapy, and radiation are the traditional cancer treatments, exercise is quickly becoming an integral part of the tolerance and even success of those treatments.87 Connecting patients to prehabilitation early in the cancer care spectrum through oncology nursing shows great promise. Conclusion Cancer prehabilitation presents an opportunity to improve patient quality of life in preparation for intensive treatments involving surgery, chemotherapy, and radiation. Exercise may be offered in both unimodal and multimodal regimens, with multimodal regimens including nutrition, psychological intervention, education, and smoking cessation. Benefits include improved functional status, better quality of life, reduced morbidity, improved mental well-being, and reduced health care expenditures. 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