Research Priorities in Prehabilitation for Patients Undergoing Cancer Surgery: An International Delphi Study.

BACKGROUND: Recently, the number of prehabilitation trials has increased significantly. The identification of key research priorities is vital in guiding future research directions. Thus, the aim of this collaborative study was to define key research priorities in prehabilitation for patients undergoing cancer surgery. METHODS: The Delphi methodology was implemented over three rounds of surveys distributed to prehabilitation experts from across multiple specialties, tumour streams and countries via a secure online platform. In the first round, participants were asked to provide baseline demographics and to identify five top prehabilitation research priorities. In successive rounds, participants were asked to rank research priorities on a 5-point Likert scale. Consensus was considered if > 70% of participants indicated agreement on each research priority. RESULTS: A total of 165 prehabilitation experts participated, including medical doctors, physiotherapists, dieticians, nurses, and academics across four continents. The first round identified 446 research priorities, collated within 75 unique research questions. Over two successive rounds, a list of 10 research priorities reached international consensus of importance. These included the efficacy of prehabilitation on varied postoperative outcomes, benefit to specific patient groups, ideal programme composition, cost efficacy, enhancing compliance and adherence, effect during neoadjuvant therapies, and modes of delivery. CONCLUSIONS: This collaborative international study identified the top 10 research priorities in prehabilitation for patients undergoing cancer surgery. The identified priorities inform research strategies, provide future directions for prehabilitation research, support resource allocation and enhance the prehabilitation evidence base in cancer patients undergoing surgery.

Preoperative cardiopulmonary exercise testing improves risk assessment of morbidity and length of stay following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the standard treatment for selected patients with peritoneal malignancy. The optimal means of assessing risk prior to these complex operations is not known. This study explored the associations between preoperative cardiopulmonary exercise testing (CPET) variables and postoperative outcomes following elective CRS and HIPEC. This study included patients who underwent routine preoperative CPET prior to elective CRS and HIPEC at Royal Prince Alfred Hospital in Sydney between July 2017 and July 2020. CPET was performed using a cycle ergometer and measured peak oxygen uptake (VO2 peak) and anaerobic threshold (AT). Outcomes included in-hospital morbidity, length of intensive care unit (ICU) stay and hospital stay. The associations between preoperative CPET variables and postoperative morbidity were assessed using univariate and multivariate analyses. A total of 129 patients were included. Mean age was 56 years (standard deviation (SD) 12.5 years), and colorectal cancer was the most common indication for CRS and HIPEC. The overall complication rate was 69%, and two (1.6%) patients died in hospital. Patients who did not develop any postoperative complication had slightly higher preoperative AT and VO2 peak and shorter length of hospital stay. Data in this study support the role of CPET prior to CRS and HIPEC as an adjunct to improve risk assessment.

Validation of a risk prediction calculator in Australian patients undergoing head and neck microsurgery reconstruction.

BACKGROUND: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) surgical risk calculator (SRC) is an open access calculator predicting patients' risk of postoperative complications. This study aims to assess the validity of the SRC in patients undergoing microsurgical free flap reconstruction at an Australian tertiary referral centre. METHODS: This is a retrospective cohort study of 200 consecutive patients treated up to November 2020. SRC-predicted rates of postoperative complications and hospital length of stay (LOS) were compared to those observed for the ablative and reconstructive components of the procedure. The performance of the SRC was assessed using Brier scores, area under the receiver operating characteristic (ROC) curve (AUC), and the Hosmer-Lemeshow test. RESULTS: For both ablative and reconstructive components, the SRC discriminates well for pneumonia and urinary tract infection, and it is calibrated well for readmission and sepsis, but it does not discriminate and calibrate well for any single outcome. SRC-predicted hospital LOS and actual LOS did not correlate well for the reconstructive component, but they correlated strongly for the ablative component. CONCLUSIONS: The SRC is a poor predictor of postoperative complication rates and hospital LOS in patients undergoing head and neck microsurgical reconstruction.

PRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL).

BACKGROUND: Radical surgery is the mainstream treatment for patients presenting with advanced primary or recurrent gastrointestinal cancers; however, the rate of postoperative complications is exceptionally high. The current evidence suggests that improving patients' fitness during the preoperative period may enhance postoperative recovery. Thus, the primary aim of this study is to establish the effectiveness of prehabilitation with a progressive, individualised, preoperative exercise and education program compared to usual care alone in reducing the proportion of patients with postoperative in-hospital complications. The secondary aims are to investigate the effectiveness of the preoperative intervention on reducing the length of intensive care unit and hospital stay, improving quality of life and morbidity, and reducing costs. METHODS: This is a multi-centre, assessor-blinded, pragmatic, comparative, randomised controlled trial. A total of 172 patients undergoing pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy will be recruited. Participants will be randomly allocated to prehabilitation with a preoperative exercise and education program (intervention group), delivered over 4 to 8 weeks before surgery by community physiotherapists/exercise physiologists, or usual care alone (control group). The intervention will comprise 12 to 24 individualised, progressive exercise sessions (including aerobic/anaerobic, resistance, and respiratory exercises), recommendations of home exercises (16 to 32 sessions), and daily incidental physical activity advice. Outcome measures will be collected at baseline, the week prior to surgery, during the hospital stay, and on the day of discharge from hospital, and 1 month and 1 months postoperatively. The primary outcome will be the development of in-hospital complications. Secondary outcomes include the length of intensive care unit and hospital stay, quality of life, postoperative morbidity and costs. DISCUSSION: The successful completion of this trial will provide robust and high-quality evidence on the efficacy of a preoperative community- and home-based exercise and education intervention on important postoperative outcomes of patients undergoing major gastrointestinal cancer surgery. TRIAL REGISTRATION: This trial was registered prospectively with the Australian New Zealand Clinical Trials Registry ( ACTRN12621000617864 ) on 24th May 2021.

Preoperative Cardiopulmonary Exercise Test Associated with Postoperative Outcomes in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analyses.

BACKGROUNDS: There is mixed evidence on the value of preoperative cardiorespiratory exercise test (CPET) to predict postoperative outcomes in patients undergoing a cancer surgical procedure. The purpose of this review was to investigate the association between preoperative CPET variables and postoperative complications, length of hospital stay, and quality of life in patients undergoing cancer surgery. METHODS: A search was conducted on MEDLINE, Embase, AMED, and Web of science from inception to April 2020. Cohort studies investigating the association between preoperative CPET variables, including peak oxygen uptake (peak VO2), anaerobic threshold (AT), or ventilatory equivalent for carbon dioxide (VE/VCO2), and postoperative outcomes (complications, length of stay, and quality of life) were included. Risk of bias was assessed using the QUIPS tool. A random-effect model meta-analysis was performed whenever possible. RESULTS: Fifty-two unique studies, including 10,030 patients were included. Overall, most studies were rated as having low risk of bias. Higher preoperative peak VO2 was associated with absence of postoperative complications (mean difference [MD]: 2.28; 95% confidence interval [CI]: 1.26-3.29) and no pulmonary complication (MD: 1.47; 95% CI: 0.49-2.45). Preoperative AT and VE/VCO2 also demonstrated some positive trends. None of the included studies reported a negative trend. CONCLUSIONS: This systematic review and meta-analysis demonstrated a significant association between superior preoperative CPET values, especially peak VO2, and better postoperative outcomes. The assessment of preoperative functional capacity in patients undergoing cancer surgery has the potential to facilitate treatment decision making.

Feasibility and acceptability of a preoperative exercise program for patients undergoing major cancer surgery: results from a pilot randomized controlled trial.

OBJECTIVE: To establish the feasibility and acceptability of a preoperative exercise program, and to obtain pilot data on the likely difference in key surgical outcomes to inform the sample size calculation for a full-scale trial. DESIGN: Pilot randomized controlled trial. SETTING: Royal Prince Alfred Hospital, Sydney, Australia. SUBJECTS: We included patients undergoing elective pelvic exenteration or cytoreductive surgery aged 18 to 80 years, who presented to the participating gastrointestinal surgeon at least 2 weeks prior to surgery. Patients presenting cognitive impairment, co-morbidity preventing participation in exercise, inadequate English language, currently participating in an exercise program or unable to attend the exercise program sessions were excluded. METHODS: Participants were randomized to a 2-6 weeks preoperative, face-to-face, individualised exercise program or to usual care. Feasibility was assessed with consent rates to the study, and for the intervention group, retention and adherence rates to the preoperative exercise program. Acceptability of the exercise program was assessed with a semi-structured questionnaire exploring the advice received and the amount, duration and intensity of the exercise program. In addition, postoperative complication rates (Clavien-Dindo), length of hospital stay and self-reported measures of health-related quality of life (SF-36v2) were collected at baseline, day before surgery and in-hospital up to discharge from hospital. RESULTS: Of 122 patients screened, 26 (21%) were eligible and 22 (85%) accepted to participate in the trial and were randomized to the intervention (11; 50%) or control group (11; 50%). The median age of the include participants was 63 years. Adherence to the preoperative exercise sessions was 92.7%, with all participants either satisfied (33%) or extremely satisfied (67%) with the overall design of the preoperative exercise program. No significant differences in outcomes were found between groups. CONCLUSIONS: The results of our pilot trial demonstrate that a preoperative exercise program is feasible and acceptable to patients undergoing major abdominal cancer surgery. There is an urgent need for a definite trial investigating the effectiveness of a preoperative exercise program on postoperative outcomes in patients undergoing major abdominal cancer surgery. This could potentially reduce postoperative complication rates, length of hospital stay and subsequently overall health care costs. TRIAL REGISTRATION: ACTRN12617001129370. Registered on August 1, 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373396&showOriginal=true&isReview=true.

The role of prehabilitation in frail surgical patients: A systematic review.

INTRODUCTION: Increasing emphasis is being placed on the detection of frailty in the pre-operative setting given its association with surgical morbidity and mortality. Prehabilitation seeks to increase the physiological reserve of frail patients, attenuating the risk of irreversible functional decline following surgery. AIM/HYPOTHESIS: This systematic review appraises the evidence available for prehabilitation in frail surgical patients. We proposed that exercise prehabilitation would especially benefit frail patients, with improvements in pre-operative functional capacity, and reductions in complications and length of hospital stay. METHODS: A literature search was conducted in MEDLINE, PubMed and CINAHL databases. Studies were included if they consisted of a prehabilitation intervention in frail patients undergoing surgery and specified a frailty model/index. Eight studies were included for analysis, 2 of which are ongoing studies. RESULTS: In 3 studies, prehabilitation consisted of an exercise intervention alone. There was a high feasibility of prehabilitation and a trend to improved pre-operative function, however, no evidence of improved post-operative functional recovery was there. In 2 studies, prehabilitation consisted of both exercise and nutritional interventions. Reductions in mortality and duration of hospital stay were reported, but the quality of evidence was judged to be very low. There was a lack of evidence of improved outcomes following pre-operative inspiratory muscle training in frail patients. DISCUSSION: This systematic review focuses on prehabilitation in frail surgical patients and reports that evidence supporting any outcome is limited, despite high feasibility and acceptability. There is a need for large randomised controlled trials to better establish the effects of prehabilitation in frail patients.

Feasibility and acceptability of PrE-operative Physical Activity to improve patient outcomes After major cancer surgery: study protocol for a pilot randomised controlled trial (PEPA Trial).

BACKGROUND: There is a need for evidence of the effectiveness of pre-operative exercise for patients undergoing major cancer surgery; however, recruitment to such trials can be challenging. The PrE-operative Physical Activity (PEPA) Trial will establish the feasibility and acceptability of a pre-operative exercise programme aimed to improve patient outcomes after cytoreductive surgery and pelvic exenteration. The secondary aim is to obtain pilot data on the likely difference in key outcomes (post-operative complications, length of hospital stay, post-operative functional capacity and quality of life) to inform the sample size calculation for the substantive randomised clinical trial. METHODS/DESIGN: Twenty patients undergoing cytoreductive surgery and pelvic exenteration at the Royal Prince Alfred Hospital, Sydney will be recruited and randomly allocated (1:1 ratio) to either 2 to 6 weeks' pre-operative exercise programme (intervention group) or usual care (control group). Those randomised to the intervention group will receive up to six individualised, 1-h physiotherapy sessions (including aerobic and endurance exercises, respiratory muscle exercises, stretching and flexibility exercises), home exercises (instruction and recommendations on how to progress the exercises at home) and encouragement to be more active by using an activity tracker to measure the number of steps walked daily. Patients allocated to the control group will not receive any specific advice about exercise training. Feasibility will be assessed with consent rates to the study, and for the intervention group, retention and adherence rates to the exercise programme. Acceptability of the exercise programme will be assessed with a semi-structured questionnaire. The following measures of the effectiveness of the intervention will be collected at baseline (2 to 6 weeks pre-operative), a week before surgery, during hospital stay and pre hospital discharge: post-operative complication rates (Clavien-Dindo), post-operative functional capacity (Six-minute Walk Test) and quality of life (SF-36v2®) and length of hospital stay. Functional status will be additionally measured using Cardiopulmonary Exercise Testing (CPET), at baseline and within a week before surgery. DISCUSSION: The PEPA Trial will provide important information about the feasibility and acceptability of a pre-operative exercise programme for patients undergoing major cancer surgery. Data from the PEPA Trial will be used to inform the design, methodology and to calculate sample size required for a larger, definitive trial. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12617001129370 . Registered on 1 August 2017.