PREHABILITATION AND POSTOPERATIVE BURDEN OF HIGH-RISK CANCER PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Introduction. Prehabilitation aims to optimize patients before surgical treatment in order to improve postsurgical recovery. While its efficacy to improve major postoperative clinical outcomes have been recognized for the broader low-risk surgical population, it remains unclear if the high-risk surgical population also benefits. This meta-analysis assessed the impact of prehabilitation on postoperative outcomes in high-risk surgical cancer patients
Methodology: We searched for experimental (randomized and non- randomized) and observational studies investigating the impact of prehabilitation in the frequency and/or severity (e.g minor and major complications) of post-surgical complications (primary outcome), type of complications, functional capacity, hospital readmissions, length of hospital stay and 30 day post-surgical mortality (secondary outcomes). High-risk patients for adverse surgical events were defined as frail and / or age ≥70 years and / or with an ASA score of >III.
Results: 136 articles were found, of which only 6 were eligible for qualitative and quantitative evaluation (3 randomized and 3 observational studies). The analysis resulted in a total of 674 participants, with an average age of 78 years, mostly male. Prehabilitation resulted in a lower risk of major complications (risk difference –0.09, 95% CI: –0.15, – 0.03, p = 0.005; i2 = 27%, p = 0.24) and surgical complications (RR 0.62, 95% CI 0.43 to 0.89, p=0.01; I2 = 33%, p = 0.22) in comparison to patients receiving standard care. Also, prehabilitation reduced the length of hospital stay (mean difference of – 2.7, 95% CI: –5.37 to –0.17, p = 0.04) and improved functional recovery as assessed by the distance covered in the 6 MWT (mean difference 29.06 meters, 95% CI 26.55 to 31.57, I2 = 42%, p < 0.001). No differences were observed for the rate of overall complications, medical complications 30-day postoperative mortality or hospital readmission.
Conclusion: Our work suggests that prehabilitation is effective in reducing postoperative burden in high-risk cancer patients. Future randomized controlled trials for the high-risk surgical patients, using well-established and clinically relevant outcome measures, and with appropriate sample size calculation are needed.
2. Sullivan R, Alatise OI, Anderson BO, Audisio R, Autier P, Aggarwal A, et al. Global cancer surgery: delivering safe, affordable, and timely cancer surgery. Lancet Oncol. 2015;16(11):1193-224.
3. Handforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, et al. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol. 2015;26(6):1091-101.
4. Fagard K, Leonard S, Deschodt M, Devriendt E, Wolthuis A, Prenen H, et al. The impact of frailty on postoperative outcomes in individuals aged 65 and over undergoing elective surgery for colorectal cancer: A systematic review. J Geriatr Oncol. 2016;7(6):479-91.
5. Oakland K, Nadler R, Cresswell L, Jackson D, Coughlin PA. Systematic review and meta-analysis of the association between frailty and outcome in surgical patients. Annals of the Royal College of Surgeons of England. 2016;98(2):80-5.
6. Merkow RP, Bentrem DJ, Mulcahy MF, Chung JW, Abbott DE, Kmiecik TE, et al. Effect of Postoperative Complications on Adjuvant Chemotherapy Use for Stage III Colon Cancer. Annals of Surgery. 2013;258(6):847-53.
7. Scheede-Bergdahl C, Minnella EM, Carli F. Multi-modal prehabilitation: addressing the why, when, what, how, who and where next? 2019;74(S1):20-6.
8. Carli F, Scheede-Bergdahl C. Prehabilitation to enhance perioperative care. Anesthesiol Clin. 2015;33(1):17-33.
9. Marmelo F, Rocha V, Moreira-Gonçalves D. The impact of prehabilitation on post-surgical complications in patients undergoing non-urgent cardiovascular surgical intervention: Systematic review and meta-analysis. European journal of preventive cardiology. 2018;25(4):404-17.
10. Moran J, Guinan E, McCormick P, Larkin J, Mockler D, Hussey J, et al. The ability of prehabilitation to influence postoperative outcome after intra-abdominal operation: A systematic review and meta-analysis. Surgery. 2016;160(5):1189-201.
11. Kamarajah SK, Bundred J, Weblin J, Tan BHL. Critical appraisal on the impact of preoperative rehabilitation and outcomes after major abdominal and cardiothoracic surgery: A systematic review and meta-analysis. Surgery. 2020;167(3):540-9.
12. Santa Mina D, Clarke H, Ritvo P, Leung YW, Matthew AG, Katz J, et al. Effect of total-body prehabilitation on postoperative outcomes: a systematic review and meta-analysis. Physiotherapy. 2014;100(3):196-207.
13. Gillis C, Buhler K, Bresee L, Carli F, Gramlich L, Culos-Reed N, et al. Effects of Nutritional Prehabilitation, With and Without Exercise, on Outcomes of Patients Who Undergo Colorectal Surgery: A Systematic Review and Meta-analysis. Gastroenterology. 2018;155(2):391-410.e4.
14. Lau CSM, Chamberlain RS. Prehabilitation Programs Improve Exercise Capacity Before and After Surgery in Gastrointestinal Cancer Surgery Patients: A Meta-Analysis. Journal of Gastrointestinal Surgery. 2020;24(12):2829-37.
15. Palma S, Hasenoehrl T, Jordakieva G, Ramazanova D, Crevenna R. High-intensity interval training in the prehabilitation of cancer patients—a systematic review and meta-analysis. Supportive Care in Cancer. 2020.
16. Daniels SL, Lee MJ, George J, Kerr K, Moug S, Wilson TR, et al. Prehabilitation in elective abdominal cancer surgery in older patients: systematic review and meta-analysis. BJS Open. 2020;4(6):1022-41.
17. Milder DA, Pillinger NL, Kam PCA. The role of prehabilitation in frail surgical patients: A systematic review. Acta anaesthesiologica Scandinavica. 2018;62(10):1356-66.
18. Karlsson E, Farahnak P, Franzén E, Nygren-Bonnier M, Dronkers J, van Meeteren N, et al. Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery – A randomized controlled design. PLoS ONE. 2019;14(7):1-21.
19. Barberan-Garcia A, Ubre M, Roca J, Lacy AM, Burgos F, Risco R, et al. Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial. Ann Surg. 2018;267(1):50-6.
20. Carli F, Bousquet-Dion G, Awasthi R, Elsherbini N, Liberman S, Boutros M, et al. Effect of Multimodal Prehabilitation vs Postoperative Rehabilitation on 30-Day Postoperative Complications for Frail Patients Undergoing Resection of Colorectal Cancer A Randomized Clinical Trial. JAMA surgery. 2020;155(3):233-42.
21. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
22. Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions versão 6.0Cochrane, 2019.
23. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557-60.
24. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6):377-84.
25. Chia CL, Mantoo SK, Tan KY. ‘Start to finish trans-institutional transdisciplinary care’: a novel approach improves colorectal surgical results in frail elderly patients. Colorectal Dis. 2016;18(1):O43-50.
26. Mazzola M, Bertoglio C, Boniardi M, Magistro C, De Martini P, Carnevali P, et al. Frailty in major oncologic surgery of upper gastrointestinal tract: How to improve postoperative outcomes. Eur J Surg Oncol. 2017;43(8):1566-71.
27. Souwer ETD, Bastiaannet E, de Bruijn S, Breugom AJ, van den Bos F, Portielje JEA, et al. Comprehensive multidisciplinary care program for elderly colorectal cancer patients: “From prehabilitation to independence”. Eur J Surg Oncol. 2018;44(12):1894-900.
28. Baimas-George M, Watson M, Elhage S, Parala-Metz A, Vrochides D, Davis BR. Prehabilitation in Frail Surgical Patients: A Systematic Review. World Journal of Surgery. 2020;44(11):3668-78.
29. Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005;242(3):326-41; discussion 41-3.
30. Tevis SE, Kohlnhofer BM, Stringfield S, Foley EF, Harms BA, Heise CP, et al. Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival. Dis Colon Rectum. 2013;56(12):1339-48.
31. Vasavada B, patel H. Non surgical procedure related postoperative Complications independently predicts perioperative mortality, in gastrointestinal and Hpb surgeries.- A retrospective Analysis of prospectively maintained data. medRxiv. 2020:2020.04.17.20068940.
32. Yabroff KR, Guy GP, Jr., Ekwueme DU, McNeel T, Rozjabek HM, Dowling E, et al. Annual patient time costs associated with medical care among cancer survivors in the United States. Med Care. 2014;52(7):594-601.
33. Couwenberg AM, de Beer FSA, Intven MPW, Burbach JPM, Smits AB, Consten ECJ, et al. The impact of postoperative complications on health-related quality of life in older patients with rectal cancer; a prospective cohort study. Journal of Geriatric Oncology. 2018;9(2):102-9.
34. Safieddine N, Xu W, Quadri SM, Knox JJ, Hornby J, Sulman J, et al. Health-related quality of life in esophageal cancer: effect of neoadjuvant chemoradiotherapy followed by surgical intervention. J Thorac Cardiovasc Surg. 2009;137(1):36-42.
35. Minnella EM, Awasthi R, Loiselle SE, Agnihotram RV, Ferri LE, Carli F. Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial. JAMA surgery. 2018;153(12):1081-9.
36. Aguayo GA, Donneau A-F, Vaillant MT, Schritz A, Franco OH, Stranges S, et al. Agreement Between 35 Published Frailty Scores in the General Population. American Journal of Epidemiology. 2017;186(4):420-34.