A Pragmatic Non-Randomized Trial of Prehabilitation Prior to Cancer Surgery: Study Protocol and COVID-19-Related Adaptations

Daniel Santa Mina; Daniel Sellers; Darren Au; Shabbir M H Alibhai; Hance Clarke; Brian H Cuthbertson; Gail Darling; Alaa El Danab; Anand Govindarajan; Karim Ladha; Andrew G Matthew; Stuart McCluskey; Karen A Ng; Fayez Quereshy; Keyvan Karkouti; Ian M Randall

doi:10.3389/fonc.2021.629207

A Pragmatic Non-Randomized Trial of Prehabilitation Prior to Cancer Surgery: Study Protocol and COVID-19-Related Adaptations

Front Oncol. 2021 Mar 10:11:629207. doi: 10.3389/fonc.2021.629207. eCollection 2021.

Authors

Daniel Santa Mina^{1

2

3}, Daniel Sellers^{2

3}, Darren Au³, Shabbir M H Alibhai^{2

4}, Hance Clarke^{2

3}, Brian H Cuthbertson^{2

5}, Gail Darling^{2

6}, Alaa El Danab⁷, Anand Govindarajan^{2

8}, Karim Ladha^{2

9}, Andrew G Matthew^{2

6}, Stuart McCluskey^{2

3}, Karen A Ng^{2

10}, Fayez Quereshy^{2

6}, Keyvan Karkouti^{2

3}, Ian M Randall^{2

3}

Affiliations

¹ Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.
² Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³ Department of Anesthesia and Pain Management, University Health Network, Toronto, ON, Canada.
⁴ Division of General Internal Medicine and Geriatrics, University Health Network, Toronto, ON, Canada.
⁵ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁶ Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁷ Clinical Nutrition, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
⁸ Department of Surgery, Sinai Health System, Toronto, ON, Canada.
⁹ Department of Anesthesia, St. Michael's Hospital, Toronto, ON, Canada.
¹⁰ Department of Geriatrics, Sinai Health System, Toronto, ON, Canada.

Abstract

Background: Experimental data highlight the potential benefits and health system cost savings related to surgical prehabilitation; however, adequately powered randomized controlled trial (RCT) data remain nascent. Emerging prehabilitation services may be informed by early RCT data but can be limited in informing real-world program development. Pragmatic trials emphasize external validity and generalizability to understand and advise intervention development and implementation in clinical settings. This paper presents the methodology of a pragmatic prehabilitation trial to complement emerging phase III clinical trials and inform implementation strategies.

Methods: This is a pilot pragmatic clinical trial conducted in a large academic hospital in Toronto, Ontario, Canada to assess feasibility of clinical implementation and derive estimates of effectiveness. Feasibility data include program referral rates, enrolment and attrition, intervention adherence and safety, participant satisfaction, and barriers and facilitators to programming. The study aims to receive 150 eligible referrals for adult, English-speaking, preoperative oncology patients with an identified indication for prehabilitation (e.g., frailty, deconditioning, malnutrition, psychological distress). Study participants undergo a baseline assessment and shared-decision making regarding the intervention setting: either facility-based prehabilitation or home-based prehabilitation. In both scenarios, participants receive an individualized exercise prescription, stress-reduction psychological support, nutrition counseling, and protein supplementation, and if appropriate, smoking cessation program referrals. Secondary objectives include estimating intervention effects at the week prior to surgery and 30 and 90 days postoperatively. Outcomes include surgical complications, postoperative length of stay, mortality, hospital readmissions, physical fitness, psychological well-being, and quality of life. Data from participants who decline the intervention but consent for research-related access to health records will serve as comparators. The COVID-19 pandemic required the introduction of a 'virtual program' using only telephone or internet-based communication for screening, assessments, or intervention was introduced.

Conclusion: This pragmatic trial will provide evidence on the feasibility and viability of prehabilitation services delivered under usual clinical conditions. Study amendments due to the COVID-19 pandemic are presented as strategies to maintain prehabilitation research and services to potentially mitigate the consequences of extended surgery wait times.

Keywords: cancer; cancer surgery; feasibility; health quality; implementation science; pragmatic trial; prehabilitation.