Does Prehabilitation in Colorectal Cancer Surgery Improve Functional Capacity, Quality of Life, and Reduce Postoperative Complications?

A Cochrane Review Summary With Commentary

The aim of this commentary is to discuss from a rehabilitation perspective the Cochrane Review “Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery” by Molenaar et al.¹ (https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013259.pub2/full), published by Cochrane Colorectal Group. This Cochrane Corner is produced in agreement with the American Journal of Physical Medicine and Rehabilitation by Cochrane Rehabilitation with views of the review summary authors in the “implications for practice” section.

Background: Colorectal cancer is more common in the older people and is considered the fourth most deadly cancer. However, over the past few decades, its incidence in people younger than 50 yrs is increasing.² Colorectal cancers are associated with poor health-related quality of life (HRQoL) due to direct consequences of disease (anemia, fatigue, abdominal pain, change in bowel habits) and adverse effects of treatment.³ Prognosis of colorectal cancer is guarded except for patients with nonmetastatic disease.³ Surgical resection of tumor is the cornerstone for treatment.³ There is evidence that postoperative rehabilitation substantially improves functional outcomes and enhance recovery in these patients.⁴ However, data regarding the efficacy of multimodal prehabilitation in improving functional status and HRQoL in patients with nonmetastatic colorectal cancer are limited.

Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery (Molenaar CJL, van Rooijen SJ, Fokkenrood HJP, Roumen RMH, Janssen L, Slooter GD, 2022).

WHAT IS THE AIM OF THIS COCHRANE REVIEW?

The aim of this Cochrane Review was to determine the effects of multimodal prehabilitation programs on functional capacity, postoperative outcomes, and HRQoL in patients with colorectal cancer undergoing surgery.

WHAT WAS STUDIED IN THE COCHRANE REVIEW?

The review included adult patients (>18 yrs) with nonmetastatic colorectal cancer, scheduled for elective surgery for tumor resection. Randomized controlled trials (RCTs) including pilot RCTs, multiarm RCTs, and cluster RCTs were included in this review. Multiple interventions were studied with a duration of intervention greater than 7 days and more than 4 wks of postoperative follow-up. These included physical exercise programs, nutritional support, mental support, or intervention to reduce substance abuse. The intervention was compared with the control group, which did not receive any prehabilitation. The primary outcomes studied were postoperative functional capacity assessed by 6-min walking test (6MWT), postoperative complication rate, and patient-reported HRQoL (assessed by the 36-Item Short Form Survey, Hospital Anxiety and Depression Scale, EuroQol-5D, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core module and ColoRectal cancer module). The secondary outcomes included 6MWT presurgery after completion of the prehabilitation program, handgrip strength (in kilograms), length of hospital stay (in days), overall mortality at maximal follow-up period, compliance rate to the program, safety of prehabilitation interventions, return to normal activities, and readmission rates. Outcomes were measured at baseline, presurgery (after the prehabilitation program), and 4/8 wks after surgery.

SEARCH METHODOLOGY AND UP-TO-DATENESS OF THE COCHRANE REVIEW?

The review authors searched for studies that had been published up to 2021 from Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1950–2021), Embase (Ovid, 1974–2021), and PsycINFO (EBSCOhost, 1967–2021). They also searched the following registries: US National Library of Medicine clinical trials register, Google Scholar, Netherlands Trial Register, and World Health Organization International Clinical Trials Registry Platform. References of included studies were also searched for eligible studies. There was no language restriction.

WHAT ARE THE MAIN RESULTS OF THE COCHRANE REVIEW?

The review included three RCTs with 250 participants (130 in prehabilitation group and 120 in control group). All studies were conducted in Canada, surgery was mainly performed laparoscopically, and most patients were older than 75 yrs. The main results were as follows:

• 1) The 6MWT score measured was better in prehabilitation group, after 4-wk postsurgery; however, it was not statistically significant (n = 131, 95% confidence interval [CI] = −13.81 to 65.85; P = 0.20; I² = 41%; low-certainty evidence). The 6MWT score also favored prehabilitation group after 8-wk postsurgery; however, it was not statistically significant (n = 140; confidence interval = −8.88 to 62.04; P = 0.14; I² = 65%; very low-certainty evidence).
• 2) The information provided was inadequate to calculate postoperative complication rate by Clavien-Dindo scale or Comprehensive Complication Index. Therefore, percentage of participants having at least one postoperative complication within 30 days of surgery was analyzed, which favored prehabilitation group, but it may not be clinically and statistically significant because of small effect size of risk ratio (RR) and P value of 0.75 (n = 250; RR = 0.95, 95% CI = 0.70 to 1.29; P = 0.75; I² = 0%; low-certainty evidence).
• 3) The composite score of only physical and mental subscales of the 36-Item Short Form Survey were reported by Carli et al.⁵ However, Gillis et al.⁶ reported scores for all the subscales of the 36-Item Short Form Survey. Because of this discrepancy of the reported results, pooled analysis of 36-Item Short Form Survey could not be done.
• 4) The mean difference of 6MWT presurgery was 24.91 meters in favor of prehabilitation (n = 225, 95% CI = 11.24 to 38.57; P = 0.0004; I² = 55%; moderate certainty of evidence).
• 5) No quantitative analysis was done for compliance as well as for effect on VO₂peak, handgrip strength, length of hospital stay, mortality rate, return to normal activities, and safety of the program, because of missing or insufficient data.^5–7
• 6) No serious adverse effects were reported by Carli et al.⁵ Other trials did not mention adverse events.
• 7) The relative risk for admission to emergency department within 30 days after surgery was in favor of prehabilitation group with RR of 0.72; however, it was not statistically significant (n = 250; RR = 0.72; CI = 0.39 to 1.32; P = 0.28; I² = 0%; low-certainty evidence).
• 8) Readmission rate within 30 days after surgery was higher in the prehabilitation group, which was statistically insignificant (RR = 1.20, 95% CI = 0.54 to 2.65; P = 0.65; I² = 43%; low-certainty evidence).

WHAT DID THE AUTHORS CONCLUDE?

The authors concluded that in patients with colorectal cancer undergoing surgery, who practiced multimodal prehabilitation, there was an improvement in functional capacity measured by 6MWT before and after surgery, reduced postoperative complications, and reduced number of emergency department visits within 30 days of surgery, which was statistically not significant with low certainty of evidence. However, the number of readmissions was higher in the prehabilitation group. Because of the high risk of bias, imprecision, and inconsistency, the certainty of evidence ranged from moderate to very low.

WHAT ARE THE IMPLICATIONS OF THE COCHRANE EVIDENCE FOR PRACTICE IN REHABILITATION?

Rehabilitation for patients with cancer is finding growing interest in recent times. There is evidence that multidisciplinary cancer rehabilitation can improve functional outcomes, reduce disability, and enhance HRQoL.⁸ Many rehabilitation professionals and stakeholders are actively involved worldwide in providing cancer-related rehabilitation services. However, most of these services are provided after surgery and other cancer-related treatments. In this scenario, prehabilitation seems helpful in improving functional outcomes in patients who undergo abdominal aortic aneurysm repair, coronary artery bypass grafting, and bariatric surgery.⁹ Therefore, rehabilitation professionals should consider prehabilitation also for patients undergoing surgery for tumor resection. As reported by this Cochrane Systematic Review, it has the potential to improve some outcomes such as functional capacity addressed with 6MWT in patients undergoing colorectal cancer surgery. However, considering the overall moderate to very low quality of evidence for prehabilitation in this population, larger trials in various settings are needed using multiple combinations of prehabilitation to demonstrate the effect of prehabilitation in these patients.