Intensive Weight Loss Before Colorectal Cancer Surgery Safe, Feasible

New research is shedding light on the feasibility and safety of intentional weight loss with a low-energy total diet replacement before colorectal cancer surgery in patients with colorectal cancer and excess weight.1

Findings from the multicenter, external, feasibility, parallel, individually randomized CARE trial show a low-energy total diet replacement before colorectal cancer resection is feasible and well tolerated, lacks safety concerns, and is likely cost-effective.1

According to the World Health Organization, colorectal cancer is the third most common cancer worldwide, accounting for approximately 10% of all cancer cases and is the second leading cause of cancer-related deaths worldwide. Surgical resection is part of the standard treatment for most patients but carries a higher risk of postoperative morbidity than many other major abdominal operations. This risk can be further heightened by excess weight.1,2

“In bariatric surgery, preoperative weight loss is associated with better outcomes. However, the short interval between diagnosis and treatment in colorectal cancer necessitates an intensive weight loss intervention,” Dimitrios Koutoukidis, PhD, an associate professor on Diet and Obesity at University of Oxford, and colleagues wrote.1 “It is unclear whether people with cancer will enroll in and adhere to such a program during this unsettling period. There is little evidence from clinical trials on the benefits and risks of substantial intentional weight loss in this setting.”

To address this gap in research, investigators conducted an assessor-blinded randomized clinical trial performed between March 2023 and August 2024 with a 30-day postoperative follow-up in adults with a body mass index ≥ 28 who were awaiting curative elective colorectal cancer resection at 8 hospitals across England. Participants were randomly assigned in a 1:1 ratio to either a low-energy total diet replacement program or standard care.1

In addition to their local standard care pathway, participants in the intervention group were asked to replace all their foods with 4 nutritionally complete meal replacement products per day until their surgery. These meals provided approximately 800 kcal/d, including 76 g/d of protein with the nutritional composition aligned with regulatory requirements. Participants had a 45-minute introductory telephone consultation with a dietitian, weekly 20-minute follow-up calls, and a 10-minute exit call. Participants in the control group followed their local standard care pathway.1

Investigators outlined 5 predefined feasibility aspects to assess progression to a definitive trial: recruitment of ≥ 72 patients, engagement with ≥75% of dietetic telephone calls attended, adherence (≥60% of intervention participants achieving ≥5% weight loss), and ≥ 85% retention. Secondary outcomes included morbidity, symptoms, and changes in weight and fat-free mass. Outcomes were modeled during a 30-year time horizon using cohort simulation.1

Of the 150 potentially eligible participants approached, 71 eligible randomized participants undergoing surgery (n = 36 in the intervention group and n = 35 in the usual care group) were included in the analysis. Among the cohort, the mean age was 64 (standard deviation [SD], 8.7) years, 61% of patients were male, and the mean body mass index was 35.4 (SD, 5.4).1

Investigators noted participants were accrued at a rate of 0.57 participants per site per month compared with the anticipated rate of 0.75. Participants attended 85% of their dietetic calls.1

The median period from randomization to surgery was 33 (interquartile range, 25 to 43) days, during which 22 (61%) of the intervention participants and 3 (9%) of the usual care participants lost ≥ 5% of their weight (odds ratio, 16.8; 95% CI, 4.3 to 65.3). Results showed intervention participants lost a mean of 6.1 (SD, 3.0) kg before surgery, which was 4.3 kg (95% CI, 2.7 to 5.8 kg) more than the usual care participants. Further analysis revealed the between-group adjusted change in fat-free mass was 0.1 kg (95% CI, −3.9 to 4.0 kg).1

Investigators did not observe any difference between the 2 groups regarding the proportion of patients with any complications (39% vs 40%) or with Clavien-Dindo grade I, II, or III complications. Of note, fecal incontinence (−8.6 points; 95% CI, −16.7 to −0.5 points) and sore skin (−15.9 points; 95% CI, −25.3 to −6.6 points) improved postoperatively in the intervention compared with usual care group, and there were no intervention-related serious adverse events.1

Retention was 100%, exceeding the 85% goal. In an exploratory observational analysis, participants who lost ≥ 3.2% of their body weight had a 50% relative reduction in complications (95% CI, 1% to 78%).1

The incremental cost-effectiveness ratio was estimated to be £7623, or $10,193.40 USD, per quality-adjusted life-year, and the probability that the intervention would be cost-effective at the conventional willingness-to-pay threshold of £20,000, or $26,742.08 USD, was 61%.1

“An intensive preoperative weight loss intervention was safe, feasible, and likely cost-effective as part of prehabilitation before colorectal cancer surgery with evidence of improvements in key symptoms,” investigators concluded.1 “Some challenges to recruitment need to be addressed before a definitive trial assesses perioperative and longer-term outcomes.”

References

1. Koutoukidis DA, Jebb SA, Reynolds S, et al. Preoperative Weight Loss in Patients With Excess Weight and Colorectal Cancer: The CARE Feasibility Randomized Clinical Trial. JAMA Netw Open. 2025;8(12):e2547126. doi:10.1001/jamanetworkopen.2025.47126

2. World Health Organization. Colorectal cancer. July 11, 2023. Accessed December 12, 2025. https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer