Introduction and Core Highlights
The management of patients with excess weight undergoing colorectal cancer (CRC) resection presents a unique set of clinical challenges, ranging from technical surgical difficulties to an increased risk of postoperative complications. The CARE feasibility randomized clinical trial, recently published in JAMA Network Open, investigated whether a rapid, preoperative weight loss intervention using a total diet replacement (TDR) program is feasible and safe in this population. The findings suggest a paradigm shift in preoperative optimization, challenging the traditional hesitation to recommend weight loss before major oncological surgery.
Key Highlights:
1. Feasibility and Adherence: The intervention was well-tolerated, with 85% attendance at dietetic sessions and 100% patient retention.
2. Significant Weight Loss: 61% of participants in the intervention group achieved a weight loss of 5% or more within a median of 33 days, compared to only 9% in the usual care group.
3. Preservation of Lean Mass: Despite rapid weight loss, there was no evidence of significant fat-free mass (FFM) depletion, a critical finding for maintaining postoperative functional capacity.
4. Clinical Benefits: Exploratory analysis revealed that patients who lost more than 3.2% of their body weight experienced a 50% relative reduction in postoperative complications.
Background: The Burden of Excess Weight in Colorectal Surgery
Obesity is a well-established risk factor for the development of colorectal cancer, but its impact extends far into the perioperative period. For surgeons, excess visceral adiposity complicates laparoscopic and robotic access, obscures anatomical planes, and increases the difficulty of lymphadenectomy. For the patient, excess weight is associated with higher rates of surgical site infections (SSI), prolonged operative times, increased risk of anastomotic leaks, and delayed return of bowel function.
Historically, preoperative weight loss has been viewed with caution in oncology. Concerns regarding the induction of a catabolic state, the potential for sarcopenia (loss of muscle mass), and the delay of definitive cancer treatment have often led clinicians to prioritize immediate surgery over weight optimization. However, the rise of Enhanced Recovery After Surgery (ERAS) protocols has renewed interest in ‘prehabilitation,’ focusing on optimizing a patient’s physiological reserves before the stress of surgery.
Study Design: The CARE Feasibility Trial
The CARE trial was an assessor-blinded, multicenter randomized clinical trial conducted across eight hospitals in England. The study enrolled 71 adults (mean age 64 years) with a BMI of 28 or greater who were scheduled for curative elective CRC resection.
The Intervention
Participants were randomized to either a total diet replacement (TDR) program or usual care. The TDR group received a low-energy diet consisting of approximately 800 kcal/day with a high protein content (76 g/day) provided through nutritionally complete soups, shakes, and bars. This intervention began as soon as the decision to treat was made and continued until the day of surgery. This was supported by regular telephone calls from dietitians to ensure adherence and manage symptoms.
Primary and Secondary Endpoints
The primary focus was feasibility, defined by recruitment rates, engagement, adherence (achieving ≥5% weight loss), and retention. Secondary outcomes included changes in body composition (fat-free mass), postoperative morbidity (using the Clavien-Dindo scale), and patient-reported symptoms such as fecal incontinence and skin integrity.
Key Findings: Feasibility, Safety, and Clinical Outcomes
The CARE trial successfully met its progression criteria for a definitive trial. While recruitment was slightly slower than anticipated (0.57 vs. 0.75 participants per site per month), the engagement and retention were exemplary.
Body Composition and Weight Dynamics
The intervention group lost a mean of 6.1 kg before surgery, which was 4.3 kg more than the control group. Remarkably, the adjusted change in fat-free mass between groups was negligible (0.1 kg), suggesting that the high protein content of the TDR program successfully protected muscle tissue during rapid weight loss. This is a vital clinical distinction, as the loss of lean mass is typically associated with poorer surgical outcomes and delayed recovery.
Surgical Morbidity and Recovery
While the study was not powered to detect definitive differences in complication rates, the data showed no increase in complications in the weight loss group. In fact, an exploratory observational analysis indicated a dose-response relationship: patients who lost more than the median weight (3.2%) had a 50% relative reduction in overall complications (95% CI, 1%-78%). Furthermore, postoperative improvements were noted in specific symptoms; for instance, fecal incontinence and sore skin scores were significantly better in the intervention group compared to usual care.
Economic Viability
Cohort simulation modeling over a 30-year horizon indicated that the preoperative TDR intervention is likely to be cost-effective. By reducing the complexity of surgery and potentially shortening hospital stays through fewer complications, the initial cost of the diet replacement and dietetic support is offset by systemic savings.
Expert Commentary: Challenging the Malnutrition Dogma
The results of the CARE trial provide a compelling argument for reconsidering the ‘obesity paradox’ in surgical oncology. In many clinical settings, any weight loss prior to cancer surgery is flagged as a sign of malnutrition or cachexia. However, this study demonstrates that intentional, nutritionally supported weight loss is physiologically distinct from disease-related wasting.
By providing 76g of protein daily within an 800 kcal limit, the CARE protocol ensures that the body has sufficient amino acids to maintain nitrogen balance, even while in a significant caloric deficit. This allows for the reduction of visceral fat—which improves the surgical field and reduces inflammatory cytokines—without the detrimental loss of skeletal muscle. For health policy experts and clinicians, this suggests that the ‘waiting time’ for surgery can be transformed into an ‘active preparation’ phase, potentially improving the safety profile of CRC resections in patients with high BMI.
Conclusion and Future Directions
The CARE feasibility trial confirms that a short-term, low-energy total diet replacement program is a viable and safe strategy for preoperative optimization in patients with excess weight and colorectal cancer. The high levels of adherence and the lack of adverse effects on muscle mass provide a strong foundation for a larger, definitive Phase III trial aimed at confirming the reduction in postoperative morbidity.
Clinicians should view these findings as an encouragement to integrate nutritional optimization more aggressively into preoperative care. Rather than viewing a BMI ≥ 28 as a fixed risk factor, it should be viewed as a modifiable one that can be addressed within the standard window between diagnosis and surgery.
Funding and Clinical Trial Information
This study was funded by the National Institute for Health and Care Research (NIHR). The trial is registered at ISRCTN.org with the identifier ISRCTN39207707.
References
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.