Preoperative Calorie Restriction and Exercise in Patients With Obesity Undergoing Colorectal Cancer Resection (PRECAREX)

Usual care group will follow the usual institutional preoperative care

Participants allocated to usual care will follow the 2025 standard ERAS-based perioperative pathway, including routine preoperative assessment, perioperative management, and postoperative follow-up. This may include standard nutritional screening and nutritional optimization according to hospital protocols and ERAS recommendations, including oral nutritional supplementation or immunonutrition when clinically indicated as part of routine care and independently of study allocation. No structured weight loss program, supervised exercise, or research-prescribed individualized hypocaloric dietary intervention will be provided. Physical activity and dietary intake will be monitored to account for potential behavioral changes and to document any usual-care nutritional or lifestyle advice received outside the intervention.

Preoperative calorie restriction and supervised exercise

Participants allocated to PRECAREX will complete a structured preoperative weight loss intervention combining individualized controlled caloric restriction and supervised combined exercise training. The intervention will last approximately 4 weeks, depending on the interval between inclusion and surgery. Its objective is to induce a controlled preoperative weight loss of approximately 5%, while preserving skeletal muscle function and improving functional reserve, with the primary clinical aim of reducing postoperative morbidity. The program is conceived as a supervised metabolic intervention targeting the biological profile of patients with obesity, characterized by excess adiposity, metabolic dysfunction, systemic inflammation, and reduced physiological adaptability.

Feasibility will be assessed through recruitment and retention rates, attendance at supervised exercise sessions, and adherence to the prescribed calorie restriction.

Safety will be assessed by recording adverse events occurring during the intervention, including their severity.

Overall postoperative complication burden assessed using the Comprehensive Complication Index, which integrates all postoperative complications into a score ranging from 0 (no complications) to 100 (death).

Proportion of participants experiencing at least one postoperative complication, expressed as a percentage.

Proportion of participants experiencing major postoperative complication (CCI > 20), expressed as a percentage.

Proportion of participants experiencing at least one medical complication, expressed as a percentage.

Proportion of participants experiencing at least one surgical complication, expressed as a percentage.

Number of days from surgery to discharge from the hospital.

Proportion of participants attending emergency department after discharge, expressed as a percentage.

Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the glycemic profile. We will obtain plasma glucose (mg/dL) and insulin (mg/dL) levels.

Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the lipid profile. We will obtain total cholesterol (mg/dL), Light-Density Lipoprotein Cholesterol (mg/dL), High-Density Lipoprotein Cholesterol (mg/dL), and Triglycerides (mg/dL) levels.

Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the hepatic transaminases levels. Serum alanine aminotransferase (ALT), aspartate aminotransferase (GOT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) will be measured and expressed in units per litre (U/L).

Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the immunological blood profiles. The following parameters will be obtained: Leukocytes (10*3 uL), Neutrophils (10*3 uL), Lymphocytes (10*3 uL), Monocytes (10*3 uL), Eosinophils (10*3 uL), Basophils (10*3 uL) and LUC cells (10*3 uL).

Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the red cells levels, including red blood cell count (×10^12/L), haemoglobin (g/dL), haematocrit (%), mean corpuscular volume (fL), mean corpuscular haemoglobin (pg), mean corpuscular haemoglobin concentration (g/dL), and red cell distribution width (%).

Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the tumour markers levels (CA 19-9, CEA, CA 125, TPA and CA 15.3; all will be expressed as pg/mL))

Changes in systolic blood pressure will be assessed by blood pressure monitor.

Changes in diastolic blood pressure will be assessed by blood pressure monitor.

Changes in cardiorespiratory fitness assessed using the six-minute walk test.

Changes in upper body muscular strength assessed through handgrip test.

Changes in lower body muscular strength will be assessed using the 30 seconds sit-to-stand test.

Changes in lower body muscular strength will be assessed using the 5 sit-to-stand test

Body weight (kilograms) will be measured by a digital scale

Body height (meters and centimeters) will be measured by a stadiometer

Fat mass will be assessed by assessed by bioelectrical impedance analysis (BIA).

Fat-free Mass will be assessed by assessed by bioelectrical impedance analysis (BIA).

Neck circumference will be assessed by measuring tape following the procedures outlined by the International Society for the Advancement of Kinanthropometry

Waist circumference will be assessed by measuring tape following the procedures outlined by the International Society for the Advancement of Kinanthropometry

Hip circumference will be assessed by measuring tape following the procedures outlined by the International Society for the Advancement of Kinanthropometry

Changes in health-related quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). This 30-item questionnaire comprises five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single-item measures (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties). All scale and single-item scores are transformed to a range of 0-100. Higher functional and global health status/quality of life scores indicate better functioning and quality of life, whereas higher symptom and financial difficulties scores indicate greater problems.

Changes in fatigue assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cancer Related Fatigue Module (EORT-QLQ-FA12). This is a 12-item validated multi-dimensional questionnaire evaluating physical fatigue (5 items), emotional fatigue (3 items), cognitive fatigue (2 items), and interference/social impact (2 single items) over the past week. Items are scored on a 4-point Likert scale (1 = Not at all, 4 = Very much). Raw scores for each subscale are linearly transformed into a standardized 0 to 100 metric. Higher scores indicate a higher level of fatigue severity and greater functional impairment.

General health will be assessed by the EuroQol 5 dimensions 5 levels (EQ-5D-5L). Values ranged from 0 to 100. Higher values mean better outcome.

Changes in anxiety and depressive symptoms assessed using the Hospital Anxiety and Depression Scale (HADS). Minimum value: 0 // Maximum value: 21. Higher scores mean a better outcome.

Changes in sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI global score ranges from 0 to 21, with a score higher than 5 indicating poor sleep quality

Changes in dietary pattern assessed using the Food Frequency Questionnaire (FFQ).

Colon tumor tissue samples will be collected during surgical resection and analyzed using molecular techniques (e.g., gene expression profiling) to assess markers associated with tumor progression.

Shotgun metagenomic sequencing of DNA extracted from stool samples to determine microbial functional capacity through the analysis of metabolic pathways.