Impact of Obesity on Cancer-Specific Survival and Overall Survival in Colorectal Cancer

Obesity is a well-established risk factor for colorectal cancer (CRC) development, yet its influence on cancer-specific survival (CSS) and overall survival (OS) remains paradoxical. While obesity correlates with adverse outcomes such as increased recurrence, metastasis, and treatment-related complications, emerging evidence highlights a counterintuitive “obesity paradox,” where overweight and moderately obese patients with Body Mass Index(BMI 25–30) exhibit improved CSS and OS compared to underweight (BMI <18.5) or morbidly obese (BMI >35) individuals. Proposed mechanisms for this paradox include altered molecular signaling (adipokine imbalances), enhanced energy metabolism, and greater treatment tolerance due to metabolic reserves. However, these findings are contentious, as BMI, a crude measure, fails to distinguish lean mass from visceral adiposity, key determinants of prognosis. Studies suggest that moderate obesity may buffer treatment toxicity, while extremes of BMI reflect frailty or metabolic dysfunction, worsening survival. This review critically examines the biological underpinnings of the obesity paradox and challenges BMI’s reliability as a prognostic tool. Research must prioritize advanced body composition metrics (visceral fat quantification via imaging) to disentangle obesity’s dual role in CRC outcomes. Such precision could guide tailored interventions, transforming the paradox from a scientific curiosity into a therapeutic strategy, optimizing survival for CRC patients across the weight spectrum. © 2025 Taylor & Francis Group, LLC.