Quality of Life of Colorectal Cancer Patients Treated with Chemotherapy

<b>Background/Objectives:</b> Colorectal cancer (CRC) is associated with anorexia-cachexia syndrome, which negatively affects health-related quality of life (HRQoL). This study aimed to evaluate HRQoL and functional status in CRC patients undergoing chemotherapy who were eligible for oral nutritional supplementation (ONS). <b>Methods:</b> In this prospective, randomized study, 72 patients with stage II-IV CRC were enrolled (40 intervention group [IG], 32 control group [CG]). IG received ONS (2 × 125 mL/day, 600 kcal, 36 g protein) for 12 weeks, while CG received dietary counseling only. HRQoL was assessed every 4 weeks with the Functional Assessment of Anorexia/Cachexia Therapy (FAACT, version 4.0). Functional status was evaluated with the Karnofsky scale. Nutritional status was assessed using the Subjective Global Assessment (SGA), Nutritional Risk Screening (NRS-2002), and body mass index (BMI), and appetite was assessed on a visual analogue scale (VAS). Clinical Trial Registration: ClinicalTrials.gov, NCT02848807. <b>Results:</b> Mean FAACT score did not differ significantly between groups over 12 weeks (101.0 ± 22.8, 95% CI: 94.6-107.4 vs. 105.1 ± 21.4, 95% CI: 99.1-111.1; <i>p</i> = 0.06). However, the observed difference corresponded to an effect size at the lower bound of the moderate range. However, minimally important difference (MID) analysis demonstrated that clinically meaningful improvement was significantly more frequent in IG than in CG for global FAACT (32% vs. 8%; <i>p</i> = 0.03, OR = 5.50, 95% CI: 1.10-27.62, φ = 0.29), physical well-being (32% vs. 8%; <i>p</i> = 0.03, OR = 5.50, 95% CI: 1.10-27.62, φ = 0.29), and emotional well-being (38% vs. 4%; <i>p</i> = 0.002, OR = 14.86, 95% CI: 1.79-123.36, φ = 0.40). Functional well-being and anorexia/cachexia concerns showed favorable, but nonsignificant, trends (FWB improvement: 29% vs. 8%, <i>p</i> = 0.05, OR = 4.79, 95% CI: 0.95-24.27, φ = 0.26; ACS deterioration: 3% vs. 20%, <i>p</i> = 0.07, OR = 0.12, 95% CI: 0.01-1.11, φ = 0.28). HRQoL correlated positively with nutritional status, appetite, and functional performance, while Karnofsky scores remained stable in both groups. <b>Conclusions:</b> ONS did not significantly change the mean QoL scores at the group level but increased the proportion of patients achieving clinically meaningful improvement, particularly in the physical and emotional domains. These findings suggest that ONS may benefit selected patients who respond to nutritional interventions, underscoring the clinical relevance of individualized nutrition strategies in oncology.