Exploration of Predictive Factors for Acute Radiotherapy-Induced Gastro-Intestinal Symptoms in Prostate Cancer Patients

<b>Background</b>: Acute gastrointestinal (GI) toxicity is a frequent adverse effect of pelvic radiotherapy (RT) in prostate cancer and predicts chronic complications. Identifying predictive factors, especially modifiable ones, is essential to guide supportive interventions. <b>Methods</b>: This prospective observational non-randomized cohort included 32 patients with prostate cancer treated with pelvic RT. Patient-reported GI symptoms were measured using the EORTC QLQ-PRT20 module, and clinician-reported toxicity was graded with CTCAE v5.0. Associations between GI outcomes and clinical, demographic, and lifestyle variables-including the systemic immune-inflammation index (SII) and the Diet Quality Index (DQI)-were examined using uni- and multivariable models. <b>Results</b>: Ninety-one percent of patients reported worsening GI symptoms during RT (median QLQ-PRT20 score increased from 4.2 to 26.8, <i>p</i> < 0.0001). In our final model, higher SII values were independently associated with greater symptom worsening (<i>p</i> = 0.001), whereas obesity (<i>p</i> = 0.03) and higher diet quality (<i>p</i> = 0.015) were protective. No significant interactions were found between SII and BMI or DQI, although diet quality partially attenuated the association between SII and symptom progression. Clinician-reported grade ≥ 2 GI toxicity occurred in 41% of patients and was significantly less frequent in obese individuals (adjusted OR = 0.04, 95% CI 0.0009-0.57, <i>p</i> = 0.02), with higher SII tending to increase risk and higher DQI showing a protective trend. <b>Conclusions</b>: In this exploratory analysis, systemic inflammation was associated with increased GI symptom burden, whereas obesity appeared to mitigate both patient- and clinician-reported outcomes. Higher dietary quality was similarly protective for patient-reported symptoms and showed a non-significant protective trend for clinician-reported toxicity. These findings highlight the interplay between metabolic and inflammatory status in shaping RT-related GI outcomes and support integrating nutritional and inflammatory profiling to guide personalized preventive strategies.