Predictive Factors for Gastrointestinal and Hepatic Adverse Events During 5‐Aminolevulinic Acid–Guided Photodynamic Diagnosis in Bladder Cancer: Exploratory Analysis of the Phase III SPP2C102 Trial

ABSTRACT Objective To evaluate the incidence and clinical predictors of gastrointestinal and hepatic adverse events following oral administration of 5‐aminolevulinic acid hydrochloride (5‐ALA) before transurethral resection of bladder tumors (TURBT). Methods Safety data were analyzed from 145 patients enrolled in the prospective, single‐arm, multicenter phase III SPP2C102 trial who received 5‐ALA 4–8 h before TURBT. The incidence and severity of nausea, vomiting, and liver dysfunction, defined by elevations in aspartate aminotransferase, alanine aminotransferase, and/or gamma‐glutamyltransferase, were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Potential risk factors were evaluated using univariable and multivariable logistic regression; results are reported as adjusted odds ratios (aOR) with 95% confidence intervals (CIs). Results Nausea/vomiting occurred in 28/145 patients (19.3%), all CTCAE grade 1–2. Female sex was independently associated (aOR 3.15, 95% CI 1.17–8.47), and diastolic blood pressure ≥ 80 mmHg showed a borderline association (aOR 2.37, 95% CI 0.99–5.78). Prophylactic antiemetics yielded a numerically lower rate (21.1% vs. 9.1%; p = 0.25). Liver‐enzyme elevations similarly occurred in 28/145 patients (19.3%), all CTCAE grade 1–2. Systolic blood pressure ≥ 130 mmHg remained independently associated (aOR 4.73, 95% CI 1.62–13.78), whereas associations for hypertensive comorbidity and BMI ≥ 25 kg/m 2 in univariable analyses did not persist after adjustment. Conclusion 5‐ALA–related nausea, vomiting, and transient liver‐enzyme elevations were common but generally mild. Simple bedside variables—particularly sex and blood pressure—may guide selective antiemetic prophylaxis and closer biochemical monitoring in routine practice.