Evaluation of Treatment Continuation and Tolerability Using the Urine Protein-to-Creatinine Ratio (UPC Ratio) as a Criterion for Proteinuria in Patients with Colorectal Cancer Receiving Bevacizumab

Bevacizumab is an antineoplastic anti-angiogenic agent that inhibits vascular endothelial growth factor, and proteinuria is a representative adverse event associated with its use. Proteinuria is evaluated using qualitative urine protein testing, quantitative urine protein measurement based on 24-hour urine collection, or the urine protein-to-creatinine ratio (UPC ratio); however, criteria for treatment decisions differ according to the cancer type. In colorectal cancer, qualitative urine protein testing and 24-hour urine protein measurement are commonly used, whereas standardized UPC ratio-based criteria have not been established. Because bevacizumab enhances the efficacy of chemotherapy in colorectal cancer, inappropriate discontinuation owing to uncertain proteinuria assessment may reduce treatment intensity. We conducted a prospective, single-center, non-randomized interventional study to evaluate whether UPC ratio-based treatment decisions could improve bevacizumab continuation without compromising tolerability. The UPC ratio was prospectively applied to treatment decision-making, and a cutoff 2.0 for continuation was predefined with reference to ramucirumab, an anti-angiogenic agent with a similar mechanism of action. Patients with colorectal cancer who received bevacizumab at Juntendo University Nerima Hospital between September 2020 and March 2021 were enrolled. Proteinuria was assessed using the UPC ratio, and bevacizumab was continued in patients with a UPC ratio < 2.0. Tolerability was evaluated based on the occurrence of nephrotic syndrome and renal dysfunction. Sixteen patients with 84 measurements were analyzed. Among the 20 measurements with qualitative urine protein levels ≥ 2 +, 16 had a UPC ratio < 2.0, and bevacizumab treatment was continued. No nephrotic syndrome or clinically significant renal dysfunction occurred, but generalizability is limited.