Decision making for anti-VEGF inhibitor continuation: dip stick? or urine protein/creatinine ratio? (VERSiON UP study)

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Monitoring proteinuria is important for the management of patients with cancer treated with anti-vascular endothelial growth factor (VEGF) or anti-VEGF receptor (VEGFR) inhibitors (VEGF/Ri). Here we investigated the difference between the urine protein/creatinine ratio (UPCR) and a qualitative value test (QV) on the decision making of treatment continuation and the usefulness of UPCR testing in patients with gastrointestinal cancer treated with anti-VEGF/Ri.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>From January 2017 to December 2018, a survey was conducted based on the medical records of patients with gastrointestinal cancer with a QV of ≥2+ during the use of anti-VEGF/Ri at seven Japanese institutions participating in the Onco-nephrology Consortium. The primary endpoint was the ratio of the worst UPCR < 2.0 (low UPCR) in cases with a QV2+ at the point of the first proteinuria onset. The secondary endpoints were a comparison of low UPCR and worst UPCR ≥2.0 (high UPCR), the concordance rate between UPCR and QV in the Common Terminology Criteria for Adverse Events (CTCAE) grading, and the differences in the decision making for anti-VEGF/Ri continuation.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Among the 71 patients enrolled, the proportion of low UPCR in onset QV2+ (<jats:italic>n</jats:italic> = 53) was 66% (<jats:italic>n</jats:italic> = 35). In a comparison between low (<jats:italic>n</jats:italic> = 36) and high UPCR cases (<jats:italic>n</jats:italic> = 24), body weight (<jats:italic>P</jats:italic> = 0.036), onset QV status (<jats:italic>P</jats:italic> = 0.0134), and worst QV status (<jats:italic>P</jats:italic> < 0.0001) were significantly associated with UPCR levels. The concordance rate for CTCAE Grade 2 of both the QV and UPCR was 83%. Regarding the judgment of anti-VEGF/Ri continuation, treatment was continued in 42.4% of cases when the QV became 3+, whereas only 25% continued treatment when the UPCR value became high.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Urine dipstick test results may overestimate proteinuria, and the UPCR result tended to be more critical than the QV when deciding the treatment policy.</jats:p> </jats:sec><jats:sec> <jats:title>Trial registration</jats:title> <jats:p>This study is a multiple institutional retrospectively registered observational trial. Clinical Trial number: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (protocol ID <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048563">UMIN000042545</jats:ext-link>).</jats:p> </jats:sec>