Urine Glycosaminoglycan Scores for Surveillance of Recurrence in Intermediate and High-risk Non-metastatic Clear Cell Renal Cell Carcinoma – An Observational Prospective Multicenter Diagnostic Test Cohort Study

Abstract

Background and Objective: Non-metastatic clear cell renal cell carcinoma (M0ccRCC) recurs 92 in ~20% of patients within 5 years post-surgery. With no biomarkers available, recurrence 93 detection relies on radiological imaging. Urine glycosaminoglycan profiles (GAGomes) were 94 previously associated with M0ccRCC recurrence. We conducted an observational prospective 95 multicenter diagnostic test cohort study to evaluate GAGomes for post-surgery recurrence 96 detection in M0ccRCC. 97 Methods: Postsurgical M0ccRCC patients with Leibovich score (LS) ≥5 points were included. 98 Follow-up imaging up to 18 months assessed radiological recurrence (reference standard). 99 Urine GAGomes were measured every 3 months to compute a GAGome score (index test). 100 Sensitivity and specificity to radiological recurrence were calculated. Lead time between first 101 positive GAGome score and radiological recurrence was estimated. Bayesian joint modeling 102 estimated recurrence-free survival hazard ratio (HR). 103 Key Findings and Limitations: Of 393 patients screened (Jan 2020–Nov 2021), 134 met 104 inclusion criteria. Median follow-up was 16 months (IQR:12-18) for those without a recurrence. 105 Sixteen percent had a recurrence. The GAGome score had 90% sensitivity (95% CI:62-100%) 106 and 51% specificity (95%CI:30-71%) to radiological recurrence. The positive and negative 107 predictive values were 26%(95%CI:4-46%) and 97% (95%CI:87-100%), respectively. Median 108 lead time was 4.2 months (IQR:1.6–6.4). A 10-point GAGome score increase was associated 109 with a HR=1.62 (95% high density interval:1.11-2.30) for recurrence. Main limitation was short 110 follow-up time. 111 Conclusions and Clinical Implications: GAGome score had very high sensitivity to ccRCC 112 recurrence, resulting in 97% negative predictive value. External validation foreseen in the study 113 design aims to confirm its utility to personalize M0ccRCC follow-up. 114