Plasma and Urine Free Glycosaminoglycans as Monitoring Biomarkers in Nonmetastatic Renal Cell Carcinoma—A Prospective Cohort Study
Journal article, 2022
Objective: To explore whether free GAGomes could detect M0 RCC recurrence noninvasively.
Design, setting, and participants: Between June 2016 and February 2021, we enrolled a prospective consecutive series of patients elected for (1) partial or radical nephrectomy for clinical M0 RCC (cohort 1) or (2) first-line therapy following RCC metachronous metastatic recurrence (cohort 2) at Sahlgrenska University Hospital, Gothenburg, Sweden. The study population included M0 RCC patients with recurrent disease (RD) versus no evidence of disease (NED) in at least one follow-up visit. Plasma and urine free GAGomes—consisting of 40 chondroitin sulfate (CS), heparan sulfate, and hyaluronic acid (HA) features—were measured in a blinded central laboratory preoperatively and at each postoperative follow-up visit until recurrence or end of follow-up in cohort 1, or before treatment start in cohort 2.
Outcome measurements and statistical analysis: We used Bayesian logistic regression to correlate GAGome features with RD versus NED and with various histopathological variables. We developed three recurrence scores (plasma, urine, and combined) proportional to the predicted probability of RD. We internally validated the area under the curve (AUC) using bootstrap resampling. We performed a decision curve analysis to select a cutoff and report the corresponding net benefit, sensitivity, and specificity of each score. We used univariable analyses to correlate each preoperative score with recurrence-free survival (RFS).
Results and limitations: Of 127 enrolled patients in total, 62 M0 RCC patients were in the study population (median age: 63 year, 35% female, and 82% clear cell). The median follow-up time was 3 months, totaling 72 postoperative visits —17 RD and 55 NED cases. RD was compatible with alterations in 14 (52%) of the detectable GAGome features, mostly free CS. Eleven (79%) of these correlated with at least one histopathological variable. We developed a plasma, a urine, and a combined free CS RCC recurrence score to diagnose RD versus NED with AUCs 0.91, 0.93, and 0.94, respectively. At a cutoff equivalent to ≥30% predicted probability of RD, the sensitivity and specificity were, respectively, 69% and 84% in plasma, 81% and 80% in urine, and 80% and 82% when combined, and the net benefit was equivalent to finding an extra ten, 13, and 12 cases of RD per hundred patients without any unnecessary imaging for plasma, urine, and combined, respectively. The combined score was prognostic of RFS in univariable analysis (hazard ratio = 1.90, p = 0.02). Limitations include a lack of external validation.
Conclusions: Free CS scores detected postsurgical recurrence noninvasively in M0 RCC with substantial net benefit. External validity is required before wider clinical implementation.
Patient summary: In this study, we examined a new noninvasive blood and urine test to detect whether renal cell carcinoma recurred after surgery.
Liquid biopsy
Glycosaminoglycans
Renal cell carcinoma
Tumor biomarkers
Author
Francesco Gatto
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Saeed Dabestani
Lund University
Kristianstad Central Hospital
Sinisa Bratulic
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Angelo Limeta
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
F. Maccari
University of Modena and Reggio Emilia
F. Galeotti
University of Modena and Reggio Emilia
N. Volpi
University of Modena and Reggio Emilia
Ulrika Stierner
Sahlgrenska University Hospital
Jens B Nielsen
BioInnovation Institute
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Sven Lundstam
Sahlgrenska University Hospital
European Urology Open Science
26661691 (ISSN) 26661683 (eISSN)
Vol. 42 30-39Subject Categories
Surgery
Urology and Nephrology
DOI
10.1016/j.euros.2022.06.003
PubMed
35911082