Nonmetastatic (M0) clear cell renal cell carcinoma (ccRCC) recurs in ∼20% of patients within 5 yr after surgery. With no biomarkers available, recurrence detection relies on radiological imaging.
Urine glycosaminoglycan profiles (GAGomes) were previously associated with M0 ccRCC recurrence. We conducted an observational prospective multicentre diagnostic test cohort study to evaluate GAGomes for postsurgery recurrence detection in M0 ccRCC.
Postsurgical M0 ccRCC patients with a Leibovich score of ≥5 points were included. Follow-up imaging up to 18 mo assessed radiological recurrence (reference standard). Urine GAGomes were measured every 3 mo to compute a GAGome score (index test). Sensitivity and specificity to radiological recurrence were calculated. The lead time between the first positive GAGome score and radiological recurrence was estimated. Bayesian joint modelling estimated recurrence-free survival hazard ratio (HR).
Of the 393 patients screened (January 2020 to November 2021), 134 met the inclusion criteria. The median follow-up was 16 mo (interquartile range [IQR]: 12-18) for those without recurrence. At the last follow-up visit, 16% had recurred. The GAGome score had 90% sensitivity (95% confidence interval [CI]: 62-100%) and 51% specificity (95% CI: 30-71%) to radiological recurrence. The positive and negative predictive values were 26% (95%CI: 4-46%) and 97% (95% CI: 87-100%), respectively. The median lead time was 4.2 mo (IQR: 1.6-6.4). A 10-point GAGome score increase was associated with an HR of 1.62 (95% high density interval: 1.11-2.30) for recurrence. The main limitation was short follow-up time.
GAGome score had very high sensitivity to ccRCC recurrence, resulting in a negative predictive value of 97%. External validation foreseen in the study design aims to confirm its utility to personalise follow-up for M0 ccRCC patients.
European urology oncology. 2025 Aug 20 [Epub ahead of print]
Saeed Dabestani, Nessn H Azawi, Riccardo Campi, Petrus Järvinen, Harry Nisen, Umberto Capitanio, Tommy Kjærgaard Nielsen, Giuseppe Simone, Mark Rochester, Euan Green, Sergio Fernandez-Pello, Christopher Blick, Francesco Porpiglia, Alexandre Ingels, Sinisa Bratulic, Alessandro Antonelli, A Ari Hakimi, Michael A S Jewett, Börje Ljungberg, Bimal Bhindi, Lorenzo Marconi, Alexander Laird, Grant D Stewart, Rajesh Nair, Lars Lund, Neil Barber, Viraj A Master, Andrea Minervini, Jose A Karam, Francesco Gatto, Axel Bex
Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden; Department of Urology, Kristianstad Central Hospital, Region Skane, Kristianstad, Sweden. Electronic address: ., Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, Florence, Italy., Department of Urology, Helsinki University Hospital, Helsinki, Finland., IRCCS San Raffaele Scientific Institute, Urological Research Institute (URI), Milan, Italy., Department of Urology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark., Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy., Department of Urology, Norfolk & Norwich University Hospital, Norwich, UK; Norwich Medical School, UEA, Norwich, UK., Department of Urology, Salford Royal Hospital, Northern Care Alliance, Salford, UK., Department of Urology, Cabueñes University Hospital, Gijón, Spain., Harold Hopkins Department of Urology, Royal Berkshire Hospital, Reading, UK., Department of Oncology, Division of Urology, University of Turin, San Luigi Gonzaga Hospital, Turin, Italy., Department of Urology, Henri Mondor Hospital, University of Paris Est Créteil (UPEC), Créteil, France; Biomaps, UMR1281, INSERM, Centre National de la Recherche Scientifique (CNRS), Commissariat à l'Energie, Créteil, France., Elypta AB, Stockholm, Sweden., Department of Urology, AOUI Verona, University of Verona, Verona, Italy., Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Departments of Surgery and Surgical Oncology, Division of Urology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada., Department of Diagnostics and Intervention, Urology and Andrology, Umeå University, Umeå, Sweden., Department of Surgery, Section of Urology, University of Calgary, Calgary, Alberta, Canada., Department of Urology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital. Edinburgh, UK; Department of Urology, Western General Hospital, Edinburgh, UK., Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; CRUK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK., The Urology Centre, Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital, London, UK., Department of Urology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Department of Urology, Frimley Health NHS Foundation Trust, Frimley, UK., Department of Urology, Winship Cancer Institute, Emory University, Atlanta, GA, USA., Department of Experimental and Clinical Medicine, University of Florence, Florence Italy; Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, University of Florence, Florence, Italy., Department of Urology and Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden; Elypta AB, Stockholm, Sweden., Department of Urology, The Royal Free London NHS Foundation Trust, London, UK; Division of Surgery and Interventional Science, University College London, London, UK; Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40866172