SuPARnostic: An Advanced Predictive Tool for Detecting Recurrence in Renal Cell Carcinoma - European Medical Journal

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SuPARnostic: An Advanced Predictive Tool for Detecting Recurrence in Renal Cell Carcinoma

2 Mins
Urology
EMJ Urology 11.1 2023 feature image
Authors:
*Nessn H. Azawi,1,2 Karina Sif Søndergaard Mosholt,1 Nathalie Demuth Fryd,3 Lars Lund,1,2 Juan Ignacio Brignone,5 Nanna Hvid,3 Helle Wulf Johansson,6 Ole Birger Vesterager Pedersen,6 Susanne Gjørup Sækmose,6 Saeed Dabestani7,8
  • 1. Department of Urology, Zealand University Hospital, Roskilde, Denmark
  • 2. Institute of Clinical Medicine, University of Copenhagen, Denmark
  • 3. Department of Urology, Aarhus University Hospital, Denmark
  • 4. Department of Urology, Odense University Hospital, Denmark
  • 5. Department of Urology, Aalborg University Hospital, Denmark
  • 6. Department of Clinical Immunology, Næstved Hospital, Denmark
  • 7. Department of Urology, Kristianstad Central Hospital, Lund, Sweden
  • 8. Department of Translational Medicine, Division of Urological Cancers, Lund University, Sweden
*Correspondence to [email protected]
Disclosure:

The authors have declared no conflicts of interest.

Citation:
EMJ Urol. ;11[1]:39-40. DOI/10.33590/emjurol/10307275. https://doi.org/10.33590/emjurol/10307275.
Keywords:
Biomarker, clear cell kidney cancer, liquid biopsy, prognostication, recurrence-free survival.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

BACKGROUND AND AIMS

Renal cell carcinoma (RCC) is the most common malignant kidney tumour, with clear cell RCC (ccRCC) accounting for 70–80% of all cases.1 Approximately 15–20% of patients have primary metastatic RCC at diagnosis, and 15–20% of those who receive curative treatment for localised tumours will experience recurrence within 5 years of follow-up.2 Despite standard radiological imaging follow-up protocols, 30% of recurrences are found outside these protocols, and only 10% of patients with recurrent disease have curable tumours.3,4 The search for prognostic biomarkers in RCC has led to investigations of the soluble urokinase-type plasminogen activator receptor (suPAR), a non-specific marker of systemic inflammation.5,6 suPAR has been associated with detection and survival in various diseases, including RCC.7-9 In this study, the authors’ aim was to investigate the prognostic accuracy of pre-operative plasma suPAR in predicting recurrence and survival in patients who received curative intent treatment for localised ccRCC. The authors hypothesised that an elevated pre-operative suPAR would be correlated with poorer overall survival and recurrence-free survival.

MATERIALS AND METHODS

Plasma from 235 patients with pathologically confirmed ccRCC and stored in a Danish National Biobank were identified for this study. Demographic and pathological data were extracted from patients’ electronic medical records. The level of suPAR, along with other factors such as age, gender, method of treatment, T-stage, Fuhrman grade, Charlson Comorbidity Index (CCI) score, presence of hypertension, level of C-reactive protein, level of haemoglobin, and presence of symptoms were analysed. The concentration of suPAR was measured using the commercial suPARnostic® (ViroGates, Birkerød, Denmark) assay kit and analysed through spectrophotometry. Descriptive statistics and the area under the curve operator were used to indicate the overall performance of the diagnostic test of suPAR. Analyses were performed using MedCalc® Statistical Software (MedCalc, Ostend, Belgium).

RESULTS

This study included 235 patients with ccRCC. The analysis showed that pre-operative plasma suPAR levels of ≥6 ng/mL were significant negative predictors of both overall survival (hazard ratio: 1.69; 95% confidence interval [CI]: 0.99–2.89; p=0.050) and recurrence-free survival (hazard ratio: 1.91; 95% CI: 1.03–3.57; p=0.041) (Figure 1). Furthermore, suPAR levels of ≥6 ng/mL remained a negative predictor of overall survival in multiple regression analyses (odds ratio: 5.18; 95% CI: 1.50–17.93; p=0.009). The prognostic performance of suPAR was 0.576, and adding suPAR measurements did not significantly improve the diagnostic accuracy of the Leibovich scoring system, but the combination of suPAR and T-stage had the same diagnostic performance as the Leibovich scoring system alone (area under the curve: 0.735). These findings suggest that pre-operative plasma suPAR may be a useful prognostic biomarker in predicting recurrence and survival outcomes in patients with ccRCC.

Figure 1: The overall survival and recurrence-free survival rate for patients with (A) high and (B)
low soluble urokinase-type plasminogen activator receptor.
SuPAR: soluble urokinase-type plasminogen activator receptor.

CONCLUSION

This study highlights the importance of measuring suPAR as a predictive tool in the progression of RCC, identifying a two-fold difference in recurrence risk when circulating suPAR exceeds 6 ng/mL. When adjusted for the most relevant clinical and histological parameters associated with RCC, this showed for the first time that pre-operative plasma suPAR has the potential of being prognostic for recurrence and overall survival. Pending external prospective validation and standardisation, the authors see promise in suPAR as a liquid biomarker for RCC.

References
Brierley JD et al., "Renal Pelvis and Ureter", TNM Classification of Malignant Tumours, 8th edition, Wiley-Blackwell, pp.202-3. Patard JJ et al. Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. J Clin Oncol. 2005;23(12):2763-71. Dabestani S et al. Intensive imaging-based follow-up of surgically treated localised renal cell carcinoma does not improve post-recurrence survival: results from a European multicentre database (RECUR). Eur Urol. 2019;75(2):261-4. Dabestani S et al. Long-term outcomes of follow-up for initially localised clear cell renal cell carcinoma: RECUR database analysis. Eur Urol Focus. 2019;5(5):857-66. Gatto F et al. Plasma glycosaminoglycans as diagnostic and prognostic biomarkers in surgically treated renal cell carcinoma. Eur Urol Oncol. 2018;1(5):364-77. Sabatino M et al. Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy. J Clin Oncol. 2009;27(16):2645-52. Chounta A et al. Serum soluble urokinase plasminogen activator receptor as a screening test for the early diagnosis of hepatocellular carcinoma. Liver Int. 2015;35(2):601-7. Dohn LH et al. uPAR expression pattern in patients with urothelial carcinoma of the bladder – possible clinical implications. PLoS ONE. 2015;10(8):e0135824. Illemann M et al.; Danish Study Group on Early Detection of Colorectal Cancer. Urokinase-type plasminogen activator receptor (uPAR) on tumor-associated macrophages is a marker of poor prognosis in colorectal cancer. Cancer Med. 2014;3(4):855-64.

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