Background Despite the increasing treatments options, reliable biomarkers of response are still missing for patients affected by metastatic renal cell carcinoma (mRCC).
Methods Patients affected by mRCC undergoing standard first line treatment were enrolled. Twelve ml of blood were drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) analyses were performed on cfDNA using the Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy.
Results A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/µl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p=0.001 and p=0.008, respectively). cfDNA amount was also correlated with best response (p=0.006). A further cfDNA cut-point divided patients into short, intermediate and long responders, with a PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p<0.001). PFS resulted to be shorter in carriers of mutant TP53 compared to not carriers with a p=0.04. Patients with high cfDNA levels and TP53 mutant have the worst PFS, and patients with low cfDNA and no mutations in TP53 have the longer PFS (p=0.004).
Conclusions The present study demonstrates that cfDNA and TP53 may be used as predictive biomarkers of response in mRCC.