Clinical Utility of Cell-free and Circulating Tumor DNA in Kidney and Bladder Cancer: A Critical Review of Current Literature

Abstract

Context: Bladder and kidney cancers require invasive procedures for definitive diagnosis, and bladder cancer requires repeated procedures to monitor for disease recurrence. Given the recent work to identify molecular alterations in liquid biopsies to diagnose and monitor these diseases, a synthesis of the growing body of evidence is merited. Objective: To review current data on cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) and to synthesize their roles in the diagnosis, monitoring, and prognostication of bladder and kidney cancer. Evidence acquisition: A literature review was conducted through August 15, 2020 including prospective and retrospective studies. Keywords included "cell-free DNA", "circulating tumor DNA", "kidney cancer", "renal cell carcinoma", "bladder cancer", "upper tract urothelial carcinoma", and "urothelial carcinoma". Evidence synthesis: Urine tumor DNA (utDNA) has sensitivity of 91% and specificity of 96% for detecting bladder cancer, outperforming cystoscopy and cytology. Increased utDNA and ctDNA are associated with progression from non-muscleinvasive to muscle-invasive disease. In patients undergoing cystectomy, ctDNA detection is associated with worse overall survival and disease recurrence, and with persistent tumor on surgical pathology in those who received neoadjuvant chemotherapy. cfDNA is significantly higher in patients with kidney cancer than in healthy controls or in those with benign lesions, and detectable ctDNA and increased cfDNA are associated with decreased survival. Conclusions: Combined data from small studies provide evidence that cfDNA and ctDNA may have the ability to detect, monitor, and prognosticate in patients with bladder, upper tract urothelial, and kidney cancers.

Circle‐Seq reveals genomic and disease‐specific hallmarks in urinary cell‐free extrachromosomal circular DNAs

“…In addition, previous studies of the fragmentation patterns, copy number aberration, DNA mutation, methylation, integrity and concentrations of urinary cfDNA revealed that urinary cfDNA has emerged as an informative biomarker for prenatal screening, organ transplantation monitoring and infectious/urological malignant disease diagnosis. 3 , 8 , 9 , 10 , 11 , 12 , 13 …”

The Role of Circulating Biomarkers in the Oncological Management of Metastatic Renal Cell Carcinoma: Where Do We Stand Now?

“…The role of ctDNA to predict and monitor treatment response in kidney cancer has also been evaluated [ 90 ]. In a recent study, genomic alterations in ctDNA were evaluated in 220 patients with metastatic RCC.…”

Liquid biopsy zur Individualisierung der Therapie beim fortgeschrittenen Harnblasenkarzinom

“…Letztlich unterliegen Primärtumore und Metastasen bedingt durch verschiedene Therapien einer klonalen Evolution. Publizierte Diskrepanzen zwischen Primärtumor und ctDNA sind darüber hinaus durch unterschiedliche Plattformen, die für die Sequenzierung verwendet wurden, verursacht, sodass ein direkter Vergleich nur bedingt möglich ist [9]. Dagegen sequenzierten Vandekerhove et al 265 Gene in gematchten Tumorgeweben und ctDNA von 46 metastasierten Patienten auf derselben Plattform [10].…”

“…In Abhängigkeit von den Plattformen und Genpanels wurde in 73-90% der Patienten mit metastasierten Urothelkarzino-men ctDNA durch NGS nachgewiesen [9]. Dagegen war die Rate bei Patienten mit organbegrenzten Tumoren wesentlich niedriger (14%) [11].…”