REVIEW
Liquid biopsy in Renal Cell Carcinoma: Current and future applications Alessia Cimadamore 1, Simone Scarcella 2, Erika Palagonia 2, Lucio Dell’Atti 2, Andrea Benedetto Galosi 2, Rodolfo Montironi 1. 1
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy; 2Department of Urology, Marche Polytechnic University, School of Medicine, United Hospitals, Ancona, Italy.
Renal cell carcinoma (RCC) is the seventh most common cancer and the most lethal urological malignancy with 5‐year overall survival of 74%, that decrease to 8% in patients with evidence of distant metastasis upon initial diagnosis. To date, no serum or urine biomarkers are currently available for early diagnosis, for monitoring recurrence and response to therapy. Liquid biopsy is a non-invasive diagnostic assay that can detect tumor molecular alterations at diagnosis, after surgery and during progression. Liquid biopsy includes testing for circulating tumor nucleic acids (DNA and RNA), circulating tumor cells (CTC) and small vesicles. In this paper, we reviewed the current knowledge on circulating tumor DNA and CTC in RCC, focusing on the newly developed and promising techniques, such as the circulating free-DNA methylation analysis, and their potential applications in the future.
SUMMARY
KEY WORDS: Renal cell carcinoma, kidney tumors, liquid biopsy, circulating tumor cells, circulating DNA, biomarkers.
INTRODUCTION
LIQUID
Renal cell carcinoma (RCC) is the seventh most common cancer and the most lethal urological malignancy with 5‐year overall survival of 74%, that decrease to 8% in patients with evidence of distant metastasis upon initial diagnosis (1). Around 30% of patients have metastases detected at preoperative screening or surgery, termed synchronous metastases. Up to 50% develop metastases after the removal of the primary tumor (at least 3 months and as late as 30 years after primary surgery), called metachronous metastases. The timing and location of metastases in RCC are difficult to predict, which makes surveillance challenging (2). At present, radiological assessments of renal masses and metastases are insufficient for qualitative characterization of the tumor. Histopathological evaluation is needed for diagnosis, grading and staging of primary tumors; however, in the setting of metastatic disease, no serum or urine biomarkers are currently available to monitor recurrence and response to therapy. During the last decade, multiple genetic alterations of RCC have been associated with prognosis and response to therapy, even though no specific mutations have been associated with sensitivity or resistance to a specific drug.
Liquid biopsy consists in a liquid sample such as whole blood/plasma/urine used for identifying molecular circulating signatures shared with solid tumors. In other words, it can be considered a surrogate material of tissue/cytological sample and can be used as a non-invasive test that allows multiple serial sampling at any stage of disease (3) (Figure 1). Liquid biopsy has been proposed as a potential strategy to improved stratification of patients for adjuvant therapy trials (4, 5). The main goal of liquid biopsy in this scenario would be the detection of minimal residual disease following intended curative nephrectomy. In other malignancies such as lung cancer, colon cancer, breast cancer and prostate cancer, the development of circulating tumor DNA (ctDNA) assays is intended to evaluate of the presence of specific genetic alterations able to predict response to targeted therapy. Contrariwise, in the therapeutic scenario of RCC there is no predictive biomarker able to select patient for a specific therapy. As consequence, many of the studies published in the literature have focused on the quantification of ctDNA and CTCs as measures of tumor burden and on its correlation with prognosis and development of metastasis (6, 7).
BIOPSY IN RENAL CELL CARCINOMA
Advances in Urological Diagnosis and Imaging - 2021; 4,3
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