January 3, 2018

Next-Generation Sequencing of Tumor Tissue Versus Blood in Patients with Advanced Urothelial Cancer

Study examines concordance between commercially available genomic tests


By Pedro Barata, MD, MSc, Brian Rini, MD, Jorge Garcia, MD, Pauline Funchain, MD, and Petros Grivas, MD, PhD


Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

The ability to sequence DNA in cancer cells has helped identify unique molecular alterations, for which there are an increasing number of potential therapies that merit evaluation. Multiple next-generation sequencing (NGS) platforms are now available, but little is known about the concordance of genomic alterations between different tests, especially when different samples, e.g., tumor tissue or circulating tumor DNA (ctDNA), are used.

In our paper titled “Next-generation sequencing in cell-free circulating tumor DNA and tumor tissue in patients with advanced bladder cancer: a feasibility pilot assessment,” published recently in Annals of Oncology, we aimed to assess the concordance of genomic alterations found in two frequently used commercially available NGS assays either in blood (“liquid biopsy”, Guardant360™) or tumor tissue (FoundationOne™), in consecutive patients seen at Cleveland Clinic with advanced urothelial cancer. In our cohort, both tests were able to detect a relatively high number of genomic alterations; however, only a relatively small proportion suggested potential therapies that could be attempted. Furthermore, we found a significant discordance (> 80 percent) between the two tests, even when both tumor tissue and circulating tumor DNA were collected around the same time (which was the case in a small number of patients).

Complementary but not interchangeable

This study is one of the first to calculate concordance between NGS tests in advanced urothelial cancer while the same concept has been reported in other cancers with higher concordance rates (e.g., lung and breast cancers). There are several reasons that may explain the low concordance reported, including intra- and intertumoral heterogeneity, different assays and bioinformatics used, intervening therapies and timing of specimen collection. This low concordance suggests that while these NGS platforms may provide complementary and not interchangeable information, the integration of the data into clinical practice remains challenging, especially in the broader oncologic community. Because of this, multidisciplinary genomics tumor boards that discuss in detail NGS reports become much more frequent. Until recently, archival tumor tissue NGS was the most commonly used genomic test for clinical trial eligibility, as it has been commercially available for longer and generally has included a broader panel of genes tested. Nonetheless, “liquid biopsies” are technically and logistically easier, faster, less invasive, and may be used in a dynamic serial manner to assess resistance mechanisms, treatment response and clonal evolution.


While the number of genomic platforms is rising and we have more genomic-driven biomarker-based clinical trials, further analysis can help data interpretation and optimize clinical applications. The many ongoing prospective clinical trials that incorporate NGS screening (and possibly monitoring) in their design will likely help us better understand the results and ultimately may contribute to more available therapies for our patients.

Dr. Barata is a medical oncologist and experimental therapeutics fellow at Cleveland Clinic Cancer Center. Dr. Rini directs the Cancer Center’s Genitourinary Cancer Program. Dr. Garcia is staff in the Department of Hematology and Medical Oncology. Dr. Funchain is associate staff in the Department of Hematology and Medical Oncology.

Related Articles

Physician with patient
February 21, 2024
Strategies for Improving Clinical Trial Equity

Cleveland Clinic Cancer Institute takes multi-faceted approach to increasing clinical trial access

How antibody drug conjugates work
February 13, 2024
Real-World Use of Trastuzumab Deruxtecan

Key learnings from DESTINY trials

February 1, 2024
Possibilities of CRISPR Technology (Podcast)

Gene editing technology offers promise for treating multiple myeloma and other hematologic malignancies, as well as solid tumors

Disparities in multiple myeloma
January 25, 2024
Major Study Identifies Global Disparities in Drug Toxicity for Multiple Myeloma Treatment

Study of 401,576 patients reveals differences in cancer burdens as well as overall survival

Dr. Shilpa Gupta
December 27, 2023
A New Standard Emerges in Advanced Urothelial Carcinoma After Decades of First-Line Chemotherapy

Enfortumab plus pembrolizumab reduced risk of death by 53% compared with platinum-based chemotherapy

23-CNR-4318382-CQD-Hero-650×450 Dr Hill
December 19, 2023
Active Surveillance may be a Feasible Option for a Subset of Patients with Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Large cohort study finds no reduction in survival for patients managed with active surveillance compared to treated patients

Dr. Caimi
December 15, 2023
CAR-T Cell Therapy Effective in Refractory Double-Hit/Triple-Hit Lymphoma

Two thirds of patients responded to CAR T-cell therapy

23-CNR-4344308-CQD-Hero-650×450 Ornstein
December 14, 2023
Belzutifan Shows Improvement in Progression-Free Survival for Patients with Refractory Clear-Cell Kidney Cancer

Belzutifan superior to everolimus in phase 3 clinical trial