ctDNA Feasible, Accurately Detects Genomic Alterations in Metastatic RCC

A study including the largest cohort of patients with metastatic renal cell carcinoma (mRCC) to date has shown that circulating tumor DNA (ctDNA) testing is viable and efficient for detecting genomic alterations (GAs) in this patient population (Ann Oncol. 2020;31[suppl_4]:S550-S550).

“ctDNA analysis is a non-invasive method used to assess tumor-derived [GAs]. Previous work in mRCC has shown that ctDNA profiles evolve with treatment in mRCC. We utilized a commercially available ctDNA assay to identify common GAs in mRCC and compared ctDNA and tissue-based GAs in patients with mRCC,” wrote Zeynep B. Zengin, MD, Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, and colleagues.

Between November 2016 and December 2019, the researchers identified 847 consecutive patients with mRCC who underwent ctDNA testing via a clinically validated 73- to 74-gene panel. An analysis of sequence alterations, small insertions/deletions, amplifications, and fusions were analyzed in the targeted next-generation sequencing (NGS).

Furthermore, GAs identified with ctDNA were compared to GAs detected via tissue-based platforms in a subset of patients using either whole-exome sequencing or targeted NGS. Variants of unknown significance were included in tissue test results as clinically relevant alterations were classified as such.

Amongst all patients, ≥1 GA was detected in 669 (72%) of 929 ctDNA samples, with TP53 (37%), VHL (22%), and EGFR (6%) were the most frequently altered genes in ctDNA (excluding variants of unknown significance and similar variants). The most frequent mutations were in VHL (63.8%), PBRM1 (44.7%), and SETD2 (31.9%), the latter 2 genes were not included in the ctDNA assay; tissue DNA analysis of 47 points were also assessed.

After limiting to only the genes included on the ctDNA assay, a total of 154 GAs were found across both assays. Of the 154, 41 (26.2%) GAs were exclusive to blood, while 92 (59.7%) were exclusive to tissue, and 21 (13.6%) were found in both.

The median time between tissue and ctDNA assays was 15.3 months; the cumulative concordance rate between ctDNA and tissue DNA samples was 96.6%.

“Our study shows ctDNA analysis is feasible and highly concordant with tissue genomic analysis. Exclusive GAs found on both platforms suggests tumor evolution over time and treatment, which may assist in guiding treatment selection in mRCC,” concluded Dr Zengin et al.—Alexandra Graziano