Figure 1. Collection of cell-free DNA
The ctDNA fraction (tumor content) is highly variable and it has a clear correlation with proliferative tumor burden. The percent of ctDNA fraction controls the type of alteration that can be detected (figure 2).
Figure 2. The correlation between ctDNA and the type of genetic alteration detected
It has been shown that the detection of ctDNA indicates residual disease. In a study of 68 patients with localized advanced bladder cancer who underwent neoadjuvant chemotherapy and cystectomy, the detection of ctDNA after treatment was an indicative sign of imminent relapse1 (Figure 3). Dr. Wyatt believes this could serve as an excellent opportunity for early intervention and prevention of the consequences associated with disease relapse.
Figure 3. Discovery of ctDNA after treatment – sign of imminent relapse
Dr. Wyatt continued and elaborated on the role of ctDNA in metastatic urothelial carcinoma. The median ctDNA fraction has been shown to be very high in metastatic urothelial carcinoma, with a genomic landscape similar to that of aggressive MIBC. Data have shown concordance between matched tissue and ctDNA in metastatic disease is above 80%.
It is important to understand the significance and limitation of a biomarker negative result. When there is evidence of the absence of ctDNA, we can either say that the tumor is alteration negative and we simply haven’t found it, forcing us to test again or test the tissue instead.
Concluding his talk, Dr. Wyatt summarized a few important take-home messages. First, the detection of ctDNA in the muscle-invasive bladder cancer (MIBC) context informs prognosis. Second, ctDNA is a clinically practical and reliable biomarker source in metastatic urothelial carcinoma. Third, some patients have no/low ctDNA but they, unfortunately, may still have an alteration that we need to discover by utilizing tissue biopsy. Lastly, it is extremely important to incorporate ctDNA into molecularly-guided clinical trials to obtain more data.
Presented by: Alexander Wyatt, PhD, Senior Research Scientist, Vancouver Prostate Centre, Assistant Professor, Department of Urologic Sciences, University of British Columbia, Vancouver, Canada
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, Twitter: @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:
1. Christensen, Emil, Karin Birkenkamp-Demtröder, Himanshu Sethi, Svetlana Shchegrova, Raheleh Salari, Iver Nordentoft, Hsin-Ta Wu et al. "Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma." Journal of Clinical Oncology 37, no. 18 (2019): 1547-1557.