The use of circulating tumor DNA (ctDNA) as an early detection tool is a promising development. However, the clinical utility of ctDNA in urothelial bladder cancer is not fully understood.

A new paper published by Christensen et al. in the Journal of Clinical Oncology evaluated the use of cell-free DNA as a prognostic and predictive biomarker in urothelial bladder cancer patients. The researchers obtained 656 plasma samples from 68 patient diagnosed with localized muscle-invasive bladder cancer. The ctDNA samples were collected at the time of diagnosis, during and after treatment. The investigators performed ultra-deep sequencing of the plasma samples to monitor the clonal fraction of molecular alterations in ctDNA over time.

The investigators found that the presence of ctDNA was highly prognostic at three different time points, at the time of diagnosis, following chemotherapy and before cystectomy and during disease surveillance. The status of ctDNA at any time point after cystectomy was a stronger predictor than other clinical factors, such as lymph node status before cystectomy and pathologic downstaging. Furthermore, ctDNA analysis detected metastatic relapse with 100% sensitivity and 98% specificity with a median lead time of more than three months over conventional radiographic tools. A significant association between ctDNA dynamics during chemotherapy and tumor recurrence (P = .023) was identified in patients with detectable ctDNA before or during treatment. 

This important study shows the feasibility and clinical utility of ctDNA measurements as a prognostic and predictive tool. Further, prospective validation of these results and integration into randomized clinical trials will be the next steps before routine clinical use.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

Christensen E, Birkenkamp-Demtröder K, Sethi H, Shchegrova S, Salari R, Nordentoft I, Wu HT, Knudsen M, Lamy P, Lindskrog SV, Taber A, Balcioglu M, Vang S, Assaf Z, Sharma S, Tin AS, Srinivasan R, Hafez D, Reinert T, Navarro S, Olson A, Ram R, Dashner S, Rabinowitz M, Billings P, Sigurjonsson S, Andersen CL, Swenerton R, Aleshin A, Zimmermann B, Agerbæk M, Lin CJ, Jensen JB, Dyrskjøt L.“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.” J Clin Oncol. 2019 Jun 20;37(18):1547-1557. doi: 10.1200/JCO.18.02052. Epub 2019 May 6.