ctDNA Practical for Early Detection of Relapse, Monitoring Therapy Efficacy in Bladder Cancer

Results from a recent study demonstrate the feasibility of using circulating tumor DNA (ctDNA) assessment for early risk stratification, therapy monitoring, and early relapse detection in patients with bladder cancer (J Clin Oncol. 2019 May 6. Epub ahead of print).

“Novel sensitive methods for early detection of relapse and for monitoring therapeutic efficacy may have a huge impact on risk stratification, treatment, and ultimately outcome for patients with bladder cancer,” Emil Christensen, PhD, Aarhus University Hospital, Denmark, and colleagues said, describing the basis for their study.

“We addressed the prognostic and predictive impact of ultra-deep sequencing of cell-free DNA in patients before and after cystectomy and during chemotherapy,” they continued.

Dr Christensen et al used whole-exome sequencing to identify patient-specific somatic mutations, which were then used to assess ctDNA via ultra-deep sequencing (median, 105,0003) of plasma DNA.

A total of 68 patients with localized advanced bladder cancer were included in the study, along with 656 plasma samples. These samples were obtained at diagnosis, during chemotherapy, before cystectomy, and during surveillance.

According to the findings, at diagnosis (before chemotherapy) the presence of ctDNA was highly prognostic (hazard ratio, 29.1; P = .001).

“After cystectomy, ctDNA analysis correctly identified all patients with metastatic relapse during disease monitoring (100% sensitivity, 98% specificity). A median lead time over radiographic imaging of 96 days was observed,” Dr Christensen and colleagues reported.

The dynamics of ctDNA during chemotherapy was tied to a diseased rate of recurrence in high-risk patients positive for ctDNA before or during therapy (P = .023), whereas pathologic downstaging was not.

Furthermore, analysis of tumor-centric biomarkers demonstrated a link between mutational processes (signature 5) and pathologic downstaging (P = .024). However, the investigators found no significant correlation for tumor subtypes, DNA damage response mutations, and other biomarkers.

“In conclusion, we have found ctDNA testing in patients with bladder cancer who undergo chemotherapy and cystectomy to be highly sensitive and specific for early risk stratification of patients, prediction of treatment response, and early detection of metastatic relapse,” Dr Christensen and colleagues said.

“ctDNA biomarkers are superior to tumor-centric biomarkers (mutations and subtypes) for predicting treatment efficacy, and novel randomized clinical trials should be initiated to determine the clinical impact of ctDNA-stratified therapeutic approaches,” they added.—Hina Khaliq