Evidence is growing for the use of circulating tumour DNA assays in early detection and monitoring of cancers, but three major barriers stand in the way of its adoption in clinical practice, Australian experts believe.
A national workshop of almost 100 oncology researchers and industry representatives held in October 2020 concluded that issues such as establishing clinical utility, standardisation of platforms and most importantly reimbursement of ctDNA assays had to be addressed before ‘liquid biopsies’ could be introduced into routine clinical practice.
The critical issues and potential ways forward to translate liquid biopsies into practice were explored in a paper published in Diagnostics, by Professor Maarten IJzerman of the Victorian Comprehensive Cancer Centre and Professor Sarah-Jane Dawson of the Department of Oncology, Peter MacCallum Cancer Centre.
They noted that half of workshop participants (50%) believed assays would have most immediate impact for monitoring of patient’s response to treatment (eg detection of minimal residual disease, MRD) to inform further treatment decisions, and also for surveillance to detect cancer recurrence. Fewer (41%) believed ctDNA assays were ready for use in early detection of cancer.
Participants believed that tumour-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays would most likely provide better clinical utility than tumour-agnostic assays. But this approach would pose practical challenges and higher costs from the longer turnaround times needed to first obtain tumour tissue samples for sequencing to find candidate somatic mutations for targeted gene panels and ctDNA tracking.
It was noted that in terms of clinical utility, monitoring MRD using ctDNA may be feasible for tumours with a high mutational burden, such as colorectal cancer, melanoma and pancreas cancer, but less feasible in cancers with fewer DNA mutations, such as prostate and breast cancer.
And there were numerous other practical issues identified for routine application of ctDNA assays the workshop noted, such as defining minimum quality standards and performance of testing platforms, and ensuring their use was integrated into current clinical workflows – including how they complemented tissue biopsies and imaging.
And once clinical utility was determined, the more challenging issues of cost effectiveness and reimbursement would come to the fore, the workshop heard. With comprehensive gene panels currently costing up to US$1750 for a single test, a major health economic case would be needed would be for routine implementation, it was noted.
There were also questions about whether ctDNA assays would complement or replace current biomarker assays that are reimbursed, such as EGFR monitoring in NSCLC.
“The diagnostic and treatment landscape is rapidly developing and creating massive challenges for [Health Technology Assessment] agencies making informed and deliberate decisions about which tests to be funded,” the authors wrote.
Participants suggested that alternative payment models may be considered, such as bundled payment per episode of care, or a lump-sum payment for the diagnostic tests for each patient diagnosed with cancer.
“This will leave the actual decisions about which test at what stage at the discretion of the multi-disciplinary team and tumour board,” they said.
But if this was a way forward, it would be critical that tests were available to everyone and incorporated in clinical guidelines to prevent inequity in access, they added.