1. Eligibility
Using the right test for the right setting
Testing for minimal residual disease or micrometastatic disease needs to be done after completion of surgery or surgery and adjuvant therapy, and then can be continued every several months during surveillance. These tests can be used for monitoring response of unresectable metastatic disease, but this application of the assays is beyond the current scope of MRD utilization.
It is important to use ctDNA tests specific for detecting MRD. There are ctDNA assays for early detection of cancers being developed that will be marketed to patients soon, and there are also existing assays designed for molecular profiling of patients noninvasively. Instead, the assays should be designed for detecting recurrence of disease. The MRD assays, in general, will not provide biomarker status (ie KRAS, NRAS, BRAF mutations), but only a measure of levels of detectable disease.
There are two commercially available assays, Natera Signatera and Guardant Reveal, which are used in this setting. Others are anticipated to be available shortly. We welcome any updates on this and will provide references for any new assays as the information becomes available.
2. Obtaining the Test
Logistics of obtaining the test and reviewing results
These tests are currently conducted as “send out” tests and are not run in your oncologist’s hospital. This requires a bit of extra coordination with your team in drawing the blood in specially designed tubes provided by the company and then mailed in the provided kits. For some of the tumor-informed assays, there is a need to separately send tissue from your surgery to be sequenced. The providing company will usually take care of requesting this for you. The results can take from 2 weeks to 6 weeks to return.
3. Interpreting Results
How to make sense of the test results
The results are returned in different ways by different providers. Most will either provide a yes / no that MRD was detected, while others will also quantify the amount as the mean tumor molecules per mL (MTM/mL), where anything that is able to be quantified is considered positive or present.
The current commercial tests have very low false positives (and therefore a high positive predictive value) meaning that if ctDNA is detected, there is a very high chance that there are tumor cells in the body. The sensitivity (ability to detect the cancer if it is still present) is around 50-70%, but with serial testing (every 3 months) then the sensitivity is much higher and closer to 80-90%. Currently we do not know that any of the available tests are better than another.
4. Act on the Results
How to Use These Results Remains an Area of Research
This is something to think about before ordering the test…. How will my doctor use these results to provide better care and outcomes? At the moment, it can be used to help understand the risk of recurrence, but it is not clear that anything beyond surgery and adjuvant therapy can improve outcomes. Specifically, it is not clear that starting any additional chemotherapy is helpful–indeed studies of irinotecan for example suggest no benefit from this approach. We encourage being proactive and exploring clinical trials with novel therapies.