The Evolving Landscape of Molecular Alterations in NSCLC: Optimizing Testing and Treatment to Improve Outcomes - Episode 13

NSCLC: The Role of Liquid Biopsy in Molecular Testing and Treatment Decision-Making

A brief discussion on insufficient tissue results in molecular profiling for NSCLC and how this can be avoided or addressed via liquid biopsy.

John V. Heymach, MD, PhD:
Like all thoracic medical oncologists, I’ve had the frustrating issue arise when a newly diagnosed patient comes in, we send off a biopsy for molecular profiling. The patient comes back 2 weeks later eager to start therapy, and we get the reading that says, “insufficient tissue.” We have to repeat [the molecular profiling], and that’s very frustrating. It’s frustrating for patients. Patients often want to get started right away. In some cases, they may need to get started because they have painful lesions, or they may be really symptomatic from their cancer.

The question is, what to do to avoid insufficient tissue or deal with it? The first thing is to remind whoever is doing the biopsy to get core biopsies and not FNAs [fine-needle aspirations], to make it more likely that you’re going to get adequate tissue. The second possibility is to use liquid biopsies. Liquid biopsies, or sequencing using circulating tumor DNA, get used a couple of different ways. One alternative is to send off a liquid biopsy only if there’s insufficient tissue and a repeat biopsy isn’t feasible. That’s 1 reasonable approach. A second approach is to send off a liquid biopsy in the beginning when you first see the patient. If it gives you a clear-cut answer, you’re done. If it doesn’t give you a clear-cut answer, then send the tissue for sequencing.

A reminder about liquid biopsies: specificity is high, and they have a high positive predictive value. This means that if you get a positive test result, if it tells you KRAS, EGFR,ALK, or 1 of these, you can be confident that alteration is there. But if it’s negative, you can’t be confident that alteration isn’t present. In that case, if you send the liquid biopsy, it doesn’t give you any actionable alteration. Then the recommendation is to send tissue, because the last thing you want to do is miss an actionable alteration that could be treated with an oral medication. That’s the 1 thing I always try to avoid.

The final approach would be to send both assays at 1 time. There are sometimes concerns about whether that gets covered by insurance. If you send both of them at the same time, that’s the safest way to ensure that you get an assay result 1 way or the other. Between the 2, the likelihood is much higher that you’ll get a result, but there’s a possibility that 1 of those assays is redundant. All 3 approaches are certainly possible. My approach is that if I have sufficient tissue in the beginning, and I’m confident I’ll be able to get sequencing done, I send that right away. I send plasma if the test was insufficient. But if I believe somebody may not have sufficient tissue in the beginning, then I’ll send plasma in the beginning and do a rebiopsy only if I don’t get a clear-cut answer from the liquid biopsy. Remember, you need to diagnose cancer by tissue, but when it comes to an actionable alteration, either plasma or tissue is fine for doing the NGS [next-generation sequencing].

Transcript edited for clarity.