A liquid biopsy is far more convenient since it is a blood test. It is very easy to get blood and you can see results very quickly since you are not waiting for the biopsy, which includes a lot of processing. You can see results within 1 week.
The problem is that a negative result cannot always be believed. A lot of tumors, particularly those that are restricted to the lung, do not shed their DNA into the blood in a detectable way.
What factors should be taken into consideration for when to rebiopsy patients?
When a decision is made to obtain a rebiopsy, the key question is, “Where to go?” You are looking for a spot that is clearly progressing. It does not help to go to a nonprogressing spot and obtain tissue. That may sound like an obvious point, but we see that happen all the time, mostly because of poor communication. There needs to be a conversation about what you are looking for so that you make sure that the sample is processed in an appropriate fashion.
It is sometimes said that you cannot get molecular results off bone. That is not entirely true. It is possible, but you need to have a conversation with your pathologist to understand what you are looking for and they will tell you how to process it and avoid problems.
What additional factors should one consider when choosing between liquid or tissue-based biopsies?
It depends on what they're asking. If the question is, “What should I do in the frontline setting?” then tissue is preferred if adequate tissue is available. If that tissue is inadequate, it is perfectly reasonable to do a broader liquid test. At that point, a next-generation–based platform might be worth the additional time.
In contrast, I think of this differently at the time of acquired resistance. At that point, you have some time to wait. Usually, patients on targeted therapies are not dramatically progressing in a way that you need to act quickly—making liquid biopsies an option as the first attempt. If you get a positive result, you can go ahead and treat the patient. However, if it is negative, you have to consider that that tumor may not be releasing DNA into the blood in a detectable way. In that case, you can reconsider getting a tissue biopsy.
The balance between acquisition of DNA from a tissue-based pathway and a liquid-based pathway also depends on local resources. If you have an interventional pulmonologist who is happy to progress mediastinal nodes on 1 day’s notice, then it is reasonable to jump to tissue more often because there is less delay. In contrast, if you only have an interventional radiologist who delays things every time you try to get a specimen, then leaning more heavily on liquid biopsies makes more sense.
What are the main takeaways from your presentation?
The advantages of targeted therapy when you find something actionable are so massive that this should extend to patients with a low probability of having those changes. I have found dozens of patients with EGFR
who do not have any of the clinical characteristics that we talk about.
I will never forget a patient that I inherited from an oncologist when he left my institution. She had 3 or 4 biopsies, which all had complications—even though she was a never-smoker. My advice was to go after tissue a fifth time. This was in the pre–liquid biopsy era. She went for it and she had EGFR
mutation that derived dramatic benefit from an EGFR TKI. That is not the average patient. However, there is a massive advantage when you get a molecularly targeted therapy for a patient. In the case of PD-L1, data suggest that 50% of patients will have dramatic clinical improvements with immunotherapy.
What else you would like to highlight?
There are many experimental studies that might further expand these advances. I would like to highlight circulating tumor cell (CTC) capture. The assays that were famous had trouble picking up NSCLC. That has been largely overcome and now, CTCs can be captured in NSCLC. There are ongoing studies trying to look at markers such as PD-L1 in CTCs that I predict will yield fruit.