Novel Predictive Biomarkers for Non-Small Cell Lung Cancer - Episode 4

Molecular Testing Through Multiple Labs in NSCLC


Greg Riedlinger, MD, PhD: There’s a challenge in non—small cell lung cancer, specifically with the number of tests that are required and the splitting of samples. We encounter this in other areas of pathology as well, but it’s becoming somewhat more problematic specifically in non–small cell lung cancer because there are requests for NGS [next-generation sequencing] testing, FISH [fluorescence in situ hybridization] testing, as well as PD-L1 [programmed-cell death ligand 1] testing often. It requires good use of a limited amount of material to make sure that you have adequate tissue to perform all of these tests and properly use the limited amount of tissue that we have.

Currently, I think a lot of the places, based on NCCN [National Comprehensive Cancer Network] guidelines, are testing for EGFR and then ALK and ROS. Often, ALK and ROS are tested by FISH. But now, there are more and more NGS panels, smaller NGS panels especially, which are able to detect not only the single nucleotide variants and small insertion deletions, but also rearrangements and copy number changes. Some of these other targets that have traditionally been sent for FISH testing can also be picked up. At least in Rutgers Cancer Institute, it’s not so much an issue with turnaround time because these tests are done as they’re ordered, but it’s more an issue of making sure that we have adequate tissue to perform all these tests.

Jared Weiss, MD: Patients, and even many doctors, don’t realize how vulcanized our laboratories are. A surgical pathology laboratory is typically separate from the laboratory that might be doing molecular testing, which in many cases is going to be separate from the laboratory doing other kinds of testing like cytogenetics or FISH. I think a lot of outsiders don’t really appreciate how separate these entities are from one another and how it can influence what we as clinicians get from our specimens. This comes back to the issue of tissue stewardship and the need for good communication, specifically around what the tissue obtained is to be used for. When tissue is divided, you can increase the turnaround time.

There’s a lot of processing and administrative steps required here. You can also use tissue in ways that don’t answer questions of utility to the clinician. There’s really 1 major answer to these obstacles, which is communication. Communication starts prior to the biopsy. It needs to continue with all the information regarding what’s to be done on the requisition. It needs to be the first level of communication between the medical practitioner, the oncologist, the pathologist, and the person obtaining the biopsy. But then, there needs to be inter-laboratory communication to ensure that this good tissue stewardship of precious material continues. What that means is if we’re pretty sure this is lung cancer—we have a spiculated lung nodule, mediastinal adenopathy, and an adrenal met in a patient who has smoked quite a bit screaming, “I am lung cancer!”—then that communication can ensure that the surgical pathology laboratory isn’t using up the tissue proving, for example, that this isn’t prostate cancer.

Despite all of that, we don’t always end up with everything that we need and the question of if we should rebiopsy is quite common. In the case of adenocarcinoma of the lung, or really any nonsquamous lung cancer, if tissue is not adequate for molecular characterization, it is absolutely mandatory to rebiopsy. As we enter an era of immunotherapy, I think there is some controversy about when to rebiopsy for PD-L1. When these drugs were mostly to be used in the second line and when there was a drug available regardless of the PD-L1 status, I wasn’t advocating for repeat biopsy if tissue was inadequate. In the last year though, we’ve had a flurry of publications and presentations about moving these agents into the front line. While there’s a lot of controversy about exactly who should get what, one theme that clearly emerges is that we’re using PD-L1 to help determine what patients get in the front line. In that context, I think it is worth the rebiopsy if PD-L1 status is not available.

Transcript Edited for Clarity