Part 1: Barriers to Rapid Molecular Testing for Early-Stage Lung Cancer

Aaron E. Lisberg, MD (Moderator)

Thoracic Medical Oncologist

Assistant Clinical Professor, Medicine

UCLA School of Medicine

Los Angeles, California

CASE SUMMARY

An otherwise healthy 60-year-old White woman presented with a nonproductive cough. She was a former smoker who quit 8 years ago (13 pack-years). She had an ECOG performance score of 0, blood pressure 120/93, heart rate of 75, body mass index of 22, and lungs were clear to auscultation bilaterally. All laboratory results were within normal limits. A chest X-ray revealed a 5.5-cm right mass in the right upper lobe of the lung, while a CT chest/abdomen scan showed a lobulated 5.5 x 5.1-cm mass in the right upper lobe.

A biopsy of the right upper lobe revealed thyroid transcription factor-1-positive adenocarcinoma consistent with non–small cell lung cancer (NSCLC). PET imaging was negative for any spread to lymph nodes or distant metastasis. A brain MRI was negative and pulmonary function tests were normal.

The patient underwent a right upper lobectomy without complications. Her pathology was a 5.5-cm tumor with negative margins, 0 nodes positive for malignancy, and a pathologic stage IIB* (pT3N0M0) lung adenocarcinoma. Her performance status was now 1.

DISCUSSION QUESTIONS:

• What are the challenges and barriers to testing?​
• Who on the multidisciplinary team orders molecular testing?​

AARON E. LISBERG, MD: What are the challenges and barriers to testing, and who on the multidisciplinary team orders molecular testing? So, can someone please share with us? Maybe someone who is testing for molecular testing in the frontline setting? What challenges or barriers have they had, in terms of doing the testing, and then if we can also get a sense for who on the multidisciplinary is ordering molecular testing.

VEENA CHARU, MD: I don’t find many challenges to ordering the molecular testing. I usually send it for next-generation sequencing [NGS], and I am the one who’s ordering and telling the pathologist to send it. It’s not automatically done by pathologists. Once I see the patient, then I have to call them and ask them to send the specimen.

CANNON MILANI, MD: In general, the oncologist is the one performing the testing, and I don’t necessarily see it as a barrier or challenge. I think it’s more of a timing matter, in terms of receipt of the result. I think that that would be the biggest challenge. So, for our multidisciplinary team, because we engage in subspecialization now at Kaiser Permanente West Los Angeles, it’s the oncologist that is performing the testing.

LISBERG: Are you having significant delay that really affects the way you manage patients? What’s your typical turnaround time for these types of tests?

MILANI: With immunohistochemistry, it’s a little easier, but I would say 1 to 2 weeks. I think it would be nice to have all this information when the patient comes in for the initial consultation. Patients are quite savvy now, and I even have patients who have the patient version of the NCCN [National Comprehensive Cancer Network] guidelines on their first visit. They’re very data-driven, some of them, and so they expect to have that on initial receipt of post-surgery, and even biopsy. It’s a confidence-building measure for patients to see the oncologist have that applicability of information on their first visit with them. So, I think it’s more those particular barriers or challenges, as opposed to getting the testing ordered, per se.

LISBERG: What kind of testing panel are you sending?

MILANI: We use NeoGenomics Laboratories, and either Strata Oncology or Tempus, and liquid biopsy when required, as well.

LISBERG: Dr Sweet, what are you doing at your institution?

THOMAS SWEET, MD: Part of this discussion makes me think how different lung cancer is. Our pathologists have always been resistant, except for breast cancer, to do the molecular testing as part of the routine pathology workup. And part of this discussion makes me think that we’ve reached a point in time where this should be done. Historically, they’ve been resistant for a variety of reasons, especially because they didn’t know if the patient was metastatic or not.

But, for the majority of patients now, if knowing all of these markers are critical to even early-stage management, I think that the pathologists should do this as an automatic routine. It would save time, because usually it has to be implemented by myself or perhaps we do have a nurse who is aware of the patients with lung cancer as they come down the pike. The nurse may get that ball rolling before we see the patient.It’s an interesting question. Why doesn’t the pathologist do it?

LISBERG: How much time do you think is added on because the pathologist isn’t doing it reflexively, in your system?

SWEET: It varies. It could be a good week to 2 weeks. And as previously mentioned, it disrupts the patient’s confidence when you meet the patient and you say, “Well, there’s more information that I need. We have to wait.” Yet, there’s this other dynamic in our system to get that patient seen as soon as possible, even in advance of having all the detailed information on the back end. So, I’ve long been an advocate of pushing pathology to do this reflexively in many of the diseases, generally without success.

LISBERG: Even in my system, I have some of the same challenges. Why do you think things haven’t changed, or what is the rationale from pathology for not doing these things up front?

SWEET: Well, historically, I think the rationale is that we were generally looking at markers for advanced disease.They didn’t know who was advanced and who wasn’t. They could spend some time looking at the clinical picture, but they prefer not to. They just want to look at the specimen.

But you could argue, then, if a lung specimen comes in, it should be reflexively assessed for all of these known markers. We’ve been doing it in breast cancer for 40 years. They rapidly adopted HER2 as a standard, and as we’re learning, we’re going to see other standards that involve biomarker-driven or genetically-driven treatments, even in early-stage disease.

LISBERG: I agree with everything you’re saying. Clearly, EGFR testing is critical because it changes our management. You could argue whether some of the other molecular testing is critical in the early stage, but I agree with you. Those trials are ongoing, and we anticipate potentially that those could be practice changing.

NILESH VORA, MD: I think the only thing I’d add to this is we’ve made a concerted effort to meet with our pathologist and share the early-stage data with them; combine that with the conversations we had in the past about advanced diseases and how important it was to have the molecular testing. The rule now is to have all lung cancer specimens sent out for NGS automatically. We’re using Tempus as the platform, and we’ve talked to Tempus and had them come to meet with our pathologist, and it’s a good system setup.

I can recall having a patient who was diagnosed in an outside hospital, and they didn’t do reflexive testing on lung cancer specimens, and there was a significant delay in treatment, even with the patient having advanced stage disease. I believe the thinking from that hospital was, they got burned once when they sent or ran these tests, and it didn’t get used or the patient ended up not getting treatment, and so they are very cost conscious on this thing and are waiting for the order before they send off these tests.

Those are the only challenges. I would add that I feel like in the early-stage venue of lung cancer, we have the time to wait a little bit, based on the EGFR testing, because some of these patients are getting adjuvant chemotherapy. As long as I get the results after 3 to 4 months, I feel comfortable, and I don’t think there’s much delay in treatment in those cases.