Reflex NGS and PD-L1 Testing Streamlines Biomarker Turnaround and Treatment Planning in Resectable NSCLC

In this interview, Tina B. Edmonston, MD, and David D. Shersher, MD, from Cooper Medical School at Rowan University, review findings from their study, “Implementation of a next-generation sequencing and PD-L1 immunohistochemistry reflex testing protocol for non-small cell lung cancers improves turnaround time,” focusing on how earlier access to next generation sequencing (NGS) and programmed death-ligand 1 (PD-L1) results can streamline multidisciplinary decision-making and support timely neoadjuvant and adjuvant treatment planning.

Key Takeaways:

• Molecular results (NGS, PD-L1) are now central to neoadjuvant protocol systemic therapy selection; delays in testing delay treatment initiation compared with prior upfront-surgery pathways.
• Pathologist-initiated reflex PD-L1 and lung cancer NGS at diagnosis (approved by medical executive committee) reduced median procedure-to-result TAT by 2 days (20 days total); cytology cell blocks by 3 days (19 days total).
• Typical 10- to 14-day molecular profiling delays challenge tumor board decisions (surgery vs systemic therapy); reflex testing reduces ordering/processing delays and supports timely sequencing across thoracic surgery, medical oncology, radiation oncology, pathology, and pulmonology.

Please introduce yourself by stating your name, title, organization, and relevant professional experience.

Tina B. Edmonston, MD: My name is Tina B. Edmonston and I am the director of the Molecular Pathology Laboratory at Cooper University Health Care and a professor of pathology at Cooper Medical School at Rowan University. One of the important roles of our lab is assessment of molecular biomarkers for malignancies that inform targeted treatment for cancer patients. Our lab started NGS for solid tumors in 2019.

David D. Shersher, MD: My name is David D. Shersher and I am the head of the Division of Thoracic Surgery at Cooper University Health Care and an associate professor of surgery at Cooper Medical School at Rowan University. I co-lead the thoracic oncology service line with my medical oncology counterpart Polina Khrizman, MD. We work with a wonderful group of multidisciplinary collaborators as part of a busy thoracic oncology practice at Cooper MD Anderson. 

How does reducing the turnaround time for reflex biomarker testing meaningfully impact treatment selection and sequencing for patients with resectable NSCLC, particularly in the neoadjuvant and adjuvant settings?

Dr Shersher: The normal clinical pathway entails evaluating the patient, waiting for the patient to undergo biopsy and staging studies (eg, PET/CT, MRI brain at times), and ultimately undergoing presentation at a multidisciplinary tumor board conference.  Oftentimes, the pathology report is given to the ordering physician and there is a delay in the medical or surgical oncologist receiving and ordering molecular testing. In today’s world, we consider all stage 2 and above patients with lung cancer for neoadjuvant protocol systemic therapies. This is a change from previous practice, in which most patients underwent up front surgery and rapid molecular testing was not as important. This consideration heavily relies on molecular marker results (eg, NGS, PDL-1), and any delays will ultimately delay initiation of treatment for the patient. Reducing turnaround time for reflex biomarker testing absolutely impacts these real-world delays.

What operational or workflow changes were most critical to successfully integrating reflex NGS and PD-L1 testing into the clinical pathway for stage 1B and higher NSCLC?

Dr Edmonston: In collaboration with the thoracic oncology team and based on National Comprehensive Cancer Network (NCCN) guidelines, we established a reflex testing protocol that allows the pathologist to initiate PD-L1 and lung cancer NGS testing on all non-equivocal non–small cell lung cancers of clinical stage 1B and above as soon as they make the diagnosis, rather than waiting for a clinician to order the tests. The reflex protocol was approved by the medical executive committee in order to avoid violation of Starck laws of self-referral within the institution. Empowering the pathologists to initiate biomarker testing at the time of diagnosis helped our institution to reduce the turnaround time (TAT) from procedure to biomarker result by a median of 2 days (20 days total), and even more for cytology cell blocks, where the median overall TAT was reduced by 3 days (19 days total), due to faster pathology sign-out before the biomarker reflex was triggered.

The most impactful workflow improvements were the following:

• Reducing the time it takes for oncologists to see the pathology report, review the patient history to determine clinical necessity, and place the order.
• Shortening time required for the pathology department to process the order by eliminating the need to pull slides and blocks again for processing.

Our institution already had a policy in place where the pathologist contacted the treating physician with each new diagnosis, but it is conceivable that the time between diagnosis and initiation of biomarker testing could be significantly longer, especially if an oncologist has not been determined for a patient.

From a clinician’s perspective, how do delays in biomarker results affect multidisciplinary decision-making, such as surgical planning or initiation of systemic therapy?

Dr Shersher: As mentioned previously, collaboration between health care providers in a multidisciplinary team is paramount today to treat lung cancer.  This team includes thoracic surgeons, medical oncologists, radiation oncologists, pathologists, diagnostic radiologists, and interventional pulmonologists. Ultimately, the decision to treat, and what order to treat in, is at the discretion of the multidisciplinary team and discussed extensively at a tumor board. Any delays in any part of the patient journey between these providers will delay initiation of treatment. The normal 10- to 14-day wait for molecular profiling of tumors is a challenging delay. Without reflexive testing, this delay can be significantly greater.

Although the median reduction in turnaround time was modest, the statistical significance was strong—how should oncologists interpret the clinical significance of this improvement in real-world practice?

Dr Shersher: I see this study as a guidance for other programs who may be struggling with long turnaround times. Despite a modest improvement in our turnaround time, there was still statistical significance. I personally hoped to see a more impressive difference in reduction in turnaround time. Perhaps this speaks more to the excellent quality and timeliness of our multidisciplinary program at Cooper MD Anderson in ordering these molecular tests without waiting for tumor board discussion prior to implementation of our reflex pathway. For other programs that may not have the same standards, perhaps they may see an even more impressive median reduction in NGS and PDL-1 turnaround if they implement a reflex testing paradigm at their institution.

Dr Edmonston: The next step for trying to shorten the TAT from procedure to biomarker result will be to shorten the time in the molecular lab, which can be achieved by selecting testing platforms with shorter turnaround times. Reducing the time to morphologic diagnosis by testing specimen types like cytology cell suspensions directly after rapid on-site evaluation could be considered as well.

What barriers might other institutions face when implementing reflex biomarker testing protocols, and what lessons from your experience could help oncology teams streamline adoption across different practice settings?

Dr Edmonston: The reflex biomarker testing approach works best if molecular testing can be performed at the institution where the patient is treated. The pathologist needs to have enough clinical information to determine whether the primary is likely to be clinical stage 1b and up, which may not be obvious in some specimens—especially cytology cases. Access to the electronic health record and the possibility to communicate with the treating clinician is therefore essential. The clinical team has to agree on the biomarker panel used in the reflex protocol, in our case a smaller (50 gene) NGS panel optimized for lung cancer. Another challenge is reimbursement, as the charges might fall under procedural billing codes or diagnosis-related groups (DRGs).