Precision Medicine Testing in Oncology: Benefits of and Barriers to Adoption

J Clin Pathways. 2023;9(5):15-17.

Founded in 2016, the Clinical Pathways Forum is a com­munity of pathways professionals—now totaling over 12 institutions from across the US—who are utilizing clini­cal pathways in their practices and institutions to improve cancer care. Forum leader Mishellene McKinney, MHA, RN, OCN, organizes quarterly conference calls with Forum members to facilitate discussion of shared experi­ences and lessons learned regarding pathway use as clini­cal pathways become more prevalent and evolve to meet the needs of value-based health care systems and reim­bursement models.

The mission of the Clinical Pathways Forum is to facilitate a knowledge exchange for overcoming the challenges of developing, implementing, and measuring clinical pathways to demonstrate the value of standardizing clinical care. The main activity of the Forum is to schedule time quarterly for confer­ence calls to share experiences and lessons learned using clinical pathways.

The Forum publishes highlights from each of the Forum conference calls that occur throughout the year in the Journal of Clinical Pathways (JCP). This second installment for 2023 sum­marizes the speakers and discussion from the May 2023 call. Health care professionals from across the continuum of care are encouraged to join in these collaborative discussions. Forum con­tact information can be found in the online version of this article.

On May 23, 2023, Suzzette Arnal, PhD, Senior Director of Precision Medicine at The US Oncology Network, addressed the Clinical Pathways Forum about precision medicine and how The US Oncology Network (US Oncology) has worked to in­crease precision medicine testing across their organization.

The evidence is clear: Patients with actionable mutations who receive targeted therapy have improved survival. However, operationalizing precision medicine evidence into practice has proven to be challenging. The MYLUNG study found that only 46% of 3500 patients with stage IV non–small cell lung cancer (NSCLC) in The US Oncology Network received appropriate biomarker testing from 2018 to 2020.¹ These re­sults are consistent with similar studies done in other practices across the US. US Oncology has identified precision medicine as an ideal opportunity for decision support tools to provide just-in-time knowledge about the best treatment for a patient.

Precision medicine testing, including genetics and genom­ics, is used in oncology to identify high-risk patients and pre­vent cancer, diagnose cancer earlier, choose the best treatment options, and evaluate the efficacy of a treatment. Once a cancer has been identified, it becomes important to choose the correct treatment options and then finally evaluate how those treat­ments are working.

There are multiple known therapeutic targets driven by mo­lecular alterations that target specific molecular alterations and there are over 47 000 tests on the market. For a busy commu­nity oncologist who isn’t specialized in any one cancer type but is seeing 30-40 patients a day with breast cancer, lung cancer, colorectal cancer, and myeloproliferative disorders, it can be challenging to stay up to date with changing guidelines. It’s critical to have support tools that can direct oncologists toward the right test and the right treatment.

Dr Arnal explained that instead of ordering multiple tests, comprehensive profiling can help simplify and speed up the time to treatment. For example, when looking at metastatic NSCLC and the actionable biomarkers according to guidelines, there are several to be considered. These include PCR (polymerase chain reaction, which detects genetic material), FISH (fluorescence in situ hybridization, a test that looks for gene changes in cells) and IHC (immunohistochemistry screening, which looks to see if certain proteins are absent in the tumor sample).

The advantage of comprehensive profiling, or next-genera­tion sequencing (NGS), is that it creates the opportunity to look at all these biomarkers at the same time, from the same sample. Often there is only a scant tissue sample the size of a grain of sand or rice. Rather than trying to perform multiple tests from different slices of tissue, it’s possible to do one NGS test and get the same information all at once. The only thing that can’t be assessed are protein-based biomarkers like PD-L1, which needs to be ordered as a separate test. Using NGS reduces the over­ all cost compared with doing sequential testing. Cost and the time to therapy are reduced because it eliminates the need to do sequential testing, wait for those results, and then test again.

The term “biomarker” is used broadly. Biomarkers can be found in blood, urine, or tissue, and they are representative of an underlying condition or disease. When the term “biomarker testing” is used in precision medicine, it can refer to genomic testing, mutation testing, molecular testing, or genomic profil­ing. Dr Arnal stated that she prefers to use the term “compre­hensive genomic profiling” when talking about looking at bio­markers that are representative of a tumor sample. These can be somatic mutations that are definitive, or they can show what’s happening in the cancer tissue itself. This is in contrast with germline mutations, which are inherited and require different testing techniques to assess for.

Biomarkers can be diagnostic, prognostic, or predictive. Dr Arnal emphasized that precision medicine is primarily fo­cused on predictive biomarkers, but prognostic biomarkers also present useful information in the community oncology space. Most of the biomarkers fall into two different catego­ries: driver mutations, which are linked to therapeutic targets, and immunotherapy markers like PD-L that suggest how the tumor is interacting with the immune system.

Biomarker testing is an important part of the patient jour­ney, yet it doesn’t always happen at the right time. In 2022, the American Society of Clinical Oncology recommended or­dering multigene panel testing when there is more than one genomic biomarker linked to an FDA-approved therapy. It can take several weeks to get a patient scheduled to see the oncolo­gist. Only then is the biomarker test ordered, and it can take close to three weeks to see the results of the test. To shorten the time to the correct treatment, it’s important to know at the time of diagnosis that a biomarker test needs to be ordered.

US Oncology identified an opportunity to set up collabor­ative ordering agreements with pathology to reflexively order testing. This intervention has helped reduce the time to treat­ment to get the results. Dr Arnal said, “I think of our tissue as glitter spread across the country—we have tissue that’s every­where. It’s challenging to set up this type of relationship with pathology everywhere in our network. But when we can do it, it really improves the ability to get those results in quickly.”

Testing rates in The US Oncology Network have increased from the time of the MYLUNG study to around 55%-60%. In speaking with US Oncology physicians and in reviewing the literature, it’s clear there are many barriers to adoption of pre­cision medicine testing. Some of the key barriers to adoption include suboptimal tissue procurement and operational inef­ficiencies; fragmented insurance coverage; inadequate reim­bursement and lack of specificity in coding; lack of specificity in selection and interpretation; lack of decision support; and long turnaround times for test results.

Dr Arnal emphasized that among these barriers to broader use of precision medicine, one of the biggest barriers is inad­equate reimbursement and lack of specificity in coding. The main driver behind the lack of payment is fragmented insur­ance coverage. Dr Arnal stated that patients with Medicare have the most access to comprehensive genomic profiling, but many private payers are still hesitant to pay for panels with over 50 genes because they think it’s experimental.

Payers are an important stakeholder because they often dic­tate who gets access to the testing. In some states, Medicaid doesn’t cover comprehensive genomic profiling, which Dr Arnal feels is contributing to inequities in cancer care. Some private payers, such as UnitedHealthcare, have historically covered a limited number of tests, and only recently changed their guidance to cover some of the large panels included in FDA-approved tests and indications.

Coding is another key barrier to precision medicine test­ing. Most genetic and rare diseases do not have correspond­ing ICD-10 codes, which creates a barrier to wider adoption. There are only three general codes used for billing, with a wide variation for reimbursement between the three codes, ranging from $600 to $2900. There are also Proprietary Labo­ratory Analyses (PLA) codes, which manufacturers can apply for from the American Medical Association. For example, Guardant and FoundationOne have PLA codes that can be used for reimbursement as a way of more specifically identify­ing their tests. The Centers for Medicare & Medicaid Services has created a set of guidelines through the MolDX (Molecular Diagnostics Tests) coverage determination that specifies pa­rameters to establish coverage and reimbursement for testing. For private payers, that process is less clear, but typically they are looking for analytical and clinical validity.

In response to physician requests, the US Oncology team started revolutionizing their electronic medical records (EMR) to handle molecular results. At US Oncology, like many orga­nizations, the results were essentially being shoehorned into tables that were meant to house things like complete blood count data. US Oncology created a section of the EMR to house molecular results with structured data, instead of having to look through the documents section, the pathology section, or the results section for PDF reports.

US Oncology uses a clinical pathways tool called Clear Value Plus that guides the provider to enter diagnosis, stage, line of therapy, biomarker status, and other parameters. At the time of initial pathway entry, a provider may not know if the patient has an ALK fusion or BRCA mutation, or whether a test is recommended. To provide that needed front-end sup­port, a genomic ordering module was built. When a physician enters the patient’s diagnosis and the disease stage, a pop-up message, guided by the patient’s diagnosis and stage, provides NCCN testing recommendations. Only test options that have been vetted by the US Oncology team and are commercially available are presented. Additionally, US Oncology built bidi­rectional interfaces with the lab that load results immediately after they are obtained. Physicians don’t need wait for a fax or go to an external portal to find them.

The field of precision medicine is growing rapidly. There are over 700 companies participating in oncology clinical trials, and there are currently over 800 ongoing late-stage clinical tri­als, about half of which include genomic biomarkers. Dr Arnal predicted we will see increased testing and the identification of even more biomarkers that will drive therapy selection. While the May 23 discussion primarily focused on therapy selection, precision medicine has applications throughout the entire con­tinuum of care, from identifying risk screening to diagnostic testing and identifying prognostic markers. As the clinical ev­idence develops and matures, Dr Arnal feels we will start to see more adoption if significant impact to the patient and their overall survival is demonstrated.

Dr Arnal predicted we will start to see more use of minimal residual disease in solid tumors, similar to what’s been seen in the hematology space. She added that it’s exciting to see the developments in artificial intelligence and digital pathology, citing new products that can find a RET fusion from just look­ing at an image. She concluded the presentation by saying, “I think where we would all love to see this go is combining im­aging and molecular data altogether. So, histopathology, ra­diology, molecular data, and giving the most comprehensive care plan that we can for our patients. I feel like we are on the cusp again of something big.”

Additional Clinical Pathways Forum Events

On August 15, 2023, we heard from Steven Edge, MD, FACS, FASCO, Vice President of Health Care Outcomes and Policy and Professor of Oncology at Roswell Park Comprehensive Cancer Institute in Buffalo, New York. In this session, Dr Edge spoke about the use of prospective pathways at Roswell Park. Stay tuned for highlights of this discussion in a future issue of the Journal of Clinical Pathways.