With the advent of next-generation sequencing (NGS) technologies just over a decade ago, genomic information became available not only in labs, but also in clinical practice. Today, genomic testing is starting to play an important role in cancer patient care. Knowing the genetic makeup of a tumor can help oncologists determine the best therapeutic options for a patient, making genomic testing a growing part of precision medicine.
Medical Lead, CCC Munich LMU
“Comprehensive genomic profiling or molecular testing is now an integral part of modern oncology. We use these tests to better understand a given disease, and, in the ideal world, to target treatments based on these results,” Benedikt Westphalen, MD, medical oncologist and molecular biologist, chair of the European Society for Medical Oncology’s (ESMO) Precision oncology Working Group and head of the Precision Oncology Comprehensive Cancer Center at the University of Munich, told Inside Precision Medicine.
As genomic testing slowly becomes standard-of-care and healthcare professionals enhance their genomic literacy, the relationship between ordering physicians and genomic testing entities comes into focus.
“There are various ways [in which] a treating physician can get genomic test results,” Westphalen explained. “There is in-house testing, meaning the hospital’s department of pathology runs the tests and the physician receives the test results. There’s also testing within commercial entities where physicians get the reports back, very lengthy, with a lot of additional information.”
Clinical practice gaps mean patients miss out
Although genomic profiling of tumors is advancing precision oncology, it is not helping all the patients it could. For example, a 2022 study published in JCO Precision Oncology looked at data from advanced non-small cell lung cancer (aNSCLC) patients and studied which of the newly diagnosed patients could have, but did not, benefit from a personalized treatment.
The study found that for every 1,000 patients, 497 (almost 50%) did not receive precision oncology options because of issues with biomarker tests. Among the remaining 503 patients who did receive biomarker test results, 147 did not receive targeted treatments. The results showed that about 64% of eligible patients with aNSCLC were not benefiting from personalized treatments, although they could be.
The authors concluded that “many patients do not receive the most effective personalized treatments because of challenges associated with integrating predictive biomarker testing into clinical care. Patients are lost at various steps along the precision oncology pathway because of operational inefficiencies, limited understanding of biomarker strategies, inappropriate testing result usage, and access barriers.”
It is likely, write the authors, that these clinical practice gaps are reflected in other cancer types as well. But what causes this detrimental gap between genomic testing results and the steps physicians may or may not take toward personalized treatments for their patients?
Chief Medical Officer, Guardant Health
Craig Eagle, MD, chief medical officer at Guardant Health, told Inside Precision Medicine: “Today, genomic results are primarily reported as lists of genetic mutations, alterations, or biomarkers that have been identified within a patient’s tumor. These results are typically presented in a standard report format, often requiring physicians to interpret complex genetic data, identify actionable mutations, and correlate them with potential therapeutic options … The information is often highly technical and can be overwhelming for physicians, particularly in fast-paced clinical settings, making it difficult to effectively integrate these findings into personalized treatment decisions.”
“Physicians have a ton of work to do,” Westphalen added. “So when they get these test results back, they have to be accessible for them in their daily clinical practice. They need to get an immediate idea of whether the test was successful, if it is informative, and if it supports the treatment options or management. Right now, if physicians have to sift through 40 to 60 pages, the report’s most relevant information could be lost.”
Hence, although the data found in genomic test reports is highly valuable and relevant to oncologists and their patients, the way it is often presented can result in confusion. In a worst-case scenario, a patient might miss out on a life-changing personalized treatment because important information gets “lost in translation.”
Senior Director, QIAGEN
Adding to this, Huw Ricketts, PhD, senior director of CLIA business development at QIAGEN, told Inside Precision Medicine: “The challenge that we see is that from different test providers, physicians will get different genomic reports containing different information, or the information is presented differently. This can be confusing and physicians may miss information or may not find the right information in the report.
“Another challenge is that there’s a lack of standardization among test providers in the interpretation of the data before it goes onto the report. Different tests can have different interpretation algorithms and result in different answers. This leads to different information being put onto the reports and physicians might not know what to do with the data if there are no clear guidelines regarding the therapeutic options or possible clinical trials that might be useful for the patient.”
What should a genomic test report look like?
To address these challenges and improve and harmonize genomic test reporting for patients and their ordering physicians, the ESMO Precision Oncology Working Group, together with Joris van de Haar, MD, PhD, of the department of molecular oncology and immunology at the Netherlands Cancer Institute, published new recommendations on clinical reporting of genomic test results for solid cancers to create an example of how a genomic test report should look so that physicians can make informed decisions.
“ESMO advocates for a shift towards reports that are more clinically actionable, more concise, and better aligned with treatment decision-making,” said Eagle. “I fully agree with this perspective. Genomic reports should not only present genetic findings but also provide clearer, more direct guidance on how those findings translate into treatment options.”
Ideally, a physician receiving a genomic report should immediately be able to extract the most important information by looking at the first page. Moreover, the report should contain a mixture of text, tables, and other graphical solutions to display complex information more comprehensively for patient readers and their ordering physicians, write the authors.
“The ideal report should immediately show who was tested, what was tested—blood and/or tissue—what type of testing was done, was it DNA, RNA, and the quality of the tests,” Westphalen explained. “The quality of the testing is important because it directly informs the clinician whether everything they were looking for is captured in this report. If, for example, the RNA sequencing did not go well, some very important information on highly relevant clinical targets might be lost.
“After the report has defined what was found and whether it was pathogenic or not, the very last part should show if the results are therapeutically and clinically relevant or not. So, at a glance, the physician and the patient can see this was successful and [be] able to measure what they’re looking for. … With what is shown, every clinician, and also an informed patient, can work very well towards the next steps.”
The big question: To include therapies and clinical trials data or not?
One area of heated discussion is the question of whether to include therapeutic and clinical trial options within the genomic test report. Westphalen explained that the results often come from a tumor or blood sample and that therapeutic or clinical trial options are only based on the tumor’s molecular profile without taking a patient’s situation into account.
“The worst thing that can happen is that the patient comes with a very comprehensive report listing a lot of therapeutic options, the physician is discussing the results, there are ten potential treatment options, and the doctor says no to all of them,” said Westphalen. “As a patient, you could get the feeling that your doctor is not providing you the therapeutic options that 70 pages have just offered you.”
Ricketts takes a different stand: “My personal view is if I was a patient, I’d want all the options presented to me so I could discuss them with my doctor. [At QIAGEN] we try to be as agnostic as possible. We try to be agnostic to the technology and the assay that is used to develop the report … but we’re also agnostic from a therapy perspective. It is not our place to tell a physician what they should or should not be offering. All we’re doing is pulling on the guidelines and saying these are the options for the patient. It’s up to the physician to have that discussion with the patient.”
“Additionally, actionable insights must be placed in the context of the patient’s clinical history and broader therapeutic landscape, incorporating options like clinical trials, targeted therapies, and novel treatments that are emerging in the field,” added Eagle. “Simplifying this complex data and providing actionable recommendations will ultimately enable physicians to make faster and more accurate precision treatment decisions, improving patient outcomes.”
Implementing ESMO’s recommendations across borders
In the future, the authors of ESMO’s recent recommendations on the clinical reporting of genomic test results hope that test providers use the recommendations as guidelines to improve their reporting and help physicians make informed decisions for their patients.
Westphalen told Inside Precision Medicine that he does not know if ESMO’s recommendations will be used on a large scale or across borders. However, he does believe that many people who build precision oncology programs or set up new molecular pathology departments will use the recommendations to “inform optimal practice.”
“One important point is that this type of genomic testing and reporting is not confined to ivory tower university medicine and highly qualified centers. Comprehensive genomic profiling is, in many malignancies, a very important component of standard of care patient management. So, to empower the greater oncology community, putting such recommendations out and also putting names out of whom to contact, in the end, will be important for scaling up these approaches.”
From an industry perspective, Ricketts believes that most genomic testing companies share the same goal, underlining the importance of standardization.
“I like to think that most companies are aiming for the same thing, which is making sure that more patients can get the right treatment at the right time,” he said. “I think as more precision medicines come up, there will be more and more information that needs to go into these reports. So there’s going to be more information on there—more drugs, more clinical trials, more options for the patients. I see that as a good thing, as long as all that data can be presented in a clear fashion to physicians and the data is clinically actionable.”
Eagle explained that as genomic testing becomes increasingly important to precision medicine, especially precision oncology, communication and collaboration between genomic testing companies and physicians will also evolve.
“Ultimately, communication will become more personalized and action-oriented, ensuring that the most scientifically up-to-date genomic insights are seamlessly incorporated into the patient’s treatment journey to maximize outcomes. By working together with physicians, we can help foster a more collaborative, efficient, and patient-centric approach in providing leading-edge cancer care,” Eagle concluded.
Read more:
- Seed, L.M. Horizon Scanning in Cancer Genomics: How Advances in Genomic Medicine Will Change Cancer Care Over the Next Decade. Curr Genet Med Rep (2021), doi.org/10.1007/s40142-021-00200-7
- Sadik, H., Pritchard, D., et al. Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer. JCO Precision Oncology (2022) doi.org/10.1200/PO.22.00246
- Van de Haar, J. et al. ESMO Recommendations on clinical reporting of genomic test results for solid cancers. Annals of Oncology (2024) 10.1016/j.annonc.2024.06.018
Larissa Warneck-Silvestrin is a freelance science journalist based in Berlin, Germany. She has a BSc in biology from Friedrich-Schiller University in Jena, Germany, and an MSc in science communication from the University of Kent in Canterbury, U.K. Larissa has written in English and German for several media outlets, including Labiotech, Deutsche Welle, and Inside Precision Medicine. She specializes in biotechnology, health, medicine, innovation, and biology.
