On November 6, 2026, OncoDaily, in partnership with Natera, hosted “Seismic Shift: Innovations in MRD Testing and Pathology,” a virtual webinar examining how advances in molecular residual disease (MRD) testing are changing cancer monitoring, pathology workflows, and clinical decision-making.
The session featured Dr. Joe Lennerz, Medical Director for Pathology Innovations at Natera, and was hosted by Dr. Sona Karamyan of OncoDaily.
The discussion explored the growing clinical role of circulating tumor DNA (ctDNA), the integration of molecular testing with digital pathology, and the practical challenges of bringing these technologies into routine oncology care. Particular attention was given to the interpretation of MRD results, treatment decisions guided by molecular findings, and access to testing across different healthcare systems.
Seismic Shift: Innovations in MRD Testing and Pathology
A Fourth Dimension in Cancer Monitoring
Opening the scientific presentation, Dr. Lennerz described MRD testing as a fourth dimension in oncology, complementing imaging, conventional clinicopathological assessment, and established serum biomarkers.
Traditional cancer monitoring relies heavily on imaging and pathological characteristics such as tumor type, grade, and stage. Although these remain essential, they have limitations in identifying microscopic disease and predicting an individual patient’s course.
Circulating tumor DNA testing introduces an additional approach by detecting tumor-derived genetic material in the bloodstream, potentially identifying residual disease before it becomes visible on conventional imaging.
Dr. Lennerz emphasized that this development is also changing the role of pathology. Rather than ending with the examination and reporting of a surgical specimen, pathology can now contribute to the development of personalized molecular assays used throughout a patient’s follow-up.
From Tumor Tissue to Personalized Molecular Surveillance
A central part of the presentation focused on Signatera, Natera’s tumor-informed MRD assay.
Dr. Lennerz explained how genomic information obtained from an individual tumor can be used to identify tumor-specific variants and construct a personalized assay for subsequent blood-based monitoring.
He distinguished this approach from comprehensive genomic profiling (CGP). While CGP primarily identifies actionable molecular alterations that may inform treatment selection, MRD testing addresses a different clinical question: whether cancer remains detectable after treatment and how its molecular burden changes over time.
To illustrate its clinical application, Dr. Lennerz presented the case of a 71-year-old patient with stage IIA colon cancer who underwent left hemicolectomy and was initially managed with observation.
Following initially negative ctDNA results, subsequent testing detected molecular evidence of disease. Additional imaging identified an 11-mm metastatic lesion, leading to treatment with stereotactic body radiotherapy (SBRT) and FOLFOX chemotherapy.
Following treatment, ctDNA levels returned to undetectable levels and remained negative during subsequent monitoring.
The case demonstrated how molecular surveillance can provide additional information alongside imaging and potentially influence further clinical evaluation and treatment.
Beyond ctDNA: Bringing Digital Pathology Into the Picture
Another major focus was the integration of MRD testing with computational pathology.
Dr. Lennerz discussed how digitized tissue slides contain information extending beyond conventional histological assessment. Computational approaches can examine morphological patterns, tumor architecture, and other tissue characteristics that may provide additional insight into tumor biology.
He presented work from Natera’s computational pathology team, including the development of models using a training dataset of approximately 45,000 colorectal cancer patients.
The presentation highlighted differences in the ability of computational models to predict molecular features from histological images. For example, microsatellite instability prediction showed substantial improvements as training datasets increased, whereas predicting specific alterations such as KRAS mutations remained more challenging.
Dr. Lennerz described a potential integrated model combining tissue-derived measures of tumor aggressiveness with dynamic ctDNA results.
In this framework, tissue analysis could provide a more static assessment of biological risk, while serial MRD testing could offer information about changes in molecular disease burden over time.
He emphasized that the added clinical value of combining these approaches remains an area of ongoing investigation.
When Molecular Results Challenge Conventional Imaging
During the discussion, Dr. Karamyan raised a question frequently encountered in clinical practice: how should oncologists interpret a positive ctDNA result when conventional imaging shows no evidence of disease?
The conversation addressed the clinical significance of low-level ctDNA positivity, the possibility of false-positive and false-negative findings, and the importance of distinguishing analytical performance from demonstrated clinical utility.
Dr. Lennerz referred to evidence from the IMvigor011 trial in muscle-invasive bladder cancer, discussing the use of ctDNA results to guide treatment decisions involving atezolizumab.
He highlighted the importance of prospective evidence in determining when molecular findings can support treatment initiation or the avoidance of unnecessary therapy.
For clinical settings where such evidence is not yet established, he described approaches including repeat molecular testing, additional imaging, and multidisciplinary reassessment.
The discussion also addressed Natera’s research into treatment decisions based on molecular results, with studies examining whether interventions triggered by ctDNA findings can improve outcomes across different tumor types.
The Challenge of Access: Bringing MRD Testing Beyond Major Cancer Centers
One of the session’s central discussions concerned the accessibility of advanced molecular testing.
Drawing on her clinical experience in Armenia, Dr. Karamyan highlighted the difficulties faced by healthcare professionals in settings where MRD testing requires international specimen shipment, access to appropriately stored tumor tissue, and substantial out-of-pocket expenses.
She raised the question of whether less frequent testing could offer a practical alternative for patients unable to undergo regular molecular surveillance.
Dr. Lennerz acknowledged that specimen procurement and coordination between pathology laboratories and oncology centers remain challenging even in the United States and Western Europe.
He emphasized the importance of strengthening communication among pathologists, oncologists, surgeons, and radiation oncologists to ensure appropriate tissue selection and efficient testing workflows.
The discussion also examined the financial sustainability of MRD testing and the need to generate evidence of clinical utility that can support reimbursement decisions.
Dr. Lennerz suggested that investigator-initiated studies, multinational research collaborations, and locally generated clinical evidence could help healthcare systems demonstrate the value of molecular testing and engage public or private payers.
Which Cancers Could Benefit Next?
The conversation also examined tumor types in which ctDNA-guided clinical decisions may become increasingly relevant.
Dr. Lennerz identified several areas of interest, including breast cancer, particularly triple-negative breast cancer, head and neck cancers, melanoma, cervical cancer, and gastrointestinal malignancies such as hepatocellular carcinoma, gastroesophageal cancer, and cholangiocarcinoma.
In breast cancer, the discussion focused on the possibility of using molecular monitoring to better inform treatment duration and potentially reduce unnecessary exposure to therapies associated with substantial toxicity.
However, Dr. Lennerz emphasized that the clinical utility of MRD testing varies according to tumor biology, disease characteristics, and the available evidence.
He also discussed the distinction between tumor-informed and tumor-naive assays, noting that access to appropriate tumor tissue is an important consideration when selecting a testing strategy.
The Missing Link: Pathology Workflows and Multidisciplinary Coordination
Questions from the audience brought additional attention to the practical aspects of implementing MRD testing.
Dr. Lennerz identified pre-analytical coordination as one of the most significant challenges, particularly when the appropriate tissue block must be identified and transferred between different healthcare institutions.
Incorrect specimen selection, insufficient tumor material, and communication gaps between clinical and pathology teams can interfere with efficient testing.
He emphasized that sophisticated molecular technologies must be supported by equally reliable clinical workflows.
The discussion also revisited the continuing importance of conventional pathology, including features such as lymphovascular invasion, perineural invasion, mitotic activity, and tumor microenvironment characteristics.
Although computational pathology may eventually identify additional biological patterns, Dr. Lennerz acknowledged that these emerging approaches still require further clinical validation.
Looking Ahead: A More Connected Approach to Cancer Care
As the webinar concluded, the discussion turned to the future integration of MRD testing into routine oncology practice.
Dr. Lennerz expressed optimism that molecular surveillance would become increasingly incorporated into clinical guidelines and monitoring strategies by 2030, while acknowledging that establishing comparable evidence across all solid tumors remains challenging.
The session reinforced the importance of viewing MRD testing not as a replacement for conventional pathology or imaging, but as an additional source of information that can support more individualized patient management.
In her closing remarks, Dr. Karamyan emphasized the importance of multidisciplinary collaboration and communication among oncologists, pathologists, radiologists, surgeons, and other specialists.
“Seismic Shift: Innovations in MRD Testing and Pathology” brought together the scientific developments and practical questions shaping the next phase of molecular cancer monitoring. From personalized ctDNA assays to computational pathology and equitable access, the webinar highlighted both the opportunities and the work still needed to translate these advances into everyday clinical practice.
The webinar was presented by OncoDaily in partnership with Natera on November 6, 2026.
On November 6, 2026, OncoDaily, in partnership with Natera, hosted “Seismic Shift: Innovations in MRD Testing and Pathology,” a virtual webinar examining how advances in molecular residual disease (MRD) testing are changing cancer monitoring, pathology workflows, and clinical decision-making.
The session featured Dr. Joe Lennerz, Medical Director for Pathology Innovations at Natera, and was hosted by Dr. Sona Karamyan of OncoDaily.
The discussion explored the growing clinical role of circulating tumor DNA (ctDNA), the integration of molecular testing with digital pathology, and the practical challenges of bringing these technologies into routine oncology care. Particular attention was given to the interpretation of MRD results, treatment decisions guided by molecular findings, and access to testing across different healthcare systems.
A Fourth Dimension in Cancer Monitoring
Opening the scientific presentation, Dr. Lennerz described MRD testing as a fourth dimension in oncology, complementing imaging, conventional clinicopathological assessment, and established serum biomarkers.
Traditional cancer monitoring relies heavily on imaging and pathological characteristics such as tumor type, grade, and stage. Although these remain essential, they have limitations in identifying microscopic disease and predicting an individual patient’s course.
Circulating tumor DNA testing introduces an additional approach by detecting tumor-derived genetic material in the bloodstream, potentially identifying residual disease before it becomes visible on conventional imaging.
Dr. Lennerz emphasized that this development is also changing the role of pathology. Rather than ending with the examination and reporting of a surgical specimen, pathology can now contribute to the development of personalized molecular assays used throughout a patient’s follow-up.
From Tumor Tissue to Personalized Molecular Surveillance
A central part of the presentation focused on Signatera, Natera’s tumor-informed MRD assay.
Dr. Lennerz explained how genomic information obtained from an individual tumor can be used to identify tumor-specific variants and construct a personalized assay for subsequent blood-based monitoring.
He distinguished this approach from comprehensive genomic profiling (CGP). While CGP primarily identifies actionable molecular alterations that may inform treatment selection, MRD testing addresses a different clinical question: whether cancer remains detectable after treatment and how its molecular burden changes over time.
To illustrate its clinical application, Dr. Lennerz presented the case of a 71-year-old patient with stage IIA colon cancer who underwent left hemicolectomy and was initially managed with observation.
Following initially negative ctDNA results, subsequent testing detected molecular evidence of disease. Additional imaging identified an 11-mm metastatic lesion, leading to treatment with stereotactic body radiotherapy (SBRT) and FOLFOX chemotherapy.
Following treatment, ctDNA levels returned to undetectable levels and remained negative during subsequent monitoring.
The case demonstrated how molecular surveillance can provide additional information alongside imaging and potentially influence further clinical evaluation and treatment.
Beyond ctDNA: Bringing Digital Pathology Into the Picture
Another major focus was the integration of MRD testing with computational pathology.
Dr. Lennerz discussed how digitized tissue slides contain information extending beyond conventional histological assessment. Computational approaches can examine morphological patterns, tumor architecture, and other tissue characteristics that may provide additional insight into tumor biology.
He presented work from Natera’s computational pathology team, including the development of models using a training dataset of approximately 45,000 colorectal cancer patients.
The presentation highlighted differences in the ability of computational models to predict molecular features from histological images. For example, microsatellite instability prediction showed substantial improvements as training datasets increased, whereas predicting specific alterations such as KRAS mutations remained more challenging.
Dr. Lennerz described a potential integrated model combining tissue-derived measures of tumor aggressiveness with dynamic ctDNA results.
In this framework, tissue analysis could provide a more static assessment of biological risk, while serial MRD testing could offer information about changes in molecular disease burden over time.
He emphasized that the added clinical value of combining these approaches remains an area of ongoing investigation.
When Molecular Results Challenge Conventional Imaging
During the discussion, Dr. Karamyan raised a question frequently encountered in clinical practice: how should oncologists interpret a positive ctDNA result when conventional imaging shows no evidence of disease?
The conversation addressed the clinical significance of low-level ctDNA positivity, the possibility of false-positive and false-negative findings, and the importance of distinguishing analytical performance from demonstrated clinical utility.
Dr. Lennerz referred to evidence from the IMvigor011 trial in muscle-invasive bladder cancer, discussing the use of ctDNA results to guide treatment decisions involving atezolizumab.
He highlighted the importance of prospective evidence in determining when molecular findings can support treatment initiation or the avoidance of unnecessary therapy.
For clinical settings where such evidence is not yet established, he described approaches including repeat molecular testing, additional imaging, and multidisciplinary reassessment.
The discussion also addressed Natera’s research into treatment decisions based on molecular results, with studies examining whether interventions triggered by ctDNA findings can improve outcomes across different tumor types.
The Challenge of Access: Bringing MRD Testing Beyond Major Cancer Centers
One of the session’s central discussions concerned the accessibility of advanced molecular testing.
Drawing on her clinical experience in Armenia, Dr. Karamyan highlighted the difficulties faced by healthcare professionals in settings where MRD testing requires international specimen shipment, access to appropriately stored tumor tissue, and substantial out-of-pocket expenses.
She raised the question of whether less frequent testing could offer a practical alternative for patients unable to undergo regular molecular surveillance.
Dr. Lennerz acknowledged that specimen procurement and coordination between pathology laboratories and oncology centers remain challenging even in the United States and Western Europe.
He emphasized the importance of strengthening communication among pathologists, oncologists, surgeons, and radiation oncologists to ensure appropriate tissue selection and efficient testing workflows.
The discussion also examined the financial sustainability of MRD testing and the need to generate evidence of clinical utility that can support reimbursement decisions.
Dr. Lennerz suggested that investigator-initiated studies, multinational research collaborations, and locally generated clinical evidence could help healthcare systems demonstrate the value of molecular testing and engage public or private payers.
Which Cancers Could Benefit Next?
The conversation also examined tumor types in which ctDNA-guided clinical decisions may become increasingly relevant.
Dr. Lennerz identified several areas of interest, including breast cancer, particularly triple-negative breast cancer, head and neck cancers, melanoma, cervical cancer, and gastrointestinal malignancies such as hepatocellular carcinoma, gastroesophageal cancer, and cholangiocarcinoma.
In breast cancer, the discussion focused on the possibility of using molecular monitoring to better inform treatment duration and potentially reduce unnecessary exposure to therapies associated with substantial toxicity.
However, Dr. Lennerz emphasized that the clinical utility of MRD testing varies according to tumor biology, disease characteristics, and the available evidence.
He also discussed the distinction between tumor-informed and tumor-naive assays, noting that access to appropriate tumor tissue is an important consideration when selecting a testing strategy.
The Missing Link: Pathology Workflows and Multidisciplinary Coordination
Questions from the audience brought additional attention to the practical aspects of implementing MRD testing.
Dr. Lennerz identified pre-analytical coordination as one of the most significant challenges, particularly when the appropriate tissue block must be identified and transferred between different healthcare institutions.
Incorrect specimen selection, insufficient tumor material, and communication gaps between clinical and pathology teams can interfere with efficient testing.
He emphasized that sophisticated molecular technologies must be supported by equally reliable clinical workflows.
The discussion also revisited the continuing importance of conventional pathology, including features such as lymphovascular invasion, perineural invasion, mitotic activity, and tumor microenvironment characteristics.
Although computational pathology may eventually identify additional biological patterns, Dr. Lennerz acknowledged that these emerging approaches still require further clinical validation.
Looking Ahead: A More Connected Approach to Cancer Care
As the webinar concluded, the discussion turned to the future integration of MRD testing into routine oncology practice.
Dr. Lennerz expressed optimism that molecular surveillance would become increasingly incorporated into clinical guidelines and monitoring strategies by 2030, while acknowledging that establishing comparable evidence across all solid tumors remains challenging.
The session reinforced the importance of viewing MRD testing not as a replacement for conventional pathology or imaging, but as an additional source of information that can support more individualized patient management.
In her closing remarks, Dr. Karamyan emphasized the importance of multidisciplinary collaboration and communication among oncologists, pathologists, radiologists, surgeons, and other specialists.
“Seismic Shift: Innovations in MRD Testing and Pathology” brought together the scientific developments and practical questions shaping the next phase of molecular cancer monitoring. From personalized ctDNA assays to computational pathology and equitable access, the webinar highlighted both the opportunities and the work still needed to translate these advances into everyday clinical practice.
The webinar was presented by OncoDaily in partnership with Natera on November 6, 2026.