Revolutionizing Endometrial Cancer Diagnostics
Eye on Innovation
In the intricate landscape of women's health, endometrial cancer stands as a significant concern, impacting the lives of thousands of individuals each year. As the fourth most common cancer among women in the United States, its prevalence underscores the need for more developments in testing.
As advancements in endometrial cancer diagnostics emerge, consultants from Mayo Clinic's Department of Laboratory Medicine and Pathology (DLMP) lead the industry in recent discoveries. Sounak Gupta, M.B.B.S., Ph.D., vice chair of Oncology Practice for the Division of Laboratory Genetics and Genomics (LGG); Maryam Shahi, M.D., senior consultant for Anatomic Pathology; and Andrea Mariani, M.D., M.S., division chair of Gynecologic Surgery, shed light on molecular profiling, the collaborative efforts that led to these innovations, and the groundbreaking impact on patient care.
The origin of this transformative journey harks back to the Cancer Genome Atlas project (TCGA), a multifaceted collaboration across institutions that laid the foundation for understanding multiple types of cancer beyond conventional histology. The project involved collecting and analyzing data from hundreds of tumor samples to identify genetic alterations and other molecular changes linked to cancer development and progression.
"The Cancer Genome Atlas project played a pivotal role in studying endometrial cancer through molecular profiling, allowing us to move beyond traditional histology," explained Dr. Gupta. "Incorporating molecular signatures, such as DNA mutations, has revolutionized the way we classify endometrial cancer and predict patient outcomes.”
The integration of these innovations into pathology reports became a cornerstone in diagnosing endometrial tumors. Mayo Clinic's approach involved emphasizing the integration of traditional histopathologic and molecular information. Molecular profiling of these tumors allows for a more sophisticated prognostication, enabling healthcare professionals to make informed decisions about treatment approaches. "Molecular signatures are becoming integral to pathology reports, offering a more detailed view of the tumor," said Dr. Gupta. “This holistic approach ensures a comprehensive understanding of tumors, marking a significant leap in patient care.”
At Mayo Clinic, molecular and anatomical pathologists, genetic counselors, and surgical and medical oncologists worked together to develop a meaningful and cost-effective test called the MayoComplete Endometrial Carcinoma Panel (Mayo ID: MCECP). Dr. Shahi, a key stakeholder in this collective effort, highlights the test's potential to offer crucial information for patient diagnoses. The comprehensive insights derived from the test results aid in understanding the tumor's behavior, assessing associated risks, and exploring personalized intervention strategies.
“This platform marks the initial phase of our efforts as we aim to propel the advancement of future testing,” Dr. Shahi shared. “In contrast to other institutions where molecular results and pathology reports exist separately, at Mayo Clinic, our collaborative effort among stakeholders has led to a comprehensive and unified report. This strength lies in our understanding of the significance of each molecular variation. As pathologists, we amalgamate this information to furnish the most meaningful insights for both patients and clinicians to act upon.”
To determine treatment options, pathologists consider the individual histopathologic characteristics of tumors. Some patients may not require aggressive treatments, as indicated by retrospective data revealing favorable outcomes for similar cases. Despite a tumor's alarming histologic appearance, molecular data may suggest a less intensive treatment approach in some cases. Conversely, seemingly low-grade tumors might possess a propensity for rapid progression, prompting clinicians to opt for aggressive treatments like chemotherapy or radiotherapy. The integrated information within pathology reports guides clinicians to recommend the optimal treatment or intervention based on a patient’s unique molecular profile.
While the data supporting molecular profiling has been accumulating in literature, the challenge lies in widespread adoption. Organizations such as the World Health Organization (WHO) and the National Comprehensive Cancer Network (NCCN) have provided recommendations to integrate these molecular classifications.
"Recommendations from WHO and NCCN endorse the adoption of molecular classifications, and Mayo Clinic has taken the lead in incorporating these advancements into our daily practice for patients treated at our facilities," Dr. Gupta affirmed.
Some examples featured in the new molecular guidelines include the identification of POLE alterations and microsatellite instability-high (MSI-H) status. Specific genomic categories, such as microsatellite instability, can guide the use of targeted therapies like immunotherapy. Retrospective analysis indicates that these subgroups may respond to therapy differently and could require escalation or de-escalation of therapy in contrast to past guidelines.
Dr. Andrea Mariani is actively involved in the NCCN’s Guidelines Panel for Uterine Neoplasms, which lays the groundwork for incorporating these tests into clinical practice through clinical trials. “The NCCN strongly recommends we implement molecular analysis, but we’re not quite ready to move this into clinical practice. We will need prospective clinical trials,” said Dr. Mariani. “We are still gathering information, as the transitional phase between research and clinical practice is not always a straightforward step.”
As endometrial cancer-specific molecular testing is implemented, challenges are expected. Mayo Clinic's approach includes offering a variety of testing options, from large gene panels to more focused tests, allowing providers to choose the optimum test based on each patient’s unique needs. In addition, LGG is exploring liquid biopsies as a potential avenue for predicting tumor recurrence.
One challenge that may arise during the integration process involves the need for funding. “There may be issues with insurance coverage for these tests,” explained Dr. Mariani. “However, because there is a significant movement to incorporate these tests into clinical practice, coverage is expected to improve in the next one or two years.”
Prospective clinical trials are essential to confirm the effectiveness of specific treatments for distinct groups. While retrospective data underscores the prognostic value of these tests, their validation in clinical practice hinges on prospective trials. Extensive utilization of these tests is imperative to gathering essential knowledge for smooth integration into clinical practice.
As challenges are navigated, Mayo Clinic Laboratories (MCL) remains at the forefront of this innovative discovery to shape the future of endometrial cancer diagnostics. Mayo Clinic’s leadership in adopting molecular classifications reinforces the institution’s commitment to ensuring patients receive the most effective and cost-conscious care.
Recognizing the powerful role genes can play in diagnosing illness and guiding treatment, the Division of Laboratory Genetics and Genomics at Mayo Clinic spearheaded a testing expansion, implementing and upgrading more than 60 advanced sequencing and biochemical assays in 2023 and planning for even more this year.
Endometrial cancer affects thousands annually and ranks as the fourth most common cancer among women in the United States. At the forefront of innovative discoveries in endometrial cancer diagnostics are Mayo Clinic's Department of Laboratory Medicine and Pathology consultants. Sounak Gupta, M.B.B.S., Ph.D., vice chair of Oncology Practice for the Division of Laboratory Genetics and Genomics; Maryam Shahi, M.D., senior consultant for Anatomic Pathology; and Andrea Mariani, M.D., M.S., division chair of Gynecologic Surgery, explore the critical significance of molecular profiling and collaborative efforts driving these innovations, highlighting Mayo Clinic’s revolutionary influence on patient care.
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