Key Takeaways
- Biomarker testing leads to better patient outcomes in endometrial cancer since it enables targeted treatments by subtypes
- A review last year found that biomarker testing is more common among academic practices compared with community practices despite proven effectiveness of subtyping to determine treatment
- Community practices cite cost as a main barrier to testing and a desire for more prospective data to support treatment decisions based on subtype results
Biomarker classifications and immunotherapy have significantly improved patient outcomes for patients with endometrial cancer (EC), particularly in advanced and recurrent disease, but biomarker testing isn’t consistently executed among community oncology practices.1
A review published in Frontiers in Oncology earlier this year synthesizes how 4 molecular subtypes—patients with mutations in polymerase epsilon (POLE-mutant or POLEmut), mismatch repair–deficient (MMRd), and p53-abnormal (p53abn), and no specific molecular profile—each carry distinct biological behaviors, recurrence patterns, and treatment responses that now directly shape therapeutic decision-making.1
MMRd tumors show objective response rates of 40% to 50% to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors, making MMR status the gateway to some of the most effective therapies now available.1 The p53abn subtype, by contrast, overlaps heavily with high-grade histologies and carries the worst prognosis; NCCN guidelines prioritize platinum-based chemotherapy combined with antiangiogenic targeted therapy for these patients.1
At the other end of the spectrum, POLEmut patients exhibit near-100% recurrence-free survival in retrospective data, suggesting close follow-up for 5 years, versus aggressive adjuvant therapy.
“Chemotherapy-free” strategies are showing promise for select subtypes, particularly MMRd, and represent a potential path to reducing toxicity without sacrificing efficacy.
“Future research should focus on optimizing the molecular classification, overcoming immunotherapy resistance, and conducting real-world studies to further enhance treatment efficacy and achieve individualized therapy,” the authors wrote in their conclusion.1
Despite the progress, biomarker testing is not yet reaching all patients equally. A 2025 mixed-methods study by Wilson and colleagues, conducted across NRG Oncology–affiliated programs and published in Cancer, showed that while clinicians widely recognize the importance of molecular profiling, significant implementation gaps persist.2
Community-based practice clinicians did less biomarker classification than their academic counterparts, and only 24.2% of survey respondents said that POLE testing was moderately easy or very easy to obtain.
Qualitative interviews revealed that barriers to testing included cost, along with a desire for more prospective data to support treatment decisions based on subtype results.
The authors conclude that strategies to improve equitable access to biomarker classification are urgently needed.2
“Implementing molecular profiling can translate National Institutes of Health–supported research into direct patient benefit, improve care for patients with early-stage EC, and potentially reduce disparities in EC,” the authors wrote in their conclusion.2
In Practice Insight With Our Board
“Clinicians and payers need to understand that the most expensive drug in the world is the one that does not work. There is value to know in advance if a drug is more likely to work in a specific patient. The advantage of targeted therapy using biomarkers is that we now have a better idea if a drug works. Clinicians need to push that these tests are valuable. We need to demonstrate that biomarker patterns improve outcomes, and as the data are published and evolve, payers should embrace this testing. Like other tests we do routinely, these biomarker tests need to become standard of care.”
—Scott Soefje, PharmD, MBA,
Director of Pharmacy, Cancer Care Services,
and Associate Professor of Pharmacy at Mayo Clinic.
References
- Yan L, Ding X, Deng Y, et al. The molecular classification ushers in a new era for the treatment of advanced and recurrent endometrial cancer. Front Oncol. 2026;15:1761159. doi:10.3389/fonc.2025.1761159
- Wilson EM, Huang R, Jones KD, et al. Challenges in implementation of molecular classification in early stage endometrial cancer—an NRG Oncology cooperative group mixed-methods study. Cancer. 2025;131:e35596. doi:10.1002/cncr.35596
Key Takeaways
- Biomarker testing leads to better patient outcomes in endometrial cancer since it enables targeted treatments by subtypes
- A review last year found that biomarker testing is more common among academic practices compared with community practices despite proven effectiveness of subtyping to determine treatment
- Community practices cite cost as a main barrier to testing and a desire for more prospective data to support treatment decisions based on subtype results
Biomarker classifications and immunotherapy have significantly improved patient outcomes for patients with endometrial cancer (EC), particularly in advanced and recurrent disease, but biomarker testing isn’t consistently executed among community oncology practices.1
A review published in Frontiers in Oncology earlier this year synthesizes how 4 molecular subtypes—patients with mutations in polymerase epsilon (POLE-mutant or POLEmut), mismatch repair–deficient (MMRd), and p53-abnormal (p53abn), and no specific molecular profile—each carry distinct biological behaviors, recurrence patterns, and treatment responses that now directly shape therapeutic decision-making.1
MMRd tumors show objective response rates of 40% to 50% to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors, making MMR status the gateway to some of the most effective therapies now available.1 The p53abn subtype, by contrast, overlaps heavily with high-grade histologies and carries the worst prognosis; NCCN guidelines prioritize platinum-based chemotherapy combined with antiangiogenic targeted therapy for these patients.1
At the other end of the spectrum, POLEmut patients exhibit near-100% recurrence-free survival in retrospective data, suggesting close follow-up for 5 years, versus aggressive adjuvant therapy.
“Chemotherapy-free” strategies are showing promise for select subtypes, particularly MMRd, and represent a potential path to reducing toxicity without sacrificing efficacy.
“Future research should focus on optimizing the molecular classification, overcoming immunotherapy resistance, and conducting real-world studies to further enhance treatment efficacy and achieve individualized therapy,” the authors wrote in their conclusion.1
Despite the progress, biomarker testing is not yet reaching all patients equally. A 2025 mixed-methods study by Wilson and colleagues, conducted across NRG Oncology–affiliated programs and published in Cancer, showed that while clinicians widely recognize the importance of molecular profiling, significant implementation gaps persist.2
Community-based practice clinicians did less biomarker classification than their academic counterparts, and only 24.2% of survey respondents said that POLE testing was moderately easy or very easy to obtain.
Qualitative interviews revealed that barriers to testing included cost, along with a desire for more prospective data to support treatment decisions based on subtype results.
The authors conclude that strategies to improve equitable access to biomarker classification are urgently needed.2
“Implementing molecular profiling can translate National Institutes of Health–supported research into direct patient benefit, improve care for patients with early-stage EC, and potentially reduce disparities in EC,” the authors wrote in their conclusion.2
In Practice Insight With Our Board
“Clinicians and payers need to understand that the most expensive drug in the world is the one that does not work. There is value to know in advance if a drug is more likely to work in a specific patient. The advantage of targeted therapy using biomarkers is that we now have a better idea if a drug works. Clinicians need to push that these tests are valuable. We need to demonstrate that biomarker patterns improve outcomes, and as the data are published and evolve, payers should embrace this testing. Like other tests we do routinely, these biomarker tests need to become standard of care.”
—Scott Soefje, PharmD, MBA,
Director of Pharmacy, Cancer Care Services,
and Associate Professor of Pharmacy at Mayo Clinic.
References
- Yan L, Ding X, Deng Y, et al. The molecular classification ushers in a new era for the treatment of advanced and recurrent endometrial cancer. Front Oncol. 2026;15:1761159. doi:10.3389/fonc.2025.1761159
- Wilson EM, Huang R, Jones KD, et al. Challenges in implementation of molecular classification in early stage endometrial cancer—an NRG Oncology cooperative group mixed-methods study. Cancer. 2025;131:e35596. doi:10.1002/cncr.35596
