Advancing Precision: The Vital Role of Biomarker Testing in Endometrial Cancer

Endometrial cancer, the most prevalent gynecologic malignancy in high-income countries, is undergoing a profound clinical transformation. While traditional management has long relied on histopathologic categories, the rapid integration of precision medicine has shifted focus toward identifying specific molecular drivers to guide individualized therapy. Biomarker testing—encompassing mismatch repair (MMR) status and p53 expression—is now essential for refining prognostic risk and selecting targeted treatments. These advancements allow clinicians to distinguish between tumors requiring aggressive intervention and those suitable for treatment deescalation, ultimately minimizing toxicity while improving patient survival.

In a Community Case ForumTM event held in Denver, Colorado, John K. Chan, MD, director of gynecologic oncology and a specialist in the surgical and medical treatment of ovarian and other complex pelvic cancers at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, California, moderated a discussion about biomarker testing and treatment decisions in patients with endometrial cancer.

This is part 2 of a 2-part series.

Register today to join a Case-Based Roundtable near you.

CASE SUMMARY

A 64-year-old, postmenopausal woman presented with abnormal uterine bleeding for 4 months. She reports that menopause occurred at 55 years of age. She is a widow, has no children, and lives alone.

Past medical history

• G1P0
• Arthritis
• Obesity (BMI=40)
• Hypertension well controlled with daily ACE inhibitor
• ECOG performance status 1

DISCUSSION QUESTIONS

• When do you order biomarker testing, and how are you applying results?
• Should every postmenopausal patient with endometrial cancer undergo molecular testing?
• What do you discuss with your patients about biomarker testing, before initiating and when you have results?

John K. Chan, MD: In advanced stage disease, do you jump on Tempus right away, even before they recur?

William Lee, MD: I send liquid. You come in with metastatic disease, you get a liquid from me, and then we use Guardant360.

Chan: Do you use liquid in place, or do you do it in addition? You can’t do [immunohistochemistry; IHC] from liquid though. So, you’re sending tumor as well for the IHC?

Lee: I do them both, because I can get liquid back faster.

Chan: Have you guys adopted liquid?

Jeffrey James, DO: I get it because we have to draw blood. Tempus uses the patients as their base match normal, so I get it, but I don’t know that I’ve gathered any data that’s been helpful from it.

Chan: You find it to be noisy, rather than helpful? Or is it helpful?

Benjamin Scheier, MD: I think the discordance is more around false negatives. I think that the sensitivity is poor. How much faith do you put in it, I think is the challenge. Her cancer seems different.

Chan: This patient ended up going through surgery, and after surgery, she had stage 1, grade 1 uterine cancer. She was watched. [Deficient mismatch repair; dMMR], ER-positive. Nine months later, from her stage 1 cancer, she’s got relapse. She gets [carboplatin and paclitaxel] without [immunotherapy; IO].

Scheier: Honestly, that’s the challenge here, that you have to give a somewhat unrealistic case to make [pembrolizumab (Keytruda)/lenvatinib (Lenvima)] seem obvious.

Chan: Let’s play both games. Case 2a, she didn’t get it. Case 2b, she gets it. How do you assess prognostic risk; dMMR, better or worse than [proficient mismatch repair; pMMR]?

Robin Lacour, MD: dMMR is probably better.

Chan: Let’s say without [IO]. Do you think they recur more? You had a dMMR stage 1 vs a pMMR stage 1, do you think there’s more likelihood of recurrence with the dMMR or the pMMR?

James: I think they stay diseased for longer with dMMR  and that the disease still recurs at a similar rate.

Chan: You just feel like they do better, just because they respond better to IO, but I don’t know if from the nature aspect if there’s a difference. I think the jury’sout on that.

So, 7-month counseling, she gets [carboplatin and paclitaxel] with IO. And then she repeats. Lung mass 7 months later. This disease-free interval is about 7 months, and she biopsies, and it’s positive. Following initial, which factors influence your systemic chemotherapy selection? Let’s start with 2a, she didn’t get IO. How would you decide on treatment?

Lacour: I think you have a couple of options. Do chemo with IO, or, if she’s dMMR, [microsatellite instability], you could do [pembrolizumab] alone.

Chan: Which of these matters to you guys more? Does this time to relapse, 7 months, matter? Do you do that in breast and lung [cancer]? Look at disease-free intervals after chemo? Does that change your management?

Scheier: I think in small cell lung cancer, perhaps there are situations where you consider platinum.

Chan: And what about efficacy?

Lacour: If the patient already had [carboplatin and paclitaxel] and it’s only been 7 months, there’s a change that they still have some kind of residual adverse effects, or maybe they still have borderline neutropenia or thrombocytopenia. You have to take all of those things into account.

Chan: Toxicity matters a lot. Efficacy, does that matter? You got 7 months. No matter what you throw at them, they all respond about the same. Or do you think that [lenvatinib] adds better to just single-agent chemo? Because at 7 months, it’s unlikely they will go back on platinum-based chemotherapy.

Lacour: For us, it’s just an extrapolation from ovarian cancer. We have no data in endometrial cancer saying that this platinum-free interval is even in existence.

James: I think most of us look at metastatic, especially recurrent, metastatic endometrial cancers. How can I sequence this patient to give them the best quality and quantity as possible? Because I know I’m not going to win this, and that’s unfortunately where we are.

Chan: That’s why we keep talking about sequencing, right? We’re all basically saying, let me figure out what the journey is. What sequence can I give to get them that longest journey with less toxicity, with possibly better progression-free survival [PFS], and hopefully overall survival [OS]? Each incremental benefit we get in PFS hopefully will add to OS.

Register today to join a Case-Based Roundtable near you.

DISCLOSURES: Chan previously reported consulting fees from AstraZeneca, Daiichi Sankyo, Eisai, Ethicon, GlaxoSmithKline, Genmab, Immunogen, Karyopharm, Merck, Mersana, Moon Surgical, Myriad, Pfizer, Roche and Seagen; honoraria from AstraZeneca, Eisai, Ethicon, Genmab, GlaxoSmithKline, Immunogen, Merck, Myriad and Seagen; support for travel to attend meetings from AstraZeneca, Eisai, Ethicon, Genmab, GlaxoSmithKline, Immunogen, Merck, Myriad, Seagen and Pfizer; and participation on advisory board for AstraZeneca, GlaxoSmithKline and Myriad.