Patient Case 2: dMMR Recurrent Endometrial Carcinoma


Robert L. Coleman, MD, opens discussion on a second patient case and highlights critical aspects of mismatch repair deficient (dMMR) recurrent endometrial carcinoma.


Robert L. Coleman, MD, FACOG, FACS: Great discussion, as I said. So we’re going to now dig into a patient with an MMR deficient tumor. So [it is an] older patient; she’s 79 years old. She presents with kind of a multifocal pelvic recurrence of her endometrial cancer. And her history is [that in] 2016, she had a grade 2, stage 1B endometrioid cancer. It was thought to be ER [estrogen receptor] positive. And at that time she had total laparoscopic hysterectomy, a bilateral salpingo-oophorectomy, and she had a pelvic…lymph node dissection and was treated adjuvantly at that point with vaginal brachytherapy. So she does well for 6 years and then ultimately comes back with a vaginal cuff recurrence measuring over 3 cm, and it‘s biopsy-confirmed positive. So as part of that workup, she ends up getting a PET/CT [positron emission tomography/computed tomography], and it basically shows that she’s got an implant also anterior to the bladder, and she’s got some other kind of sub-centimeter pelvic nodules, and then another small nodule that’s a rectum abdominus mass, and then a FDG [F-fluorodeoxyglucose] avid lung lesion. And so she ends up going, I’m not sure why, but ends up going through a bronchoscopy to confirm that she’s actually got a recurrence of her disease in the lung. And is found again to have a dMMR [mismatch repair deficient] tumor that was ER positive and HER2 [human epidermal growth factor receptor 2] nonamplified, or HER2 negative. Now, one thing I do kind of mention, and with these patients, we see them down here a lot because we have a lot of fungus in the soil. We do have a lot of patients who have lung lesions that are FDG avid, which oftentimes turn out to be noncancerous. So it’s one of those things, it’s just hard in the totality of the situation. You kind of have to deal with it. But in this patient who’s already got disease that’s intraperitoneal, I think this was kind of a low risk for a false positive. Let me start with you, Krish. At this point, what would you recommend for her care? So she’s, again, just treated with radiation.

Krishnansu S. Tewari, MD: She had vaginal cuff brachytherapy 6 years ago. At this point, evaluating her [ECOG] performance status and everything, I’ve talked to her about combination chemotherapy. With platinum and Taxol [paclitaxel]. If she had a very poor performance status, I may even try to give her hormonal therapy given the lesion is ER [estrogen receptor] positive.

Robert L. Coleman, MD, FACOG, FACS: Sowhen do you try that? She’s 79.

Krishnansu S. Tewari, MD: I’ve done it in patients that have isolated pulmonary metastases that are not resectable, who aren’t very symptomatic and don’t want to do chemotherapy, and I’ve had some good results doing that for some people. But multifocal recurrences in different parts of the body [is where] I’ve not had very good luck with hormonal therapy.

Robert L. Coleman, MD, FACOG, FACS: Dr Birrer?

Michael J. Birrer, MD, PhD: Well, I really agree with that. She had a 6-year interval. So you look at that estrogen receptor and say, “Hmm, maybe this thing is more indolent than I think.” So I think that’s reasonable. I would love to be able to give her [a] single-agent immune checkpoint [inhibitor therapy], but we’re not quite there yet. So then, chemotherapy. The only other point I would make on this case, because I always like to, other than harass my gynecology/oncology colleagues, I like to harass the radiation oncologist. She had brachytherapy and still recurred at the distal end of the vagina. So thank you very much.

Robert L. Coleman, MD, FACOG, FACS: Right.

Krishnansu S. Tewari, MD: That’s a problem with writing the case. So, that’s a problem, the patient shouldn’t have received radiation to begin with, and then when she relapses, she should have multifocal disease, so that radiation’s not an option.

Robert L. Coleman, MD, FACOG, FACS: There you go. Exactly. Well, one thing we mentioned in the first case, and I’ll just remind people that we had a patient that was actually pMMR [mismatch repair proficient] in her initial assessment. This patient wasn’t tested [for] pMMR in the initial [work-up], and then when she recurred, basically in the same place, it was kind of a distal urethra anterior vaginal wall recurrence. It was biopsied again as an endometrial cancer and was retested, and actually it was dMMR [mismatch repair deficient] at that point in time. So we see about 10% of the time that these tumors can convert. It’s not very often, as I mentioned, but just something to keep in mind. This patient was tested with her recurrence and was found to have that. I agree with you, Michael, I think that our hope is that we’ll have a confirmatory trial to say that we can maybe replace chemotherapy at this step. But we’re not there yet. Just as you mentioned, she ended up getting paclitaxel with carboplatin and, again, gets 6 cycles of treatment. And she’s NED [no evidence of disease]. So again, kind of a pretty remarkable outcome. But she gets a rapid recurrence. So 4 months later PET/CT [positron emission tomography/computer tomography] [shows she has] lesions in the lung and chest cavity, and a biopsy is consistent…with recurrent disease. So in this particular situation, she’s got a relatively short interval. Kimberly, you mentioned this in your discussion that maybe with a long interval, we might be comfortable giving reinduction with therapy. I think here you probably would agree that going back into chemotherapy is not probably a great option, but she does have a biomarker for which we have an approved drug. I’d be curious, in your setting, Kimberly, how would your practice approach a patient like this with dMMR tumor?

Kimberly Halla, MSN, FNP-C: Actually, it’s going to be very patient-driven as well right. Because now she’s 79 years old, she’s treatment in, she’s got a 4-month recurrence. What is her expectation at this point, right? Are we looking for longevity? Are we looking for quality vs quantity? What does she want to do? And really let that patient drive that discussion as well.

Robert L. Coleman, MD, FACOG, FACS: Krish, your thoughts on a treatment option here?

Krishnansu S. Tewari, MD: That’s unfortunate that she had a complete response but progressed in the lower lung 4 months later. I would talk to her about checkpoint [inhibitors], it’s an appropriate strategy for her. You talk to her about [adverse] effects and everything. Again, this is another patient you can also consider hormonal therapy for. And as far as checkpoint [inhibitors go], as you point out on this slide, we do have options now.

Robert L. Coleman, MD, FACOG, FACS: Absolutely.

Transcript edited for clarity.

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