Opening her discussion on a patient case of recurrent endometrial cancer, Ritu Salani, MD, MBA, highlights the evolving role of molecular testing in this setting.
Case 1:A 64-Year-Old Woman With Recurrence of Endometrial Cancer
Patient History, Lifestyle and Clinical workup
Initial Diagnosis and Treatment
Presentation at Recurrence
Diagnosis of Recurrence
Treatment for Recurrence
Diagnosis of Recurrence
Ritu Salani, MD, MBA: Hello, my name is Ritu Salani. I’m a gynecologic oncologist and division director at UCLA in Los Angeles, California.
Today we’re going to review a case of recurrent endometrial cancer. The case starts in August 2021 with a 64-year-old postmenopausal woman who initially presented for abnormal uterine bleeding, which has been ongoing for the past 4 months.
The patient’s history is significant for noting menopause at age 55 years. She’s a widow with no children and lives alone. She has a past medical history significant for arthritis and obesity, [and she has] a BMI of 40. She has well-controlled hypertension, is on medication, and has [an ECOG] performance status of 1. After evaluation, an endometrial biopsy is performed and reveals an endometrioid adenocarcinoma. She undergoes surgery and is found to have a stage IA, grade 1 endometrial cancer. Immunohistochemistry staining is done and she’s noted to have mismatch repair deficiency as well as ER [estrogen receptor]-positive status.
The patient does well until July 2022 when she presents to your office noting chronic persistent pelvic pain over the past 4 weeks. Examination is unremarkable. Results of a chest, abdomen, and pelvic CT scan reveal metastatic disease involving the right external iliac lymph node. So at this time, we have to determine treatment for recurrence, and she receives carboplatin and paclitaxel for 6 cycles every 3 weeks and she tolerates this well. At the conclusion of her 6 cycles, [she has] a complete response.
She presents for a routine follow-up. In February 2023, she continues to have some symptoms, and a repeat CT scan is performed. On the scan, you notice an enhancing mass in the right super renal space, multiple bilateral pulmonary nodules, and enlargement of an internal iliac lymph node in addition to the previous one that had been observed. An FNA, or fine needle aspirate, of a super renal mass is performed and confirms metastatic endometrioid adenocarcinoma. You counsel the patient on systemic therapy options and she repeatedly expresses recurrent concerns about the [adverse] effects of treatment. After your review, you decide to initiate dostarlimab and she’s noted to have a partial response on CT scan 4 months after the initiation of therapy.
I’m just thinking of initial impressions of this case. It’s important to know that this is a typical case of endometrial cancer. One important note is that although this patient was diagnosed at an early stage, recurrence—although unlikely—can still happen, and it’s important to continue to monitor these patients with symptoms and examination, and then additional imaging as warranted.
Endometrial cancer’s landscape is changing rapidly, and molecular testing is becoming a key component for all patients with endometrial cancer. We recommend biomarker testing or molecular testing for all patients. One of the simple things to do is immunohistochemistry for mismatch repair testing, which can often be done at individual institution. This is looking for the presence of mismatch repair proteins to be intact or deficient and can help inform treatment.
Immunohistochemistry for mismatch repair proteins can be done at the time of diagnosis. It can be done on the biopsy or the hysterectomy specimen, but really it should be done at the initial diagnosis. One of the key components for this is that it can also help us understand which patients may have a genetic mutation that warrants further testing or germline testing. This would be [testing] for Lynch syndrome.
Additional testing may be warranted, and as we’re becoming more sophisticated in understanding molecular testing, it’s important to also test for other molecular markers. This can include ER expression, which may inform treatment down the road; p53 mutation or wild-type expression, which also can be informative and prognostic; as well as HER2 testing in certain cases. This is typically reserved for serous or carcinoma sarcomas, where this can be commonly seen and can also help inform treatment. If a patient has standard endometrioid endometrial histology, those molecular markers have been tested. Additional testing at the time of progression or recurrent disease may also be helpful. This can include things such as tumor mutational burden status, MSI [microsatellite instability] status, which does overlap with mismatch repair testing, but they’re not completely inclusive, and then rarer things such as NTRK fusions or other abnormalities that may also help determine treatment for these patients.
Standardly, we would do immunohistochemistry testing for mismatch repair deficiency at the time of diagnosis. But as our understanding of the molecular landscape of endometrial cancer from TCGA [The Cancer Genome Atlas] data is evolving, we need to be mindful that this is going to change. The upcoming FIGO [International Federation of Gynecology and Obstetrics] staging is changing and it’s going to incorporate p53 mutations or wild type as part of the staging landscape. So this will be important to have at the beginning. We’re also understanding additional information about POLE, and this might also be informative to have at the time of diagnosis to understand which patients require further follow-up, or which patients could potentially be deescalated from therapy. Now there will be clinical trials that help us understand this further. However, [these are] really exciting data that I think will move the molecular landscape into the time of initial diagnosis.
Transcript edited for clarity.