Nov. 12, 2024
In this article, Gretchen E. Glaser, M.D., a gynecologic oncologist at Mayo Clinic in Minnesota, discusses isolated tumor cells, a group of tiny malignant cells about 0.2 mm in diameter or less that can arise in the sentinel lymph nodes of patients with endometrial cancer. Dr. Glaser was the corresponding author of a 2024 International Journal of Gynecologic Cancer (IJGC) article on the prognostic value of sentinel lymph node isolated tumor cells (SLN-ITCs).
Does the presence of SLN-ITCs trigger additional treatment after surgery?
At this time, no prospective data exist to help gynecologic oncologists determine whether they should recommend adjuvant therapy to patients with otherwise low-risk endometrial cancer and SLN-ITCs.
Due to the lack of data on SLN-ITC and patient prognosis, medical centers vary in their uses of adjuvant therapy for patients with low-risk endometrial cancer and SLN-ITCs. Some medical centers give adjuvant therapy to any patient with SLN-ITCs, while others perform only observation in these patients.
How is endometrial cancer with SLN-ITCs in the lymph nodes staged?
SLN-ITCs are not currently part of the International Federation of Obstetrics and Gynecology (FIGO) endometrial cancer staging, either for 2009 or 2023. These guidelines are published in Obstetrics & Gynecology.
The American Joint Committee on Cancer, which has its own staging system for gynecologic cancers, has developed a new category for SLN-ITCs. These guidelines were published in 2017 in CA: A Cancer Journal for Clinicians.
Why did you conduct the study published in IJGC?
We initiated this study because there is no consensus in gynecologic oncology on how to manage SLN-ITCs. In addition, we wanted to conduct a multicenter study of SLN-ITCs, as previous studies of these cells had involved only a small number of participants due to the rarity of SLN-ITCs in patients with low-risk endometrial cancer.
What were your study's conclusions related to the presence of SLN-ITCs and patients' prognoses? Are patients with SLN-ITCs likely to die of their disease?
In this study, we determined that the presence of SLN-ITCs, FIGO grade 2 and lymphovascular space invasion plus no adjuvant therapy were independent risk factors for poorer recurrence-free survival for patients with low-risk endometrial cancer compared with patients who were node negative for SLN-ITCs with similar risk profiles. The five-year recurrence-free survival rates were 89.5% for patients with SLN-ITCs and 91.1% for patients with negative nodes.
Patients with SLN-ITCs also had worse nonvaginal recurrence-free survival than did patients with negative nodes. Nonvaginal recurrence-free survival estimates at five years were 88.2% for patients with SLN-ITCs and 91.9% for patients with negative nodes.
While patients with SLN-ITCs had poorer recurrence-free survival, their overall survival was similar to that of patients negative for SLN-ITCs.
How was this study conducted?
This retrospective study involved 15 medical centers that identified patients with SLN-ITCs between 2013 and 2019. The investigators compared these patients with others who were negative for SLN-ITCs. The cohort totaled 494 patients, 42 of whom had SLN-ITCs and 452 who did not. All these patients' endometrial cancers were classified as low-risk, and none of these patients had adjuvant therapy.
What did you observe during this study?
We observed recurrences in 21 (4.3%) of patients, including five with SLN-ITCs and 16 whose nodes were negative for SLN-ITCs. The recurrence was vaginal for one patient with SLN-ITCs and five with negative nodes. Recurrence was nonvaginal for four patients who had SLN-ITCs and 11 who had negative nodes.
The median follow-up for patients who did not experience recurrence was 2.3 years. On univariate analysis, significant risk factors for recurrence included the presence of SLN-ITCs, lymphovascular space invasion and FIGO grade 2.
Is the precise location of the endometrial cancer recurrence significant?
Yes. Vaginal recurrence is more treatable than nonvaginal recurrence, such as in the lymph nodes, lungs, liver or peritoneum. With vaginal recurrence, radiation therapy can salvage the top of the vagina, while recurrence in other locations can require additional treatment and prompt a poorer prognosis.
Prior to this study, how has Mayo Clinic managed SLN-ITCs for patients with low-risk endometrial cancer?
In our practice, we've used the presence of SLN-ITCs as a risk factor considered with other uterine risk factors impacting each patient's endometrial cancer treatment. If the patient has other uterine risk factors, we consider giving the patient adjuvant therapy. Without those other risk factors, we watch patients with SLN-ITCs closely, including performing imaging.
We recognize that any adjuvant therapy has lifelong side effects, which we and our patients must balance with the risk of recurrence.
How has observation only of patients with SLN-ITC worked so far?
We are conducting a prospective study of this exact situation with the same consortium as that in the aforementioned article. We will follow patients with SLN-ITCs over the next several years and perform CT scans every six months.
Do you recommend a SLN biopsy for patients with endometrial cancer? If so, should they be referred somewhere?
Yes. I recommend an SLN biopsy. The National Comprehensive Cancer Network recommends a SLN biopsy for all patients diagnosed with endometrial cancer.
This procedure is not performed in the community, however. A patient will need a SLN biopsy to be performed by a gynecologic oncologist at a medical center such as Mayo Clinic.
At Mayo Clinic, we do many SLN biopsies every single week and have a tumor board that meets weekly to discuss each patient's care plan. If a hometown physician referred the patient, we communicate with that physician for updates on the patient's care and any follow-up needed at home, and to address any other questions.
For more information
Cucinella G, et al. Prognostic value of isolated tumor cells in SLNs in low risk endometrial cancer: results from an international multi-institutional study. International Journal of Gynecologic Cancer. 2024;34:179.
Berek JS, et al. FIGO staging of endometrial cancer: 2023. Obstetrics & Gynecology. 2023;162:383.
Amin MB, et al. The eighth edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA: A Cancer Journal for Clinicians. 2017;67:93.
Refer a patient to Mayo Clinic.