Not All Stage I and II Endometrial Cancers Are Alike

Sudha Amarnath, MD

For patients with endometrial cancer, stratification into risk subgroups is essential to alleviate the risk of overtreatment or undertreatment. A recent retrospective study by Mariam AlHilli, MD, found that patients in International Federation of Gynecology and Obstetrics (FIGO) stage I high- intermediate risk subgroups with fewer than 2 risk factors (FIGO grade 2 or 3, lympho-vascular space invasion [LVSI], or stage IB) had a greater than 95% cause-specific survival at 3-year follow-up and subgroups with 2 or more risk factors had poorer outcomes. Patients in FIGO stage II subgroups had poorer outcomes, regardless of histology. No endometrial cancer–related deaths after 3 years were reported in patients with FIGO stage IA nonendometrioid endometrial cancer without myometrial invasion.¹

“The data [show] that a large proportion of patients with early-stage disease are very well served with minimal treatment, such as observation or vaginal brachytherapy, after surgery,” said Sudha Amarnath, MD, study coauthor and a radiation oncologist at Cleveland Clinic’s Taussig Cancer Institute in Ohio. “But for patients with specific risk factors, we need to consider escalating therapy to a greater degree.”

Assessing Risk Factors

One of the most common gynecologic cancers, endometrial cancer is often identified early when patients present with postmenopausal bleeding. Although outcomes are quite good in these cases, there is a need to better stratify patients beyond general low-risk, intermediate-risk, and high-risk categories to determine who will need more treatment such as external beam radiation or chemotherapy. Notably, for those with certain risk factors, such as grade 3 disease, deep myometrial invasion, or LVSI—even in early-stage disease—there is a high likelihood of distant recurrence. It is crucial to be able to identify these cases and potentially alter the course of the disease.

“Although recurrence risk has been analyzed in several clinical trials, there is a lot of variability and heterogeneity in patients’ care as well as trial inclusion criteria, so it’s difficult to ascertain the best treatment for patients in each subgroup,” Amarnath said.

To that end, the study investigators identified 4156 patients with FIGO stage I high-risk and stage II endometrioid endometrial cancer and stage I and II nonendometrioid endometrial cancer who received surgery at Cleveland Clinic or Mayo Clinic in Rochester, Minnesota, between 1999 and 2016 (Figure).¹

Figure. Patient Characteristics

The 3-year risk-free survival and cause-specific survival were identified in 16 subgroups, based on each patient’s risk factors. The study results demonstrated that observation or vaginal brachytherapy may only be sufficient treatment for stage I high-intermediate risk disease with fewer than 2 risk factors among grade 3, LVSI, or stage IB or stage IA nonendometrioid disease without myometrial invasion.

Next Steps

As investigators gather more genomic and molecular data, the hope is that they will be able to identify markers that might indicate a good or poor prognosis.

“There is a lot of enthusiasm around innovating and developing personalized therapies that are more effective for patients,” Amarnath said. In the meantime, she encourages clinicians to ensure patients experiencing symptoms such as abnormal bleeding, difficult or painful urination, or pain during intercourse are screened. “Postmenopausal bleeding is never normal, and patients should be screened promptly to ensure the best outcome.”