“According to current estimates, approximately 9% of patients with uterine cancer have metastatic disease at the time of their initial presentation,” says Yuefeng Wang, MD, PhD. “In addition to systemic therapy, total abdominal hysterectomy (TAH) with maximal cytoreduction has been shown to increase survival for patients with abdominal or pelvic metastases. However, the role of TAH for uterine cancer with distant organ metastasis has not been established.”

Evidence is growing that definitive local therapies may increase survival for some types of metastatic cancers, says Matthew Ballo, MD, FACR. “Therefore, it’s compelling and critical to understand the role of using TAH as a definitive treatment approach for uterine cancer with distant organ metastasis,” he says. Of note, palliative TAH was included in the 2021 National Comprehensive Cancer Network guideline update for uterine cancer with distant organ metastases. However, the role of TAH as a definitive treatment approach for these patients has not been established.

Can Combo Therapy Improve Survival?

For a study published in JAMA Open Network, Dr. Wang, Dr. Ballo, and colleagues evaluated overall survival for uterine cancer patients with distant organ metastasis treated with chemotherapy alone versus chemotherapy plus TAH. Using the National Cancer Database (NCDB), the investigators identified patients with newly diagnosed uterine cancer with metastasis to the brain, lung, liver, bone, or distant lymph nodes. “All patients received chemotherapy with or without TAH,” Dr. Wang says. “Patients who received no treatments, definitive pelvic radiotherapy, or those missing baseline variables were excluded.”

From 2010-2014, the study team identified 3,197 patients meeting inclusion criteria. “Among these patients, 1,809 received chemotherapy alone and 1,388 received chemotherapy plus TAH,” says Dr. Wang. “At a median follow up of 13.4 months, TAH plus chemotherapy was associated with improved survival by both univariate (HR, 0.57) and multivariate analysis (HR, 0.59) when compared with chemotherapy alone (Figure). A propensity score-matched analysis demonstrated superior median survival (19.8 vs 11.0 months; HR, 0.59;) for TAH plus chemotherapy.”

A subgroup analysis was also performed by metastatic site, number of metastatic sites, and histology. “In the subgroup analysis, TAH plus chemotherapy had significantly improved survival over chemotherapy alone for all subgroups, except patients with leiomyosarcoma (HR, 0.72) or metastasis to the brain (HR, 0.47),” Dr. Wang notes.

Among surgical patients, 79% underwent TAH followed by chemotherapy, and these patients had significantly better survival than those receiving chemotherapy alone, with a median survival of 18.8 months versus 10.3 months, respectively. In the NCDB, the study team identified 228 patients who received definitive pelvic radiotherapy and 143 who underwent TAH and radiotherapy, in addition to chemotherapy. Both of these patient groups also had improved survival when compared with those receiving chemotherapy alone (HRs, 0.60 and 0.34, respectively).

Reasonable to Recommend Definitive TAH

Collectively, these findings support that definitive local therapy may benefit distant metastatic uterine cancer. “In the literature, there is very limited data about using TAH for uterine cancer with distant organ metastasis,” Dr. Ballo explains. “To our knowledge, this analysis represents the largest reported cohort of patients with metastatic uterine cancer treated by local therapies. Based on our findings, we think it’s reasonable to recommend definitive TAH for young patients who have good performance status and limited metastatic disease burden.”

Although data from the study showed that patients with newly diagnosed uterine cancer who have distant organ metastases and receive TAH plus chemotherapy live substantially longer than those receiving chemotherapy alone, more research is needed regarding the role of TAH in this patient population. “Our analysis was a retrospective, hypothesis-generating study,” says Dr. Wang. “Randomized clinical trials appear to be warranted to further evaluate the effect of TAH on distant metastatic uterine cancer.”