Improved Survival in Metastatic Uterine Cancer With Hysterectomy Plus Chemo

— Data extend surgery's advantage from locally advanced to distant metastases

MedicalToday
A close up of a woman in a hospital lowering her waistband to reveal a medical dressing over a hysterectomy scar.

Total abdominal hysterectomy (TAH), in addition to chemotherapy, significantly improved overall survival (OS) in patients with newly diagnosed uterine cancer and distant metastases, a large retrospective analysis showed.

The survival hazard decreased by more than 40% with the addition of TAH, and a propensity score-matched analysis showed almost a 9-month gain in median OS. Landmark analyses for 1- and 2-year OS also yielded significant advantages for patients who underwent TAH.

TAH plus chemotherapy improved survival for all subgroups except patients with leiomyosarcoma and those with brain metastases, reported Yuefeng Wang, MD, PhD, of West Cancer Center and Research Institute in Memphis, and co-authors.

"Palliative TAH was included in the 2021 NCCN [National Comprehensive Cancer Network] guideline for uterine cancer with distant-organ metastasis," the authors wrote in the study online in . "However, the role of TAH as a definitive treatment approach has not been established. To our knowledge, this analysis represents the largest reported cohort of patients with metastatic uterine cancer treated by local therapies."

"Randomized clinical trials to evaluate the effect of TAH on distant metastatic uterine cancer appear to be warranted," the team concluded.

The study provided intriguing data for a difficult diagnosis that is associated with an overall survival of about a year, said Claire Hoppenot, MD, of Baylor College of Medicine and Dan L. Duncan Comprehensive Cancer Center in Houston, who was not involved with the research.

"Chemotherapy is the first-line treatment. These findings suggest that there may be a role for hysterectomy, either at diagnosis, if feasible, or after neoadjuvant chemotherapy," she told via email.

"These large database studies are always limited by the data collected; however they do a good job in their statistical analysis to address the concern that only patients who have a good response to chemotherapy would be taken for surgery," Hoppenot continued. "The addition of radiation in select patients may also be beneficial, although there may be a reverse causality in that patients who live longer get more treatments, and I do not believe that this has been adjusted specifically for radiation. This data is certainly very intriguing and I would discuss the findings with patients in making treatment decisions."

Several studies have shown that TAH with maximal cytoreduction in addition to chemotherapy increases survival for patients with newly diagnosed uterine cancer and associated abdominal or pelvic metastases.

The role of TAH in uterine cancer with distant metastasis has yet to be established, Wang and co-authors noted. Evidence from studies of other cancer types has suggested a potential survival improvement with definitive local therapy in the setting of distant metastasis, including prostate, lung, and cervical cancers.

To address the impact of TAH in uterine cancer and distant metastasis, the researchers queried the for the years 2010 to 2014 to identify patients with newly diagnosed uterine cancer and metastasis to the brain, lung, liver, bone, or distant lymph nodes. All patients included in the analysis received chemotherapy, with or without TAH.

The analysis included 3,197 patients, and mean age was 62. The most common site of metastasis was the lung (1,544 patients), followed by liver (851), lymph nodes (497), bone (249), and brain (56). The authors found that 1,809 patients received chemotherapy alone and 1,388 received chemotherapy plus TAH. The cohort had a median follow-up of 13.4 months.

The results showed that the addition of TAH resulted in a survival hazard ratio of 0.57 by univariate analysis (95% CI 0.53-0.62) and 0.59 by multivariable analysis, as compared with chemotherapy alone. The propensity score-matched analysis yielded median OS values of 19.8 months with TAH and 11.0 months with chemotherapy alone, representing a 41% reduction in the survival hazard (95% CI 0.53-0.65).

Subgroup analysis showed that only patients with leiomyosarcoma (HR 0.72, 95% CI 0.51-1.02) and those with brain metastases (HR 0.47, 95% CI 0.07-3.16) did not derive significant benefit from TAH.

In the TAH group, 79% of patients received chemotherapy after surgery. That subgroup also had statistically significant improvement in media OS as compared with chemotherapy alone (18.8 vs 10.3 months).

In a separate analysis, the authors compared survival in 228 patients who received definitive pelvic radiotherapy and 143 who underwent TAH plus radiotherapy, in addition to chemotherapy. Both groups had significant reductions in the survival hazard versus chemotherapy alone (HR 0.60 and HR 0.34, respectively).

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined in 2007.

Disclosures

No funding support for the study was noted.

Wang reported no disclosures; co-authors reported financial relationships with AstraZeneca, EISAI, Precision Oncology, Bristol Myers Squibb, Caris Life Sciences, George Clinical Consulting, Compugen, Concerto Health, Immunocore, Amgen, OneOncology, and Novocure.

Primary Source

JAMA Network Open

Wang Y, et al "Comparison of chemotherapy vs chemotherapy plus total hysterectomy for women with uterine cancer with distant organ metastasis" JAMA Netw Open 2021; DOI: 10.1001/jamanetworkopen.2021.18603.