Leiomyosarcoma (LMS) is a rare gynecologic malignancy, but it contributes to a significant proportion of uterine cancer deaths. Most LMS cases are uterine-confined, early-stage disease, and while surgery is the mainstay of treatment, recurrence rates continue to be high. “Even with adjuvant chemotherapy, approximately 50% of patients will have their LMS recur,” says Anthony B. Costales, MD. “These recurrences are largely incurable and fatal.”

In general, most clinical trials investigating treatment modalities for LMS—including radiation therapy and adjuvant chemotherapy—have failed to demonstrate a survival benefit compared with observation. “Given the rarity of LMS, data are needed to establish if adjuvant chemotherapy can improve oncologic outcomes,” Dr. Costales says. “Such data could facilitate our discussions with patients on what can be expected with this type of treatment and guide our decision making on the optimal course of action.”

Identifying Important Trends

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A study published in the Journal of Gynecologic Oncology, Dr. Costales and colleagues assessed the survival impact of adjuvant chemotherapy in women with LMS. Using data from the 2008–2014 National Cancer Database, the analysis involved 1,030 women with early-stage disease. “We wanted to see if adjuvant therapy improved oncologic outcomes—specifically, overall survival,” explains Dr. Costales. “We also wanted to determine if we could identify a certain population of women with specific uterine factors that could benefit from adjuvant chemotherapy.” He adds that these data may help identify trends in adjuvant treatment in the absence of prospective randomized data.

Most patients in the study received observation (53.1%) or chemotherapy alone (33.0%) while far fewer received radiation alone (7.7%) or chemoradiation (6.2%). Patients were more likely to be treated with observation if their tumor size was smaller than 5 cm and less likely to be observed if lymphovascular space invasion (LVSI) was present. Patients were more likely to receive chemotherapy if they were younger and if they had LVSI.

Assessing Prognostic Indicators

When investigators looked at factors relating to mortality, they found that older patients, those with tumors larger than 5 cm, and those with LVSI had worse survival rates. The strongest predictor of mortality was the presence of LVSI. The study authors noted that their analysis is among the first to show that LVSI in women with LMS is associated with a poorer prognosis. The median overall survival for the entire cohort was 62 months.

“Our study showed that no type of adjuvant therapy—including adjuvant chemotherapy—in early stage, uterine confined LMS improved overall survival when compared with observation,” Dr. Costales says (Figure). “In a subgroup analysis assessing the impact of clinicopathologic factors, none of the patient subgroups had an improved mortality rate when compared with observation.” The 3-year overall survival rate for observation, chemotherapy, and radiation, was 73.7%, 71.3%, and 68.2%, respectively.

Reexamining the Approach

“Our study adds to what has been seen in other studies of women with early stage, uterine confined LMS,” says Dr. Costales. “The data support that observation should be considered standard of care rather than adjuvant chemotherapy. At most, adjuvant chemotherapy should be discussed with patients, but clinicians should not advocate for it since we lack data showing that this strategy improves survival. As healthcare providers, we are responsible for presenting data to patients to help them make the best possible decision on treatment. The unfortunate reality is, regardless of whether they choose chemotherapy or observation, their survival chances are the same.”

Dr. Costales notes that translational studies are needed to better identify which patients with LMS may benefit from adjuvant chemotherapy. “Future research should seek to determine if mutational signatures or subtypes may identify patients who can benefit from adjuvant chemotherapy,” he says. “It would also be beneficial to test novel therapies that may target identified mutations. Importantly, since LMS is rare, clinical trials investigating women with the disease will inevitably be small. It may be difficult to accept, but observation may be the best option for women with early stage LMS until more data emerge.”

References

Costales AB, Radeva M, Ricci S. Characterizing the efficacy and trends of adjuvant therapy versus observation in women with early stage (uterine confined) leiomyosarcoma: a National Cancer Database study. J Gynecol Oncol. 2020;31(3):e21. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189070/.

Ricci S, Giuntoli RL 2nd, Eisenhauer E, et al. Does adjuvant chemotherapy improve survival for women with early-stage uterine leiomyosarcoma? Gynecol Oncol. 2013;131:629-633.

Seagle BL, Sobecki-Rausch J, Strohl AE, Shilpi A, Grace A, Shahabi S. Prognosis and treatment of uterine leiomyosarcoma: a National Cancer Database study. Gynecol Oncol. 2017;145:61-70.