Published research has shown that women with ovarian cancer have among the highest rates of venous thromboembolisms (VTEs) of all patients with cancer. “An estimated 5% to 25% of patients with ovarian cancer will have a VTE within the first 2 years after their cancer diagnosis,” says Kristin S. Weeks, BS. “These patients will subsequently have higher morbidity and mortality. Importantly, VTEs have been identified as a leading secondary cause of death among patients with ovarian cancer.”
According to Weeks, many risk factors associated with ovarian cancer pathology and treatment may contribute to the elevated VTE risk. “Unfortunately, our understanding of risk factors is limited by sparse manuscripts and analyses over the last 3 decades that have mostly presented unadjusted odds ratios (ORs) or raw number comparisons,” she says. “It’s important to improve our understanding of risk factors so we can better screen for and prevent VTEs with appropriate anticoagulation, especially in our most high-risk patients.”
A Welcome Meta-Analysis
To address the current research gap, Weeks and colleagues conducted a meta-analysis of the most reported and discussed risk factors for VTE in patients with ovarian cancer to summarize and quantify the results of prior literature and clarify heterogeneity between the results in prior studies. The study was published in Obstetrics and Gynecology International. The investigators used PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature to identify observational studies. The meta-analysis included 20 cohort studies with 6,324 total patients with ovarian cancer, 769 of whom experienced a VTE. A random effects model was used to calculate the pooled ORs for VTE with advanced cancer stage, clear cell histology, serous histology, ascites at diagnosis, and complete cytoreduction. The I2 and Q tests were used to evaluate heterogeneity.
“The most important findings from our research were that the odds of VTE in patients with ovarian cancer were 2.7 times higher among those with cancer stage III/IV than those with stage I/II disease, 2.1 times higher among women with clear cell histology than those with nonclear cell histology, and 2.1 times higher among patients with ascites at diagnosis than those without ascites,” says Weeks (Figure). Conversely, serous histology (compared with nonserous histology) and complete cytoreduction (versus incomplete cytoreduction) were not associated with VTE, with corresponding ORs of 1.26 and 1.05, respectively.
According to Weeks, the most important clinical implication from the study is the correlation between high stage, clear cell histology, and ascites at diagnosis and VTE risk in patients with ovarian cancer. “When treating patients with ovarian cancer, suspicion for VTE could be raised when women with have high-stage disease, clear cell histology, or ascites at diagnosis,” she says.
Weeks says clinicians should include stage, clear cell histology, and ascites at diagnosis in clinical decision-making tools for VTE screening and preventative interventions in their efforts to manage women with ovarian cancer. “The most commonly used anticoagulation risk assessment tools are nonspecific for patients with ovarian cancer or do not include important variables like histology,” she notes. “Thus, more tools need to be developed. However, prior to developing these tools, robust multidisciplinary team efforts should consider the benefits and risks of interventions in the context of the risk factors identified in our study.”
Weeks says a prospective, multicenter, cohort study with a multivariable analysis is needed to assess the independent risk of VTE in women with ovarian cancer by treatment risk factors, tumor factors, and hospital care variables. “In addition, future studies are needed to assess risks and benefits of screening tools, anticoagulation tools, and the subsequent individualized interventions that are developed,” she adds. “As these tools emerge, I hope we will be able to improve outcomes in our patients with ovarian cancer.”
Weeks KS, Herbach E, McDonald M, Charlton M, Schweizer ML. Meta-analysis of VTE risk: ovarian cancer patients by stage, histology, cytoreduction, and ascites at diagnosis. Obstet Gynecol Int. 2020; 2020:2374716. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486642/.
Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Onc. 2007;25(34):5490-5505.
Shinn E. H., Lenihan D. J., Urbauer D. L., et al. Impact of cardiovascular comorbidity on ovarian cancer mortality. Cancer Epidemiol Biomarkers Prevention. 2013;22(11):2102–2109. doi: 10.1158/1055-9965.epi-13-0625.
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