Venous Thromboembolism: An Unrecognized Crisis in Gynecologic Oncology

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The past decade has witnessed a growing emphasis on creating and proving the existence of high value in health care through implementation of enhanced recovery pathways, bundled interventions, and other standardized protocols that have improved outcomes and lowered costs.1,2 Despite these improvements, treatment gaps persist for patients with ovarian cancer, among them, achieving further reductions in morbidity associated with both cancer and its treatments. Venous thromboembolism continues to be a common and serious source of morbidity among women with ovarian cancer.
The rate of clinically evident venous thromboembolism at the time of ovarian cancer diagnosis is approximately 3%. Among women undergoing primary surgery for ovarian cancer, nearly 17% will develop venous thromboembolism within 30 days without prophylaxis.3,4 Extended administration of chemical prophylaxis may reduce the 30-day risk by 78%, but these benefits may not be maintained over a longer follow-up period, suggesting that a longer course of prophylaxis may be beneficial.5 Thus, the duration and efficacy of prophylaxis after surgery are subjects of ongoing study. However, the burden of thromboembolic events in the neoadjuvant setting has thus far evaded scrutiny. In this issue of Obstetrics & Gynecology, Greco et al6 (see page 979) report that 27% of patients who received neoadjuvant chemotherapy suffered a venous thromboembolism, a rate higher than what has been observed postoperatively without prophylaxis. This is an important finding, especially considering that the rate is likely to be an underestimation without subclinical venous thromboembolism assessment. Furthermore, recognizing that the threshold to administer neoadjuvant chemotherapy varies between surgeons and institutions, and that the same patient and tumor factors that drive the decision for neoadjuvant chemotherapy are also risk factors for venous thromboembolism, the venous thromboembolism rate may be higher for groups with a lower neoadjuvant chemotherapy rate (26% received neoadjuvant chemotherapy in the Greco et al series). Additional investigation is needed in larger, preferably national datasets. If a high venous thromboembolism rate is confirmed elsewhere, adaptive approaches to mitigate venous thromboembolism risk in this cohort should be pursued, with the goal of creating practice guidelines and quality measures.
Perioperative and extended-duration venous thromboembolism prophylaxis after pelvic surgery is a National Hospital Inpatient Quality Measure endorsed by The Joint Commission, National Quality Forum, and the Centers for Medicare & Medicaid Services.7–9 However, these guidelines were created based on risk scores developed in open general surgery, and refinement in the setting of gynecologic oncology surgery has been suggested.10 Guidelines for outpatient venous thromboembolism prophylaxis are vague for many cancer diagnoses.9 Although two randomized trials of prophylactic dose low-molecular-weight heparin for venous thromboembolism prevention during chemotherapy in solid tumors were positive,11,12 the low baseline rates of venous thromboembolism in these cohorts have led to debate regarding risk–benefit ratio and cost-effectiveness. Prophylaxis with nadroparin or semuloparin was shown to result in a 50–64% reduction in venous thromboembolism risk to a rate of 2% and 1.2%, but women with ovarian cancer comprised only 12% of enrolled patients in both trials.11,12 The low baseline rate of venous thromboembolism likely reflects the risk heterogeneity of the included cancers, limiting generalizability of these results to patients with ovarian cancer, but it provides initial suggestion of benefit. These trials have generated discussion of the merits of pharmacologic venous thromboembolism prophylaxis in outpatients receiving chemotherapy but have not resulted in clear guidelines.
Use of the Khorana Risk Score to target patients at high risk who should receive chemical prophylaxis during ambulatory chemotherapy was endorsed by the American Society of Clinical Oncology and the National Comprehensive Cancer Network, but neither entity provides guidelines on how to use the Risk Score in clinical management.

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