VTE risk in patients with ovarian cancer undergoing neoadjuvant chemotherapy.

Ovarian cancer is the ninth most common type of cancer and the seventh most common cause of cancer death in women [1]. In 2020, the estimated incidence was 6.6 per 100,000 women and the mortality was 4.2 per 100.000 women worldwide [1].

The median age at diagnosis is 63 years, and the 5-year survival is 49.1% [2]. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), which explains the poor prognosis [3].

For a long time, the treatment consisted of a first surgery as complete as possible followed by adjuvant chemotherapy and a second surgery, if possible. However, in the 2000s neoadjuvant chemotherapy (NACT) was introduced to decrease the tumor volume, improve the surgery results, and reduce postoperative complications [4].

Ovarian cancer carries a high risk of venous thromboembolism (VTE) events, and chemotherapy is a well-known significant risk factor for VTE [5, 6]. Women treated with NACT have a particularly elevated risk of VTE.

NACT, ovarian cancer and VTE

In a large Korean cohort study comprising 26,863 women newly diagnosed with ovarian cancer, the incidence and risk of VTE were highest in women who underwent chemotherapy and surgery with NACT as a primary cancer treatment. In total, 536 per 10,000 women who underwent NACT experienced VTE, compared to 360 per 10,000 women who underwent adjuvant chemotherapy and 132 per 10,000 women who had only surgery [7].

In two retrospective cohort studies of patients with ovarian cancer receiving NACT, VTE risk during the primary treatment period was 18–27% [8, 9]. A total of 8–12% were diagnosed with VTE during NACT, 3–6% during the immediate postoperative period following interval debulking (IDS), and 3–10% during subsequent adjuvant chemotherapy [8, 9].

The risk in women undergoing NACT might be higher also because of the higher cancer and/or comorbidity burden that prompts the decision to defer primary surgery.

A single-center retrospective cohort study evaluated the incidence of VTE in patients with newly diagnosed, pathologically verified ovarian, fallopian tube, or primary peritoneal cancer receiving NACT [10]. Patients had a median age of 69.1 (range 42.6–92.6) years, 69.1% presented with stage IV disease, and the predominant histology was high-grade serous carcinoma (83.3%) [10].  In total, 43.8% of patients presented a baseline Khorana score of 1, while 39.1% and 16.8% of patients presented a baseline Khorana score of 2 and ≥3, respectively [10]. Among the 299 patients, 25.9% experienced at least one episode of VTE, with the highest rate of events (13.8%) at the first visit/before induction of NACT. The second peak of VTE events occurred during NACT (9.3%) [10].

No association between demographic characteristics or Khorana score and VTE

The study did not show any association between the occurrence of a new VTE and the patient’s age, tumor histology, or germline mutation status. In addition, there was no difference in VTE rates during NACT between patients that had a Khorana score of <2 versus Khorana scores ≥2 (40.7% vs 59.3%; p=0.8, respectively) [10].

This indicates that the Khorana score is not predictive and applicable in patients with ovarian cancer who undergo NACT. Patients with ovarian cancer receiving NACT had an almost three-times higher risk of VTE than the highest risk population in the Khorana algorithm, and 40% of the new-onset VTE events occurred in patients with Khorana scores of <2 [10].

In addition, demographic characteristics seem not to affect the risk of VTE for patients with ovarian cancer undergoing NACT.

A retrospective review showed that of all women undergoing NACT for FIGO (International Federation of Gynecology and Obstetrics) radiological stages III and IV, 15.1% developed VTE from the start of NACT. In addition, most women developed pulmonary embolism. Age, BMI, smoking, or other comorbidities were not significantly associated with VTE risk [11].

VTE impact on IDS

VTE has a potentially negative impact on the rate of IDS.

A retrospective review of women with a primary ovarian, fallopian tube, or peritoneal cancer who received NACT found a VTE incidence during NACT of 28%. In addition, 64% of patients experienced a pulmonary embolism. Most patients had stage II disease and serious adenocarcinoma, which increased VTE risk [12].

VTE may delay the administration of potentially lifesaving chemotherapy or lead to the cancellation of IDS, despite its importance in treating advanced-stage ovarian cancer. As a matter of fact, in this study, significantly fewer patients with VTE were candidates for IDS (60% vs 88%, p=0.005) [12].

A single-center retrospective review highlighted that women with ovarian cancer receiving NACT and not undergoing IDS have a >3-fold increase in mortality compared to those who have IDS, even after adjustment for age, comorbidities, and dose reduction NACT [13].

Conclusion

Given the high prevalence of VTE at diagnosis and incidence during treatment and the increasing use of NACT as primary ovarian cancer treatment, medical prophylaxis throughout primary treatment is worth consideration.

There is currently no guideline for universal VTE prophylaxis in patients with ovarian cancer who are initiating chemotherapy. ASCO guidelines suggest the use of chemoprophylaxis in selected patients with high-risk ambulatory cancer but recommend against routine use [14].

Researchers and clinicians should evaluate the risk of VTE at the time of ovarian cancer diagnosis. In addition, randomized controlled trials of prophylactic anticoagulation during NACT in ovarian cancer should be strongly considered

 

References

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