Cytoreductive surgery (also called debulking) is a standard surgical procedure for advanced epithelial ovarian cancer. During surgery, the aim is to remove not only the ovaries, but also the uterus, fallopian tubes, and as much of the visible tumour as possible. Blood loss during cytoreductive surgery has long been recognised as a contributor to prolonged recovery time.
The aim of the review:
We evaluated the effectiveness and safety of tranexamic acid for reducing blood loss during cytoreductive surgery in women with advanced epithelial ovarian cancer. We searched for scientific research studies up to May 2015 and found only one randomised controlled trial ‒ considered the gold standard for study design ‒ that assessed a single dose of tranexamic acid given intravenously before the start of surgery versus a placebo in women undergoing cytoreductive surgery for clinically suspected advanced advanced epithelial ovarian cancer.
What are the main findings and conclusion?
Although tranexamic acid did numerically reduce blood loss, there was no clinical benefit, as the difference in blood loss was minimal, and there was no difference in need for blood transfusion, suggesting that this level of blood loss did not make a difference to the patient's well-being. Additionally, there was incomplete and limited evidence regarding tranexamic acid-related adverse events, so we can say little about whether tranexamic acid is safe for women with advanced ovarian cancer. The evidence we found from a single study was therefore insufficient to support routinely giving prophylactic tranexamic acid for cytoreductive surgery. This review indicates the need for future good quality, well-designed randomised controlled trials to provide more evidence on the effectiveness, safety and appropriate administration of tranexamic acid.
Quality of evidence:
The quality of the evidence was variable; therefore the overall the strength of the evidence reported in this review is low, as it is based on only one small randomised controlled study.
Currently, there is insufficient evidence to recommend the routine use of tranexamic acid for reducing blood loss in women undergoing cytoreductive surgery for advanced EOC, as only limited data are available from a single, low quality RCT at low overall risk of bias.
Ovarian cancer is the third most common gynaecological cancer worldwide, with an age-standardised incidence rate of 6.1 per 10,000 women. Standard therapy for advanced epithelial ovarian cancer (EOC) includes a combination of cytoreductive surgery and platinum-based chemotherapy. Cytoreductive surgery aims to remove as much of the visible tumour as possible. As extensive intraperitoneal metastases are typical of advanced EOC, cytoreductive surgery is usually an extensive procedure with the risk of excessive bleeding. Tranexamic acid given perioperatively is effective in reducing blood loss and allogeneic blood transfusion requirements in a variety of surgical settings. Therefore, tranexamic acid seems to be a promising agent for minimising blood loss and the need for blood transfusion among women with advanced EOC undergoing cytoreductive surgery.
To assess the effects of tranexamic acid for reducing blood loss associated with cytoreductive surgery in women with advanced EOC (stage III to IV).
We searched the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2015), MEDLINE, EMBASE and conference proceedings to May 2015. We also checked registers of clinical trials, citation lists of included studies, key textbooks and previous systematic reviews for potentially relevant studies.
We included randomised controlled trials (RCTs) comparing tranexamic acid given during surgery versus placebo or no treatment, in adult women diagnosed with advanced EOC.
Two review authors (CK, AS) independently selected potentially relevant trials, extracted data, assessed risk of bias, compared results and resolved disagreements by discussion.
We found only one study that met our inclusion criteria. This was a randomised double blind, placebo-controlled multicentre study conducted to evaluate the effectiveness of a single dose of intravenous tranexamic acid (15 mg/kg body weight) versus placebo, given immediately before surgery for reducing blood loss and the need for red blood cell transfusion. The mean total estimated blood loss was 668.34 mL and 916.93 mL for participants assigned to tranexamic acid and placebo groups, respectively. The mean difference (MD) of total estimated blood loss between the groups did not show a clinically important effect (MD − 248.59 mL; 95% confidence interval (CI) − 550.9 to 53.79; one study, 100 participants; moderate quality evidence). The mean number of transfused units of blood components was not different between the two groups (low quality evidence). There were no noted differences in the incidence of reoperation, readmission or thromboembolic events (very low quality evidence). We considered the methodology of the included study to be at low risk of selection, detection, and reporting biases. However, we were concerned about an imbalance of some baseline characteristics between the groups, and as there was no protocol for blood transfusion, the rate of blood transfusion may vary depending on the practice of each participating hospital.