Why is improving the diagnosis of extensiveness of ovarian cancer important?
Ovarian cancer is a disease with a high-mortality (death) rate. Many women (75%) are diagnosed when their disease is already at an advanced stage and 140,000 women die of this disease each year worldwide. Treatment consist of debulking surgery (removal of as much of the tumour as possible during an operation called a laparotomy - normally through a long vertical cut on the abdomen) and six cycles of chemotherapy. The order in which these two treatments are given depends on the extensiveness of disease (how widespread) and on the general health of the patient. The goal of debulking surgery is to remove all visible tumour or at least to leave no residual tumour deposit bigger than 1 cm in diameter. When the diagnostic evaluation suggests that the goal of debulking surgery could not be achieved, initial treatment may be three cycles of chemotherapy to first shrink the tumour, followed by debulking surgery and then further chemotherapy to complete the course of six cycles of chemotherapy.
To diagnose the extensiveness of disease by physical examination, ultrasonography, abdominal computed tomography (CT scan), and measurement of serum tumour(blood) markers are performed. An incorrect diagnosis could result in women having unsuccessful primary debulking surgery.
What is the aim of this review?
The aim of this review was to investigate if laparoscopy (keyhole surgery to look inside the abdominal cavity) is accurate in predicting whether a women can be successfully operated to remove of all visible tumour or at least to leave no tumour deposits larger than 1 cm. If so, this could help to avoid operating on those women who would be better treated with chemotherapy first.
What are the main results in this review?
The review included a total of 18 relevant studies, 11 of which were added for this update, and looked at 14 groups of women. In total 1563 women underwent a laparoscopy to evaluate the extensiveness of disease in the abdomen. Two studies concluded that laparoscopy was good at identifying those women in whom optimal debulking surgery was not feasible (with tumour deposits > 1 cm left after surgery) (low false positive rate for laparoscopy) and in all women the diagnosis was correct. However, even after a laparoscopy had suggested that optimal debulking surgery was feasible, some women had suboptimal primary debulking surgery where tumour deposits of > 1 cm were left). For every 100 women referred for primary debulking surgery after laparoscopy, between four and 46 will be left with visible residual tumour.
How reliable are the results of the studies in this review?
A limitation of this review is that only two studies performed diagnostic laparoscopy and then went on to attempt debulking laparotomy in all women. The other studies only performed a laparotomy when laparoscopy suggested that debulking to < 1 cm tumour residue was feasible. The correct diagnosis at laparoscopy is thereby not confirmed when > 1 cm tumour residue was predicted, this is called verification bias.
Who do the results of this review apply to?
Some studies used for this review also included women who underwent debulking surgery after chemotherapy or for recurrence. But mainly women were only included who were planned for primary debulking surgery. Therefore, the results presented in this review are applicable for all women who are scheduled for primary debulking surgery.
What are the implications of this review?
The studies in this review suggest that laparoscopy can accurately diagnose the extensiveness of disease. When performed after standard diagnostic work-up less women had unsuccessful debulking surgery and therefore resulting in less morbidity, Yet, there will still be women undergoing a laparotomy resulting in residual tumour of > 1 cm after surgery.
How up to date is this review?
The review authors searched for and used studies published from inception of databases until July 2018.
Laparoscopy may be a useful tool to identify those women who have unresectable disease, as no women were inappropriately unexplored. However, some women had suboptimal primary debulking surgery, despite laparoscopy predicting optimal debulking and data are at high risk of verification bias as only two studies performed the reference standard (debulking laparotomy) in test (laparoscopy)-positive women. Using a prediction model does not increase the sensitivity and will result in more unnecessarily explored women, due to a lower specificity.
This is an update of a Cochrane Review that was originally published in 2014, Issue 2.
The presence of residual disease after primary debulking surgery is a highly significant prognostic factor in women with advanced ovarian cancer. In up to 60% of women, residual tumour of > 1 cm is left behind after primary debulking surgery (defined as suboptimal debulking). These women might have benefited from neoadjuvant chemotherapy (NACT) prior to interval debulking surgery instead of primary debulking surgery followed by chemotherapy. It is therefore important to select accurately those women who would best be treated with primary debulking surgery followed by chemotherapy from those who would benefit from NACT prior to surgery.
To determine if performing a laparoscopy, in addition to conventional diagnostic work-up, in women suspected of advanced ovarian cancer is accurate in predicting the resectability of disease.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE via Ovid, Embase via Ovid, MEDION and Science Citation Index and Conference Proceedings Citation Index (ISI Web of Science) to July 2018. We also checked references of identified primary studies and review articles.
We included studies that evaluated the diagnostic accuracy of laparoscopy to determine the resectability of disease in women who are suspected of advanced ovarian cancer and planned to receive primary debulking surgery.
Pairs of review authors independently assessed the quality of included studies using QUADAS-2 and extracted data on study and participant characteristics, index test, target condition and reference standard. We extracted data for two-by-two tables and summarised these graphically. We calculated sensitivity and specificity and negative predictive values.
We included 18 studies, reporting on 14 cohorts of women (including 1563 participants), of which one was a randomised controlled trial (RCT). Laparoscopic assessment suggested that disease was suitable for optimal debulking surgery (no macroscopic residual disease or residual disease < 1 cm (negative predictive values)) in 54% to 96% of women who had macroscopic complete debulking surgery (no visible disease at end of laparotomy) and in 69% to 100% of women who had optimal debulking surgery (residual tumour < 1 cm at end of laparotomy).
Only two studies avoided partial verification bias by operating on all women independent of laparoscopic findings, and provided data to calculate sensitivity and specificity. These two studies had no false positive laparoscopies (i.e. no women had a laparoscopy indicating unresectable disease and then went on to have optimal debulking surgery (no disease > 1 cm remaining)).
Due to the large heterogeneity pooling of the data was not possible for meta-analysis.