Main findings
We found that 18.7% of clinically FIGO stage I-II EOC patients are
upstaged based on comprehensive surgical staging. The individual
estimates from the included 23 studies varied widely, ranging from 4.5%
up to 38.5%, highlighting the need for a pooled approach to increase
accuracy. The result of this study enables clinicians to more accurately
inform patients on the staging utility and clinical consequences of
their planned surgery. This can be further stratified according to
individual patient characteristics in FIGO stage, histology and tumor
differentiation. The upstaging rate increases to 23.0% in those
patients suspected of stage I EOC. The stage II EOC patients seem to
reduce the overall risk, however, in this subgroup less tumor positive
sites (e.g., uterus involvement) will lead to upstaging that in stage I.
Notably, those with a high grade tumor (40.9%), and serous EOC
(35.3%), yielded a high probability of upstaging. We have pooled the
data of grade II and III tumors into high grade tumors to ensure
translation to the clinical practice. In contrast to what we expected,
and based on a limited number of cases, clear cell carcinoma of the
ovary was not associated with a substantial upstaging risk (11.2%)
relative to the overall risk of 18.7%. While certain low-risk groups
exist, we could not identify any subgroup in which a staging surgery can
be safely omitted based on an absent benefit.
This meta-analysis provides insight into the tumor positivity rate, and
the upstaging contribution of each component encompassing surgical
staging. The tumor positivity was identified in uterus, cytology,
peritoneal biopsies, omentum, and the appendix in 6.2%, 18.4%, 9.7%,
5.2%, and 3.6% of EOC patients, respectively, with corresponding
upstaging rates of 5.9%, 8.5%, 3.5%, 3.9%, and 1.6%. Remarkably,
results on tumor involvement of the uterus, and the contralateral ovary
are only scarcely reported in the included studies. This is a limitation
across the retrieved studies, and particularly restricts the ability to
preoperatively assess the understaging risks in young women where
fertility-sparing surgery is considered.
Lymph node assessment resulted in 8.7% upstaging, whereas this
increased to 12.0% when mucinous EOC cases were excluded. This was
decided based on previous reports on the rare lymphatic metastatic
dissemination of mucinous EOC, at approximately 0.8% found at
staging38. When specified upon lymph node level,
para-aortic lymph nodes are more often affected with 6.8% upstaging,
than pelvic lymph nodes with 4.2%. The impression might be given that
the combined upstaging risk for both positive pelvic and para-aortic
lymph nodes is higher relative to the calculated overall risk of 8.7%.
However, a subgroup of patients (2.3%) had metastases in both their
pelvic and para-aortic lymph nodes. Furthermore, the included studies
differed between the data analyses, possibly contributing to a variation
in results.
Unfortunately, the terms lymph node sampling, dissection, and
lymphadenectomy were used interchangeably within the included
literature. A metaregression was used to study whether an association
between the number of resected lymph nodes – regardless of the name
used for the type of structured nodal assessment – and the upstaging
rate. This did not yield a significant association, though this can
possibly be attributed to insufficient statistical power as it was based
on ten included studies. When multivariately adjusted for the study
period of each individual study, assuming that recent studies would
routinely use a CT based nodal assessment preoperatively, the results
remained not significant.