In this retrospective analysis we found that incomplete staging in EOC, performed by gynecologic oncologists, is most often due to insufficient biopsies of different locations of the peritoneum (n = 34; 68%), and less than ten lymph nodes being resected and/or found at pathology (n = 16; 32%). The most mentioned reasons for not performing biopsies were forgetting to do so, and believing that, after careful inspection and palpation, taking biopsies is irrelevant and/or biopsies already are being taken while performing a hysterectomy (peritoneum of the cul-de-sac, broad ligament and bladder). Forgetting to take blind biopsies was registered in 11 cases and there can be little excuse to justify such negligence.
Previous studies, mainly focused on patients treated before 2000, report incidences of incomplete staging up to 85% [3,5,6,9]. In the majority of these patients no or inadequate lymph node resection was performed . But also no or an insufficient number of random peritoneal biopsies was frequently found. These studies conclude that lack of specialized skills and/or knowledge of the gynaecologist might be a possible explanation for incomplete staging [3,5,6,10]. However, in the present study only gynaecologic oncological center hospitals were included, (of which one can assume that they do have the skills and knowledge that is required), taking blind biopsies was simply forgotten in about one third (11/34) of the incomplete biopsy cases. A standardized surgical report, and check lists with all parts of the staging procedure according to the FIGO guidelines available in the operation rooms, might be a solution to forgetting parts of the procedure.
The assumption that taking blind biopsies is unnecessary is a different matter. In a recent review on surgical staging of EOC the average yield of positive blind biopsies of the peritoneum in a number of studies was around 8% . It has also been argued that upstaging of EOC on the basis of positive blind biopsies is lower but this would be true for all the different staging steps and data on this specific issue are scarce . Ayhan et al. found microscopic disease in random peritoneal biopsies or appendectomy in 7.1% of 127 EOC patients . Shroff et al. had similar results in that microscopically positive biopsies from normal-appearing tissue were found in 6/122 patients (5%) . Five of these six patients were upstaged by random biopsies alone. Taking a more general perspective over the debate of percentages it has been argued that random peritoneal biopsies remain indicated in early-stage disease owing to the low morbidity of the procedure and the present possibility of upstaging and altered management. Furthermore, systematic peritoneal biopsies ensure careful palpation and examination of all surfaces. The latter notion is the more important in view of the recent trend to perform staging of EOC laparoscopically, therewith losing the contribution of palpating subperitoneal abnormalities.
Adequate lymph node sampling appears to be an essential part of the staging procedure in clinical early stage EOC. In a review on lymph node metastases, the overall incidence varied from 6.1–29.6% (mean 14.2%) . Despite its importance, the reported incidence of lymph node staging worldwide varies between 10% and 30% . In a recent report on lymph node staging in The Netherlands, the incidence of lymph node dissection improved from 26% in 2000 to 67% in 2012. Moreover, the percentage of patients from whom 10 or more lymph nodes were removed also increased during the study period (from 2.3–47.6%) .
In the present study, in 16 patients with an incomplete staging procedure (32%), either no lymph nodes were resected or the number of lymph nodes identified was below ten. Various reasons for this were mentioned by the gynecologists. First of all, in five patients no lymph nodes were resected because it had no therapeutic consequences according to the gynecologist (already indication for adjuvant chemotherapy). In another four patients it was mentioned that the procedure was technically impossible, mainly related to intense intra-abdominal adhesions, extensive bloodloss and/or obesity. Secondly, although according to the gynecologist enough tissue at the different pelvic and paraaortal locations were sampled, the number of lymph nodes identified by the pathologist were less than ten, hence insufficient according to the Dutch guideline. This could be partly explained by the fact that in five patients pelvic lymph nodes were obtained only at the ipsilateral side. In 25 patients (50%), including these five patients, the value of a contralateral pelvic lymphadenectomy in case of a unilateral ovarian tumor was questioned and therefore omitted. In the already mentioned review examining the incidence and locations of lymph node metastases in early stage EOC, 20% of all lymph node metastases were located at the pelvic regions only. Only contralateral lymph node metastases of a unilateral tumour was found in 16% of positive pelvic nodes and 11% of positive paraaortic nodes . These findings provide a strong argument against an ipsilateral node dissection only.
Besides the resection of not enough fatty tissue containing the lymph nodes by the gynecologist, the pathologist examining the tissue resected may influence the definite number of lymph nodes recognized. In a study that observed the impact of nodal retrieval after educating the pathologist, found that extra education about the importance of nodal count significantly raised the nodal count at pathology . New pathological methods are being investigated and have shown promising results. Svec et al. showed that re-fixing in a lymph node revealing solution containing ethanol, diethyl ether, glacial acetic acid and formalin, increased the number of revealed lymph nodes in colorectal resection specimens . In another study comparing standard formalin fixation with fat-clearing by acetone in specimens after gastrectomy, more lymph nodes were found using aceton, though this was not statistically significant. More high quality trials are needed to study the optimal technique for retrieving lymph nodes at pathology.
Complete staging has been proven to be an important prognostic factor in EOC [4,16]. There is evidence that, in contrast to incompletely staged patients, adjuvant chemotherapy in completely staged patients does not improve survival and should be omitted [4,16,19,20]. This argument makes a comprehensive and complete surgical staging the more important. Our study demonstrates that the staging quality in daily life practice is still too low. We have analyzed the reasons for this and these data might serve to improve the staging performance of EOC. It should be said that the low percentages of complete surgical staging of EOC according to the existing guidelines might be flattered. In our study we found some reasons of the gynecologic oncologists for deliberately omitting certain staging steps in the individual clinical situation, perfectly plausible. In 34 patients the taking of blind peritoneal biopsies was incomplete. Of these, taking the biopsies was considered to have no therapeutic consequences in six patients, there were technical problems in three patients and comorbidity problems or a second malignancy in two. Together they represent one third of the incomplete biopsy group.
In 16 patients the yield of lymph nodes was incomplete with technical problems in four and no therapeutic consequences also in four. To convict these cases as victims of inadequate surgical performance would be unfair. For this reason a plea has been made by Bense et al (2019, in press) to consider cases such as these separately from the categories complete and incomplete staging and the term ‘considerate adjustment of staging procedure (CASP)’ has been proposed. It might be worthwhile to include this category in future studies on staging of EOC.