Relevance of Pelvic and Para-aortic Node Metastases in Early-stage Ovarian Cancer

Discussion

The impact of node involvement in primary early-stage ovarian cancer is still unclear (3, 4). There are currently no data of prospective studies evaluating the impact of lymphadenectomy in early-stage ovarian cancer. Di Re et al. found that the incidence of metastatic lymph nodes significantly increased with advanced stages, serous histology and greater amount of residual tumor (4-6). Possibly the prognostic influence of node involvement plays a greater role in the early stages than in advanced stages, in which the residual tumor mass has greater prognostic impact (5, 6). Nevertheless, the probability of having node metastases is lower in early stages than in advanced stages (7, 8). Even in our collective 8% of patients had node metastases in early ovarian cancer (Table I). Risk factors for node metastases were serous cancers and histologic grade 3 (18) (Table II). On multivariate analysis, grade 3 tumors, serous and endometrioid histology were independent predictors for lymph node metastases in T2 ovarian cancers, respectively (Table II).

Several studies describe that both node metastases in the pelvic and para-aortic lymph nodes, as well as node metastases in the pelvic or para-aortic region can only be found in early ovarian cancer in about 20% of cases (10-12), as seen in our study (Table I). Our collective involved nodes in the pelvic and para-aortic region in T1 and T2 (Tables II and III); even one patient had para-aortic lymph node metastases only, without any involvement of the pelvic region (Table III). Our collective showed the following pattern: 4 patients had affected pelvic nodes, out of which one patient had even additionally affected para-aortic nodes (Table III). These results are comparable to the work of Chang et al., with detection of lymph node metastases in T1 and 2 ovarian cancer patients (9).

In our collective, serous cancers showed a distribution pattern of node involvement with combined or isolated affection of the pelvic and/ or para-aortic region (Table III); Mucinous cancers showed affection of the pelvic nodes without affection of the para-aortic nodes; additionally one patient with endometrioid cancer presented an isolated affection of the para-aortic nodes (Table III). None of the patients with non-serous cancers showed both an affection of pelvic and para-aortic nodes (Table III).

Overall, studies showed a rate of about 45% to 59.1% of node involvement in advanced ovarian cancer patients (13). The prognostic impact of systematic lymphadenectomy in the initial surgical management in primary advanced ovarian cancer is still unclear (11). The randomized trial of Panici et al. described that systematic lymphadenectomy improves PFS, but not survival in women with optimally debulked advanced ovarian cancer compared to resection of bulky nodes (11, 13).

Abe et al. did not notice an advantage for OS and PFS for patients after lymphadenectomy in the early stages compared to the renunciation of the lymphadenectomy (14). Possibly the positive impact of lymphadenectomy in early FIGO stages is caused by removing the positive nodes and patients without lymphadenectomy in early stages could have clinically-inapparent positive nodes and were staged to FIGO I/II (10). Studies showed that patients that were upgraded to FIGO IIIC due to detection of positive nodes had similar OS compared to FIGO I patients (11). According to the current FIGO classification, published in January 2014, patients with positive retroperitoneal lymph nodes and T1/T2 N1 M0 are staged up to FIGO IIIA1 (15, 16).

This fact supports the hypothesis that adequate staging can be achieved with lymphadenectomy and possibly a positive prognostic impact can be reached in early-stage ovarian cancer. The removal of positive lymph nodes in the pelvic or para-aortic region could explain the positive prognostic influence of the performed lymphadenectomy in early stages (4, 17). Possibly this impact is caused by involved nodes in the para-aortic region that are not removed by isolated pelvic lymphadenectomy alone. Chang et al. described affection of para-aortic nodes and recommended a para-aortic lymphadenectomy up to the renal vessels that may detect occult metastases and can help tailor appropriate adjuvant treatment, as well as offer useful prognostic information (9).

Most often serous cancers lead to node involvement in pelvic and para-aortic nodes, but even non-serous cancers like endometrioid and mucinous cancers lead to node metastases in pelvic and para-aortic nodes. Node positivity is uncommon for patients with early-stage ovarian clear cell carcinoma (18); in our study no patient of this subgroup showed node metastases. Node involvement in this sub-group leads to worse prognosis (18), therefore lymphadenectomy seems to have a prognostic impact and leads to an adequate staging with detection of occult node metastases.

It is still unclear if lymphadenectomy in the early stages is reasonable in all patients and if a systematic pelvic and para-aortic or a pelvic lymphadenectomy should be performed. Prospective studies need to investigate the prognostic impact of lymphadenectomy in early-stage ovarian cancer, perhaps depending on histology and distribution pattern of node metastases. If a supplementary preoperative PET examination is useful to optimize the staging and to detect patients who might benefit from lymphadenectomy is still unclear. One study showed that 18F-FDG PET/CT is an accurate tool for the detection of nodal metastases in early ovarian cancer (2).

Our findings suggest the possibility, that pelvic and para-aortic lymphadenectomy in early ovarian cancer leads to an adequate staging and might detect occult node metastases (Table II). Prospective studies may benefit from investigating the clinical implications of our results. Consequently, the efficacy of systematic lymphadenectomy on prognosis in early ovarian cancer is still unknown due to the lack of prospective randomized controlled studies.