Prognostic significance and risk factors for pelvic and para-aortic lymph node metastasis in type I and type II ovarian cancer: a large population-based database analysis

In previous studies, the target for biopsy or lymphadenectomy largely depended on the size of the lymph nodes. However, size is not a reliable indicator of the status of nodal involvement [17, 18]. Currently, whether to perform lymph node dissection generally depends on clinicopathological data. Previous studies have identified multiple factors that affect the risk for lymph node metastasis. Factors shown to increase risk include grade, serous histology, CA125 level, bilateral primary lesion, positive cytologic washings, and ascites [19,20,21]. However, the amount of data in these studies was not sufficient. The prognostic impact of clinicopathological factors associated with node involvement should be investigated in larger studies to improve the prognostic relevance of node metastasis. The current study utilized data collected from the SEER database to explore the risk factors and prognostic value of lymph node metastasis and to differentiate these findings in a two-tier classification system.

Risk factors for PLN and PALN metastasis in OC

In this series, our results showed that the occurrence of lymph node metastases is lower than that reported in the previous literature [11, 22, 23]. According to the traditional view, PALN metastasis is commonly understood as the initial route, with the pelvic nodes constituting a second metastatic site [23, 24]. However, in each tumour stage of the SEER data, the frequency of lymph node metastasis in the para-aortic basin is similar to that of the pelvic basin from tumour stage T1 to tumor stage TxM1. Through multivariate analysis, tumour stage was confirmed as an independent risk factor for node involvement in our study, in accordance with the data in previous studies [25]. The higher that the tumour stage is, the greater that the chance is of lymph node metastasis. Thus, considering the extremely low rate of positive lymph nodes at tumour stage T1, the benefits of lymphadenectomy should be weighed in this group, especially in the type I group. In the higher tumour stage T2-TxM1, lymph nodes should be screened throughout the pelvic and para-aortic regions to maximize the chance of finding positive lymph nodes.

There is accumulating evidence that G3 is a risk factor for lymph node metastasis [20, 26, 27]. However, the pathological grading system was not always a risk factor in this analysis, in contrast to the data in the literature [19, 26]. Thus, utilizing the pathological grade system retains limited function in the ability to detect those at risk for nodal disease. New classifications should be explored.

PLN and PALN metastasis in type I and type II OC

According to histologic pathogenesis, molecular alterations, and clinicopathologic features, the classification of ovarian cancers includes two distinct subtypes. Whether from a clinical perspective or molecular alterations, type I is different from type II [28,29,30,31,32,33,34]. Based on these different aspects, the two types should have stratified treatment plans. However, there is currently no research that differentiates the role of lymph node metastasis between the two subtypes. The uniqueness of the current study lies in its stratification of patients not only by traditional pathologic factors but also by the two-tier system. In our cohort, the incidences of PLN, PALN and PLN + PALN metastasis in type II patients were almost threefold higher than those in type I patients. In multivariate analysis, compared to type I, type II was a significant and independent risk factor for PLN and PALN involvement. These observations support the hypothesis that these cancers metastasize through different pathways and represent distinct clinical entities. According to these observations, it seems appropriate to determine the strategy for lymph node dissection in cases of ovarian cancer according to the type of primary tumour. Type II disease, especially tumour stage > T1, should be treated with lymph node dissection as much as possible. Within each type, there was no difference between PLN and PALN involvement, indicating that there was no pattern in the location of nodal disease.

To explore the important role of the two-tier system in behaviour and biology, the other important issue is to determine whether the risk factors are similar for the two tumour subtypes. The most noteworthy finding of this study was that the risk factors vary according to the type. In other gynaecologic tumours, age and tumour diameter are significant risk factors [21, 35]. However, the roles of age and tumour size in type I were not always the same as those in type II. For PLN involvement in type I cases, beyond advanced tumour stage, there were no other risk factors. However, in the type II group, G3 enhanced the risk, and tumour size > 20 cm reduced the risk. In PALN involvement, G3 also enhanced the risk, but tumour size was not a significant and independent risk factor for node positivity in either the type I or type II group. For PLN + PLAN status, age ≥ 50 y and tumour size > 10- ≤ 15 cm reduced the risk of lymph node metastasis in the type II group. However, they were not significant and independent risk factors for type I. Based on these findings, there is no reason to believe that older patients or patients with larger tumours have a tendency towards lymph node metastasis.

Survival rates of PLN and PALN metastasis in type I and type II OC

For the entire cohort, the patients with PALN involvement had a significantly more favourable prognostic impact (CSS/OS) than those with PLN and PLN + PALN involvement. However, we should consider that there are different types of ovarian cancer. In type I patients, the survival rate of PALN-positive patients is not better than that of PLN-positive patients and is worse when considering the 10-y OS or CSS. Conversely, the patients with PALN involvement compared to those with PLN metastasis had a significantly more favourable prognosis in type II disease. When predicting the effect of positive lymph nodes on survival, we should first consider the two-tier stratification.

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