Histopathological prognostic factors predicting para-aortic lymph node metastasis in patients with endometrioid uterine cancer

doi:10.1016/j.ygyno.2010.05.004

Gynecologic Oncology

Volume 118, Issue 2, 1 August 2010, Pages 151-154

https://doi.org/10.1016/j.ygyno.2010.05.004 Get rights and content

Abstract

Introduction

The purpose of this study was to determine histopathological factors for para-aortic lymph node (PALN) metastasis in patients with endometrioid uterine cancer.

Methods

A total of 355 patients (Stage I, n = 269; II, n = 24; and III, n = 62) (FIGO 2009) underwent primary radical surgery including complete systematic pelvic lymph node (PLN) and PALN dissection in Tohoku Gynecologic Cancer Unit (TGCU) between 1993 and 2004. Logistic regression analysis was used to determine the independent prognostic factors for PALN metastasis.

Results

Multivariate analysis revealed that PLN metastasis (p < 0.0001) and ovarian metastasis (p = 0.0080) related with PALN metastasis. Moreover, among the sites of PLN metastases, obturator lymph node (LN) [risk ratio (RR): 16.9, 95% confidence interval (CI): 4.3–66.4, p < 0.0001] and common iliac LN (RR: 7.1, 95% CI: 1.1–44.5, p = 0.0375) related with PALN metastases. In detection of PALN metastasis, combination of obturator LN and/or common iliac LN and/or ovarian metastasis (A) revealed 75.9% sensitivity (22/29) and 97.8% negative predictive value (NPV) (304/311). However, by combination of obturator LN metastasis and/or common iliac LN metastasis and/or grade 3 and/or deep myometrial invasion (B), the detection of PALN metastasis was 100.0% sensitivity (29/29) and 100.0% NPV (198/198). Also, 55.8% (198/355) of patients could have avoided PALN dissection by combination B.

Conclusions

These results suggest that PALN dissection is necessary when combination B is positive by pre- and intra-operative assessments. Further prospective randomized controlled studies need to be conducted in a larger patient population to establish the strategy for detecting PALN metastasis utilizing pre-/intra-operative assessments.

Introduction

Retroperitoneal lymph node metastasis is a critical prognostic factor for patients with endometrial carcinoma. The new International Federation of Gynecology and Obstetrics (FIGO) (2009) surgical staging system classifies endometrial carcinoma with metastasis to the pelvic and para-aortic lymph nodes as stage IIIC1 and IIIC2, respectively. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have recommended PLN and PALN dissection rather than nodal sampling in patients with endometrial cancer [1]. Less than only 39% of patients with metastasis to lymph nodes have grossly enlarged nodes [2], [3], [4], and 37% of LN metastases are 2 mm or less in diameter [5] in endometrial cancer. Therefore, it is important to perform complete pelvic lymph node (PLN) and para-aortic lymph node (PALN) dissection for assessing accurate surgical staging. The overall frequency of the PALN metastasis is 3.4–11.5% [3], [4], [6], [7], [8], [9], [10], [11]. Indication for PALN dissection should be based mainly on the risk of PALN metastasis. There are literatures that suggest the therapeutic significance of PALN dissection in patients with stage IIIC endometrial cancer [2], [6].

However, it may be excessive to perform complete PALN dissection because some have a low risk of PALN metastasis. From these points of view, it is important to select patients to perform PALN dissection. In Japan, 97.8% of the institutions which participate in the Japan Gynecologic Oncology Group (JGOG) routinely perform PLN dissection, and 93.5% of them perform PALN dissection either routinely (12.2%) or selectively based on tumor-related factors (81.2%) [12].

At present, there has been no standard method for selecting patients who do not need PALN dissection utilizing pre-/intra-operative assessments. The purpose of this study was to determine histopathological risk factors for PALN matastasis, and to evaluate the clinical validity of those factors to accurately select patients who requires PALN dissection.

Section snippets

Materials and methods

A total of 956 patients with endometrial cancer had primary surgery treatment in the Tohoku Gynecologic Cancer Unit (TGCU), involving 6 Universities and affiliated hospitals, between 1993 and 2004. Type II endometrial cancers (clear cell/serous adenocarcinoma) were excluded from this analysis. Also patients receiving pre-/post-operative radiation or neoadjuvant chemotherapy, and stage IV patients were excluded. Among them, 355 patients underwent primary radical surgical treatment, that is,

Results

Patient characteristics and the ratio of lymph node metastasis related with each histopathological risk factor are shown in Table 1. Median age was 54 years (range, 27–76 years). Of all the 355 patients, 7 patients (2.0%) had PALN metastasis alone. Five-year disease-related survival (DRS) in each stage was: stage IA, 98.3%; stage IB, 84.7%; stage II, 100.0%; stage IIIA, 87.5%; stage IIIC1, 77.7%; and stage IIIC2, 45.8%, respectively. There were no stage IIIB patients in this study.

Discussion

Indication for PALN dissection should be based mainly on the risk of PALN metastasis. The overall frequency of the PALN metastasis is 3.4–11.5% [3], [4], [6], [7], [8], [9], [10], [11]. Moreover, 28.6–66.7% of patients with PLN metastases have concomitant PALN metastases, and 0.7–2.0% with PALN metastasis alone [3], [4], [6], [7], [8], [9], [10], [11], [14], [15]. In our series, those were 8.2% (29/355), 52.4% (22/42), and 2.0% (7/355), respectively (Table 1). From this point of view, it may be

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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La cohorte de l’étude est constituée par toutes les patientes prises en charge dans notre établissement pour un cancer de l’endomètre quel que soit le stade, entre janvier 2000 et septembre 2012. Nous avons recueilli les données concernant la clinique (incluant les co-morbidités et l’indice de masse corporelle en kg/m²), l’imagerie préopératoire, la prise en charge chirurgicale, la classification FIGO et l’anatomopathologie. Les résultats anatomopathologiques ont été comparés avec les données de l’imagerie préopératoire.
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We found three cases (3/5) in which tumor invaded the deep myometrium among five para-aortic lymph node metastasis patients whereas there were only 21 cases (17.4%) in the other patients. Karube Y et al.12 found that ovarian metastasis and pelvic lymph node metastasis, particularly obturator and common iliac lymph node metastasis, was correlated to para-aortic lymph node metastasis. Benedetti Panici P et al.13 found that pelvic lymphadenectomy improved surgical staging, although preoperative stage I patients.
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We conducted a retrospective study on 244 cases of endometrioid uterine cancer that involved surgery in the Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, from January 2000 to May 2008. We conducted staging for each case to ensure accordance with FIGO 2009 surgical staging criteria. Clinical data, including histology, age at diagnosis, surgical procedure, adjuvant therapy, date of death or last follow-up, and date and sites of recurrence were collected for each patient.
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In most clinics pelvic lymph node (PLN) and para-aortic lymph node (PALN) dissection addition to TAH + BSO is a routine operative procedure at present [4,5]. On the other hand, performing PALN dissection in low risk patients have been reported to be overtreatment with increased morbidity [6,7]. However, there are not enough studies which have evaluated prognostic factors for predicting PALN metastasis [6–9].
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¹: These authors contribute equally to this work.

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