Elsevier

Gynecologic Oncology

Volume 97, Issue 3, June 2005, Pages 727-732
Gynecologic Oncology

Clinical significance of lympho vascular space involvement and lymph node micrometastases in early-stage cervical cancer: A retrospective case-control surgico-pathological study

https://doi.org/10.1016/j.ygyno.2005.01.004Get rights and content

Abstract

Objective

Several studies have shown that lympho vascular space involvement (LVSI) and lymph node micrometastases (LNmM) may be risk factors for recurrence in early-stage cervical cancer with no apparent lymph node metastases. We performed a retrospective case-control study to reassess whether the presence of lymph node micrometastases and LVSI is predictive of subsequent recurrence following surgical resection of early-stage cervical cancer.

Methods

In a series of 292 patients diagnosed with early cervical cancer and treated by the same surgical procedure (laparoscopic-vaginal radical hysterectomy) during the same time period, two paired series were selected. The first series consisted of 26 cases who recurred in a median time of 36.8 months and the second series were 26 cases matched for age, histological sub-type, surgico-pathological stage and maximal tumor diameter, who did not recur after a median follow-up of 122 months. Sections taken from the hysterectomy specimens were reassessed for LVSI. All the lymph node blocks which have initially been considered as uninvolved were submitted to serial sectioning. Immunohistochemical staining using anti-cytokeratins AE1 and AE3 was used for identifying LNmM.

Results

LVSI was twice more frequent and LNmM ten-fold more frequent in the group of patients who recurred: 20/26 (77%) versus 9/26 (35%) and 11/26 (42%) versus 1/26 (4%) respectively. The relative risk of recurrence is 2.64 (1.67–5.49, P < 0.01) in the presence of LVSI and 2.44 (1.58–3.78, P < 0.01) in the presence of LNmM. All the patients with LNmM were LVSI positive. At bivariate analysis, the true LNmM (deposits more than 200 um in size) was the only independent risk factor.

Conclusions

LNmM is an important risk factor of tumor recurrence in patients with early cervical cancer with no apparent lymph node metastases. LNmM seems to occur only in LVSI positive tumors. These data may lead to improve management of early-stage cervical cancer to reduce the risk of recurrence in those cases.

Introduction

In solid tumors at risk of lymphatic spread as colon cancer, melanoma, head and neck cancer, gastric cancer, oesophageal cancer, prostate cancer and lung cancer, the clinical significance of lymph node metastases (LNM) is generally accepted, but controversies still remain on the clinical significance of the so-called lymph node micrometastases (LNmM), i.e. metastases less than 2 mm in size. Some data are likely to demonstrate that LNmM are linked to a higher risk of post-surgical recurrence [1], [2], [3], [4], [5], [6], [7], [8], [9] whereas other studies do not [10], [11], [12], [13], [14]. In breast cancer, the prognostic implications of micrometastasis are currently being discussed [15], [16], [17], [18]. In the field of gynecological cancer, one retrospective cohort study [19] demonstrated that LNmM detected by immunohistochemistry was significantly more frequent in patients who had recurrence in the pelvic cavity after hysterectomy for apparently node negative endometrial cancer. Two similar studies [20], [21] have already demonstrated that putative LNmM detected by PCR were significantly more frequent in patient who recurred after radical hysterectomy for cervical carcinoma treated with radical hysterectomy.

Lympho vascular space involvement (LVSI) is found in 43% of early cervical cancers [22]. Its value as prognostic factor and its relationship with lymph node metastases are debated. The prospective surgical–pathological study conducted by the Gynecologic Oncologic Group [22], [23] considered LVSI as an independent prognostic factor in the same way as tumor size and depth of tumor invasion in patients affected by early-stage cervical cancer. But in a review of 25 publications, Creasman [24] denies any prognostic significance to LVSI found in primary tumor. Furthermore, the relation between LNmM and LVSI has not been evaluated in cervical cancer.

The aim of this retrospective case-control study was to assess the prognostic significance of LVSI and LNmM in early cervical cancer with no apparent lymph node micrometastases. In addition, we also determined the inter-relationship of these two putative prognostic factors. This study was performed with two matched cohorts of patients. The case series was made from all patients who recurred. The control series was made from equal number of patients randomly selected in the files of the patients who did not recur and were paired with the patients of the first series on classical oncologic criteria.

Section snippets

Patients

During the period December 1986 to October 2001, 292 patients affected by cervical cancer Stage IA2 (or Stage IA1 with patterns of LVSI) to IIB were submitted to Celio-Schauta [25] or Laparoscopically Assisted Radical Vaginal Hysterectomy (LAVRH). This operation is the equivalent of the radical abdominal hysterectomy. It starts with a systematic pelvic lymphadenectomy carried out with the laparoscope. The dissection includes the nodes situated in the lateral root of each parametrium and

Results

The two paralleled series were identical as far as age, histological type, pathological FIGO stage and tumor size are concerned (Table 1). LVSI was present in 20 of 26 recurrent cases (77%) and in 9 of 26 controls (35%) (P = 0.002). The total number of assessed nodes was 343 in the case series (mean: 13.8 ± 6.6 for each patient) and 425 in the control series (mean: 16.4 ± 8.6 for each patient). The difference is not statistically significant. A total of 18432 slides were assessed by the

Discussion

In our survey, LNmM was found in 11 of the 26 (42%) of the patients who recurred and in only one (4%) of the 26 women who did not. The relative risk of recurrence was estimated at 2.44 in the presence of LNmM (1.58–3.78). Even if the exclusions from the study are of a significant number, inclusion of these patients would have not modified our results. In fact, five patients were not evaluated because of missed lymphatic nodes blocks. These patients had similar prognostic factors (3 squamous

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