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