Elsevier

The Lancet Oncology

Volume 11, Issue 7, July 2010, Pages 646-652
The Lancet Oncology

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Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study

https://doi.org/10.1016/S1470-2045(10)70104-2Get rights and content

Summary

Background

Currently, all patients with vulvar cancer with a positive sentinel node undergo inguinofemoral lymphadenectomy, irrespective of the size of sentinel-node metastases. Our study aimed to assess the association between size of sentinel-node metastasis and risk of metastases in non-sentinel nodes, and risk of disease-specific survival in early stage vulvar cancer.

Methods

In the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V), sentinel-node detection was done in patients with T1–T2 (<4 cm) squamous-cell vulvar cancer, followed by inguinofemoral lymphadenectomy if metastatic disease was identified in the sentinel node, either by routine examination or pathological ultrastaging. For the present study, sentinel nodes were independently reviewed by two pathologists.

Findings

Metastatic disease was identified in one or more sentinel nodes in 135 (33%) of 403 patients, and 115 (85%) of these patients had inguinofemoral lymphadenectomy. The risk of non-sentinel-node metastases was higher when the sentinel node was found to be positive with routine pathology than with ultrastaging (23 of 85 groins vs three of 56 groins, p=0·001). For this study, 723 sentinel nodes in 260 patients (2·8 sentinel nodes per patient) were reviewed. The proportion of patients with non-sentinel-node metastases increased with size of sentinel-node metastasis: one of 24 patients with individual tumour cells had a non-sentinel-node metastasis; two of 19 with metastases 2 mm or smaller; two of 15 with metastases larger than 2 mm to 5 mm; and ten of 21 with metastases larger than 5 mm. Disease-specific survival for patients with sentinel-node metastases larger than 2 mm was lower than for those with sentinel-node metastases 2 mm or smaller (69·5% vs 94·4%, p=0·001).

Interpretation

Our data show that the risk of non-sentinel-node metastases increases with size of sentinel-node metastasis. No size cutoff seems to exist below which chances of non-sentinel-node metastases are close to zero. Therefore, all patients with sentinel-node metastases should have additional groin treatment. The prognosis for patients with sentinel-node metastasis larger than 2 mm is poor, and novel treatment regimens should be explored for these patients.

Funding

None.

Introduction

Introduction of the sentinel-node procedure is one of the most promising recent advances in surgical management of early stage squamous-cell cancer of the vulva: we have previously shown that inguinofemoral lymphadenectomy can be avoided when the sentinel node is negative for disease, resulting in a significant decrease in morbidity.1

Pathological ultrastaging (multiple sectioning and immunohistochemistry) is typically done on excised sentinel nodes, and substantially improves detection of sentinel-node metastases.2, 3 For most patients with vulvar cancer with a positive sentinel node, metastases in the non-sentinel nodes are absent.4, 5 In patients with breast cancer, micrometastases are defined by size, with the maximum dimension of the largest lymph-node tumour no larger than 2·0 mm. Submicrometastases are no larger than 0·2 mm.6 Patients with breast-cancer with micrometastases in the sentinel node have a significantly lower risk of non-sentinel-node involvement compared with patients with macrometastases.7, 8, 9 In the tumour-node-metastasis (TNM) classification for breast cancer, submicrometastases are classified as N0 and patients are treated as lymph-node negative. Patients with cutaneous melanoma with micrometastases smaller than 0·1 mm also have a lower risk of non-sentinel-node involvement than those with larger sentinel-node metastases and the same prognosis as sentinel-node negative patients.10 In vulvar cancer, comparable data are not available and, until now, no distinction has been made between micrometastases and macrometastases with regard to additional treatment.

The presence or absence of inguinofemoral lymph-node metastases is the most important prognostic factor in vulvar cancer;11, 12, 13 however, the absence of prospective data has led some to question the clinical significance of micrometastases in sentinel nodes. In the GROningen INternational Study on Sentinal nodes in Vulvar cancer (GROINSS-V), all early stage vulvar-cancer patients with a positive sentinel node (found by routine pathology or pathological ultrastaging) were routinely scheduled for inguinofemoral lymphadenectomy. Pathological ultrastaging was included in the original study protocol and was done when the sentinel node was found to be negative on routine haematoxylin and eosin examination.

The aim of the present study was to assess the association between size of sentinel-node metastasis and risk of metastases in non-sentinel nodes, as well as disease-specific survival, in patients with early stage vulvar cancer. We compared the risk of non-sentinel-node involvement and disease-specific survival in patients with a positive sentinel node found by routine pathology versus ultrastaging, since metastases identified by routine examination are larger than those identified by ultrastaging. This analysis was done for all GROINSS-V patients (n=403). We also did a pathology review, which allowed a more detailed analysis of absolute size of sentinel-node metastases in relation to the risk of non-sentinel-node involvement and disease-specific survival.

Section snippets

Patients

A prospective multicentre observational study (GROINSS-V) was done in patients with early stage squamous-cell vulvar cancer (diameter <4 cm) between 2000 and 2006. Central data management was done at the University Medical Center Groningen, Netherlands. Treatment consisted of excision of the primary tumour and the sentinel-node procedure (using radioactive tracer and blue dye). In case of a positive sentinel node, the protocol specified inguinofemoral lymphadenectomy by separate incisions.

Results

From March 6, 2000, until June 7, 2006, 403 eligible patients underwent the sentinel-node procedure according to the GROINSS-V protocol. In 135 (33%) of 403 patients (164 groins) original pathological assessment showed metastatic disease in one or more sentinel nodes. The baseline characteristics of these 135 patients are summarised in table 1. Frozen sectioning was done in 315 (78%) of 403 patients and showed a sensitivity of 48% (95% CI 38–57), specificity of 100% (98–100), negative

Discussion

The results of this study suggest that identification of sentinel-node metastasis in early stage vulvar cancer necessitates further groin treatment, regardless of the size of the metastasis. We did not find a cut-off size for sentinel-node metastasis below which the risk of additional groin metastases becomes negligible.

To our knowledge, this is the first study to investigate the association between risk of non-sentinel-node metastases and size of sentinel-node metastases in vulvar cancer. In

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