Fast track — ArticlesSize 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
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
References (23)
- et al.
The importance of the groin node status for the survival of T1 and T2 vulval carcinoma patients
Gynecol Oncol
(1995) - et al.
Carcinoma of the vulva. FIGO 6th annual report on the results of treatment in gynecological cancer
Int J Gynaecol Obstet
(2006) - et al.
Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective East Carolina University/Anne Arundel Medical Cancer Sentinel Node Multicenter Study
J Am Coll Surg
(2009) - et al.
Presentation, management and outcome of axillary recurrence from breast cancer
Am J Surg
(2000) - et al.
Prognostic value of pathological patterns of lymph node positivity in squamous cell carcinoma of the vulva stage III and IVA FIGO
Gynecol Oncol
(1992) - et al.
Occult lymph node metastases in early stage vulvar carcinoma patients
Gynecol Oncol
(2005) - et al.
Interpretive disparity among pathologists in breast sentinel lymph node evaluation
Am J Surg
(2003) - et al.
Sentinel node dissection is safe in the treatment of early-stage vulvar cancer
J Clin Oncol
(2008) - et al.
Sentinel lymph node investigation in melanoma: detailed analysis of the yield from step sectioning and immunohistochemistry
J Clin Pathol
(2004) - et al.
Metastasis detection in sentinel lymph nodes: comparison of a limited widely spaced (NSABP protocol B-32) and a comprehensive narrowly spaced paraffin block sectioning strategy
Am J Surg Pathol
(2009)
Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva
J Clin Oncol
Cited by (217)
British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: An update on recommendations for practice 2023
2024, European Journal of Obstetrics and Gynecology and Reproductive BiologyA comparison of ICG-NIR with blue dye and technetium for the detection of sentinel lymph nodes in vulvar cancer
2023, European Journal of Surgical OncologyInvasive cancer of the vulva
2023, DiSaia and Creasman Clinical Gynecologic OncologyPreoperative predictors of inguinal lymph node metastases in vulvar cancer – A nationwide study
2022, Gynecologic OncologyCitation Excerpt :All vulvar cancer patients were treated by a team of surgeons with special interest in vulvar cancer. The treatment was standardized and performed according to the GROINS-V I [10,25] protocol on the SN procedure and the national Danish guidelines on vulvar cancer securing a uniform work-up and treatment strategy. All pathological examinations were performed by pathologists with a special interest in gynaecological oncology.