By Robert L. Coleman, MD. Professor, University of Texas; M.D. Anderson Cancer Center, Houston. Dr. Coleman reports no financial relationships relevant to this field of study.
Synopsis: Among women with early-stage squamous cell carcinoma of the vulva, sentinel node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy. Histological ultrastaging is an important adjuvant to sentinel node assessment for metastatic disease.
Source: Levenback CF, et al. Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: A Gynecologic Oncology Group study. J Clin Oncol 2012;Jul 2 [Epub ahead of print].
This article originally appeared in the October 2012 issue of OB/GYN Clinical Alert.
Sentinel lymph node biopsy is an assessment tool for early metastatic nodal spread used in management of many solid tumors. To evaluate its safety as a replacement for inguinal femoral lymphadenectomy (IFN), a multi-institutional clinical trial was conducted proscribing sentinel lymph node (SLN) biopsy ahead of full IFN in women with early-stage vulvar cancer. Eligible patients were to have invasive (≥ 1 mm) squamous cell carcinoma of the vulva between 2 and 6 cm in size and clinically non-suspicious groin nodes. Sentinel lymph node localization was performed using dye and radionuclide with optional lymphoscintigraphy. Identified SLNs were prepared using step sectioning and stained for cytokeratin using immunohistochemistry (IHC). In all, 452 patients underwent the procedure with SLNs being identified in 418 (92%). Nodal metastases were identified by routine pathological assessment in 102 and by IHC in 30 additional patients (node metastasis rate 29%). Among those where a SLN was identified, the false-negative rate (SLN histologically negative, but metastatic nodal disease positive on IFN) was 8% (11/132). The false-negative predictive value, a metric that also includes the majority population of true-negative assessments (1-negative-predictive value) was 3.7%. In women with primary tumors < 4 cm in size, the false-negative rate was 2%. The authors conclude that the procedure may be safely substituted for IFN in selected women with early-stage vulvar cancer.
Primary carcinoma of the vulva is a rare but debilitating disease of primarily elderly women. In the last 100 years, surgical excision following the Halsteadian approach for breast cancer led to disease cures, but with great morbidity and disfiguration. Significant milestones in contemporary management came with documentation of: 1) the safety of separating the primary radical excision of the vulva from the IFN (the "triple incision" technique),1 2) the recognition that lateralized primary tumors were rarely associated with bilateral groin metastases,2 and 3) primary vulvar excision didn't require complete vulvectomy. Further advances came with introduction of radiation (and chemoradiation) both as adjuvant and neoadjuvant therapy.3 Indeed, these modifications improved survival, reduced morbidity, and provided, in many cases, functionality to the vulva. SLN biopsy is the next great iteration in this continuum. The importance of the procedure is underscored by the observation that most women with early-stage disease will not have nodal spread and gain nothing other than morbidity, such as lymphedema, from IFN. The obvious concern in adopting a "minimalization" alternative to full IFN is missing prevalent disease without therapy,4 particularly since recurrent groin disease is particularly difficult to manage and is often a fatal event.
SLN biopsy is not new to management of vulvar cancer; early descriptions appeared in the early 1990s.5 However, large-scale validation took the international community to assemble the collective experience of two organizations to highlight the safety of this approach. I have previously highlighted one of these, the GROINS-V study, which reported about 4 years ago.6 The latest, from the Gynecologic Oncology Group, largely recapitulates that experience, particularly when similar cohorts are examined. The primary difference between the studies, though, is the level of experience of the contributing members. The majority of contributors to the latter study were novices with the technique and did not have to undergo a competency evaluation prior to participating in the trial. This may have led to the higher than initially expected false-negative rate, but it provides external validity for the procedure in this rare disease. Under the identified constraints (tumors less than 4 cm, squamous histology, and clinically negative groins), SLN appears to be safely substituted for IFN. Current investigation is prospectively assessing the merit of SLN-only groin dissection (node negative and node positive) for survival and morbidity, including quality of life.
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