Sentinel lymph node detection in early stage uterine cervix carcinoma: A systematic review

doi:10.1016/j.ygyno.2007.05.010

Gynecologic Oncology

Volume 106, Issue 3, September 2007, Pages 604-613

https://doi.org/10.1016/j.ygyno.2007.05.010 Get rights and content

Abstract

Objective.

The aim of this study was to systematically review the diagnostic performance of Sentinel Node (SN) detection for assessing the nodal status in early stage cervical carcinoma, and to determine which technique (using blue dye, Technetium-99m colloid (^99mTc), or the combined method) had the highest success rate in terms of detection rate and sensitivity.

Methods.

A comprehensive computer literature search of English language studies in human subjects on Sentinel Node procedures was performed in MEDLINE and EMBASE databases up to July 2006. For each article two reviewers independently performed a methodological qualitative analysis and data extraction using a standard form. Pooled values of the SN detection rate and pooled sensitivity values of the SN procedure are presented with a 95% confidence interval (95% CI) for the three different SN detection techniques.

Results.

We identified 98 articles, and 23 met the inclusion criteria, comprising a total of 842 patients. Ultimately, 12 studies used the combined technique with a sensitivity of 92% (95% CI: 84–98%). Five studies used ^99mTc-colloid, with a pooled sensitivity of 92% (95% CI: 79–98%; p = 0.71 vs. combined technique), and four used blue dye with a pooled sensitivity of 81% (67–92%, p = 0.17 vs. combined technique).

The SN detection rate was highest for the combined technique: 97% (95% CI: 95–98%), vs. 84% for blue dye (95% CI: 79–89%; p < 0.0001), and 88% (95% CI: 82–92%, p = 0.0018) for ^99mTc colloid.

Conclusion.

SN biopsy has the highest SN detection rate when ^99mTc is used in combination with blue dye (97%), and a sensitivity of 92%. Hence, according to the present evidence in literature the combination of ^99mTc and a blue dye for SN biopsy in patients with early stage cervical cancer is a reliable method to detect lymph node metastases in early stage cervical cancer.

Introduction

Uterine cervical cancer remains the third most common female malignancy worldwide, despite a gradual fall in its frequency in western countries [1]. This disease continues to be diagnosed in locally advanced stages despite screening in many countries. In western countries, half of patients are detected through symptoms such as abnormal vaginal bleeding and vaginal discharge, and the remaining ones by screening [2]. The Federation Internationale de Gynecologie et d'Obstetrique (FIGO) clinical staging system does not include evaluation of lymph node involvement. However, lymph node status remains the single most important prognostic factor in early stage cervical cancer [3], [4], [5], [6].

Systematic lymph adenectomy is the standard technique currently used to detect lymphatic spread. Lymph node involvement is common, up to 27% in early stages [7], [8], [9], [10], [11], [12], [13], [14].

For patients with early stage cervical cancer in the Western world, radical hysterectomy and pelvic lymph node dissection are the treatment of choice [15]. In the event of proven lymphatic metastases, (chemo) radiation is the primary treatment [16].

Approximately up to 25% of operable cases will eventually require additional chemo-radiation therapy [8]. Patients with proven microscopic lymph node metastases derive no benefit from lymph adenectomy in invasive cervical cancer, so complete pelvic lymph node dissection seems unnecessary for some cases when radiotherapy is offered [10], [17], [18], [19], [20], [21].

In the search of more accurate preoperative diagnostics, cross-sectional imaging modalities such as computed tomography and magnetic resonance imaging have been proposed [22]. Unfortunately, all these imaging techniques notoriously fail to reliably detect lymph node metastases [23].

Since the introduction by Cabanas of the sentinel node concept to reduce the complication rate of lymphadenectomy, it has been proven feasible to detect lymph node metastasis on the basis of selective lymph node dissection [24]. When nodal metastases occur, the sentinel lymph node will be initially involved. According to the sentinel node hypothesis, histologically tumor negative sentinel lymph nodes predict that also the remaining lymph nodes will be free of tumor [25], [26]. This hypothesis has proven to be true in melanoma and breast cancer and is currently being studied in the treatment of other malignancies, such as cervical and vulvar cancer [12], [27], [28], [29], [30].

The aim of this systematic review is to summarize the available evidence on the sensitivity of the sentinel node biopsy in cervical cancer, and to explore whether its feasibility is a function of the SN localizing technique.

Section snippets

Data sources and study selection

A comprehensive computer literature search of English language studies in human subjects was performed to identify articles on the diagnostic performance of SN and cervical carcinoma compared with histopathology as reference standard.

The MEDLINE and EMBASE databases to July 2006 were searched for the following terms: “cervix neoplasm, sentinel node” as medical subject headings (MeSH) and “specificity/or false negative/or accuracy” as text words. The list of articles was supplemented by

Literature search

The search strategy yielded 62 publications in EMBASE and 56 in MEDLINE; 22 studies were identified in both databases. From the resulting 78 studies, 35 were excluded after reviewing the information provided in the title and abstract. Reviewing the full articles of the 43 remaining studies resulted in exclusion of another 18 studies because of ineligibility [17] and duplicate publication [1], [33]. For the meta-analysis of the sensitivity, we excluded two studies due to absence of data

Methodological qualitative analysis

There were 22 prospective studies. Inclusion criteria were described in 13 studies, and exclusion criteria in 9 studies. Sixteen studies included a consecutive patient population (see also Table 2). The amount of injected blue dye varied from 0.2 ml [54] to 4 ml (Table 3). The amount of activity (in MBq) of ^99mTc varied from 10–20 MBq [48] to 228 MBq [47]. In all studies using a radioactive tracer a preoperative scintigraphy was performed. In 14/19 studies, the 4-quadrant method was used. All

Quantitative analysis (meta-analysis)

The sensitivity to detect lymph node metastases for all studies (two were excluded, n = 21) was 89% (95% CI: 83–94%), with only a limited heterogeneity (chi-square 29.7, degrees of freedom (df) = 20, p = 0.075). Subgroup analysis for the three detection techniques revealed a homogeneous distribution if ^99mTc only or the combined detection technique was used (chi-squared 9.2, df = 11, p = 0.60 for ^99mTc colloid and blue dye and chi-square 5.3, df = 4, p = 0.26 for ^99mTc alone). The results of the studies

Discussion

The aim of this systematic review is to summarize the available evidence for and to obtain valid and precise summary estimates of the diagnostic performance of the (laparoscopic) sentinel node technique for detecting lymph node metastasis in early cervical cancer.

The combined technique of ^99mTc and blue dye yields the best results, with a pooled sensitivity of 92% and the highest SN detection rate of 97%. Technetium (^99mTc) alone has a similar sensitivity of 92% but a 9% lower SN detection rate

Acknowledgments

We thank Ingrid I. Riphagen, M.Sc., medical information specialist at the VU University Library, for the aid in defining a search strategy, identifying references and editing the manuscript.