ReviewSentinel lymph node detection in early stage uterine cervix carcinoma: A systematic review
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.
References (61)
- et al.
New technologies in cervical cytology screening: a word of caution
Obstet. Gynecol.
(1999 (Aug)) - et al.
Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy
Gynecol. Oncol.
(1996 (Jul)) - et al.
Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study
Gynecol. Oncol.
(1990 (Sep)) - et al.
Lymph node mapping and sentinel node detection in patients with cervical carcinoma: a 2-year experience
Gynecol. Oncol.
(2005 (Dec)) - et al.
Value of intraoperative imprint cytology of sentinel nodes in patients with cervical cancer
Gynecol. Oncol.
(2004 (Jul)) - et al.
A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group Study
Gynecol. Oncol.
(1989 (Dec)) - et al.
Randomised study of radical surgery versus radiotherapy for stage Ib–IIa cervical cancer
Lancet
(1997 (Aug 23)) - et al.
Modified radical hysterectomy in the treatment of early squamous cervical cancer
Gynecol. Oncol.
(1999 (Feb)) - et al.
Lymphatic spread in stage Ib and II cervical carcinoma: anatomy and surgical implications
Obstet. Gynecol.
(1998 (Mar)) - et al.
Early invasive cervical cancer with pelvic lymph node involvement: to complete or not to complete radical hysterectomy?
Gynecol. Oncol.
(1990 (Apr))