Elsevier

Gynecologic Oncology

Volume 124, Issue 3, March 2012, Pages 496-501
Gynecologic Oncology

Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer

https://doi.org/10.1016/j.ygyno.2011.11.037Get rights and content

Abstract

Objective

Evaluate prognostic significance of low volume disease detected in sentinel nodes (SN) of patients with early stages cervical cancer. Although pathologic ultrastaging of SN allows for identification of low volume disease, including micro-metastasis and isolated tumor cells (ITC), in up to 15% of cases, prognostic significance of these findings is unknown.

Methods

A total of 645 records from 8 centers were retrospectively reviewed. Enrolled in our study were patients with early-stage cervical cancer who had undergone surgical treatment including SN biopsy followed by pelvic lymphadenectomy and pathologic ultrastaging of SN.

Results

Macrometastasis, micrometastasis, and ITC were detected by SN ultrastaging in 14.7%, 10.1%, and 4.5% patients respectively. False negativity of SN ultrastaging reached 2.8%. The presence of ITC was not associated with significant risk, both for recurrence free survival and overall survival. Overall survival was significantly reduced in patients with macrometastasis and micrometastasis; hazard ratio for overall survival reached 6.85 (95% CI, 2.59–18.05) and 6.86 (95% CI, 2.09–22.61) respectively. Presence of micrometastasis was an independent prognostic factor for overall survival in a multivariable model.

Conclusion

Presence of micrometastasis in SN in patients with early stage cervical cancer was associated with significant reduction of overall survival, which was equivalent to patients with macrometastasis. No prognostic significance was found for ITC. These data highlight the importance of SN biopsy and pathologic ultrastaging for the management of cervical cancer.

Highlights

► Presence of micrometastasis in sentinel lymph nodes in patients with early stage cervical cancer is associated with significant reduction of overall survival. ► Prognostic significance of micrometastasis in sentinel node for overall survival is equivalent to macrometastasis. ► Presence of isolated tumor cells (ITC) in sentinel node is not associated with significant risk for survival.

Introduction

Sentinel node (SN) biopsy is increasingly used in the management of cervical cancer [1], [2], [3], [4]. It may improve the accuracy of staging by identification of lymph nodes in atypical localizations, which can therefore be missed during systematic pelvic lymphadenectomy [2], [5]. It is used for triaging the patients toward surgery or radiotherapy [6], and selecting candidates for fertility sparing treatment [7], [8], [9]. Several prospective randomized studies are ongoing, the aims of which are to determine the oncologic safety of avoiding systematic pelvic lymphadenectomy in patients without involvement of the SN.

Identification of 2 to 4 sentinel nodes allows for their extensive processing by pathologic ultrastaging (multiple serial sectioning with immunohistochemical assessment). Pathologic ultrastaging increases detection rate of low volume disease, which includes micrometastasis and isolated tumor cells (ITC) [10]. In patients with FIGO stages IA2-IIB cervical cancer, micrometastasis are being detected in SN of 4%–15% of patients [11], [12]. However, significance of low volume disease for prognosis of the disease has not been established, and therefore its implication for adjuvant treatment is not known.

The aim of our multicenter retrospective cohort study was to collect data from gynecologic oncology centers that perform SN biopsy and pathologic ultrastaging in cervical cancer patients, and to use these data to determine the significance of micrometastasis and isolated tumor cells for the disease prognosis.

Section snippets

Patients and therapeutic procedures

Enrolled were patients with early-stage cervical cancer (FIGO stages IA–IIB) in whom surgical treatment was performed, including SN biopsy followed by systematic pelvic lymphadenectomy. Only patients with histologically confirmed squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, in whom SN were processed by the ultrastaging protocol, and data on the follow-up were available, were included. A total of 645 records from 8 centers (Ostrava (195), Prague (119), Amsterdam/Utrecht (115),

Statistical methods

Standard summary statistics were used to describe data. ML-χ2 test was applied to assess mutual associations between binary or categorical variables in contingency tables or to measure trend changes in frequency tables over categories of ordinal stratifying factor. The diagnostic power of age as a potential predictor was assessed on the basis of Receiver Operating Characteristics (ROC) curves. The ROC analysis was performed using the ROC web calculator [14] for curve fitting, SPSS 17.02 [15]

Initial description of sample data set

Basic group characteristics are summarized in Table 1. Majority of the sample is formed by Stage I tumors (stage I: 91.5%) of squamous histology (71.3%). Median follow-up for the whole group reached 40 months. The spectrum of patients was heterogeneous in age (range, 23 to 93 years); therefore, all analyses that focused on overall survival endpoints were controlled for the influence of age as background prognostic risk factor.

Macrometastasis, micrometastasis, and isolated tumor cells were

Discussion

A large cohort of 645 patients with early-stage cervical cancer who underwent surgical treatment including SN biopsy and microstaging allowed for the analysis of prognostic significance of detected micrometastasis and ITC. The presence of micrometastasis was associated with significantly reduced overall survival, which corresponded to the patients with macrometastasis, while no increased risk was associated with the detection of ITC.

Prevalence of micrometastasis in SN from patients with

Funding

This work was not supported by any grant.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

The authors thank Rene Verheijen and Ronald Zweemer (University Medical Center Utrecht, Utrecht, The Netherlands), Grzegorz Dyduch and Pawel Basta (Jagellonian University Medical College, Krakow, Poland), Peter Graf and Jaroslav Klat (University Hospital Ostrava, Czech), Jan Lacheta (General University Hospital in Prague, Czech), Chris Meijer (VU Academic Medical Center, Amsterdam, The Netherlands), Eliane Mery and Anne-Claire Sans (Institute Claudius Regaud, Toulouse, France), Fabrice Lecuru

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    The study has not been sponsored or supported by any source. No funding has been received from National Institutes of Health (NIH); Welcome Trust; Howard Hughes Medical Institute (HHMI); or other similar organizations.

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