Prognostic significance of low volume sentinel lymph node disease in early-stage 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
References (24)
- et al.
Sentinel lymph node identification (SNI) in the management of conservative surgery in early cervical cancer: is it acceptable?
Gynecol Oncol
(2005) - et al.
The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm
Gynecol Oncol
(2010) - et al.
Topographic distribution of sentinel lymph nodes in patients with cervical cancer
Gynecol Oncol
(2006) - et al.
Sentinel node (SLN) biopsy in the management of locally advanced cervical cancer
Gynecol Oncol
(2009) - et al.
Sentinel lymph node biopsy in gynaecological cancers: the importance of micrometastasis in cervical cancer
Surg Oncol
(2008) - et al.
The number of positive nodes and the ratio of positive to excised nodes are significant predictors of survival in women with micrometastatic node-positive breast cancer
Eur J Cancer
(2008) - et al.
Detection of pelvic lymph node micrometastasis in stage IA2-IB2 cervical cancer by immunohistochemical analysis
Gynecol Oncol
(2004) - et al.
Clinical significance of lympho vascular space involvement and lymph node micrometastasis in early-stage cervical cancer: a retrospective case-control surgico-pathological study
Gynecol Oncol
(2005) - et al.
Detection of micrometastasis in pelvic lymph nodes in patients with carcinoma of the cervix uteri using step sectioning: frequency, topographic distribution and prognostic impact
Gynecol Oncol
(2008) - et al.
Sentinel node identification in cervical cancer patients undergoing transperitoneal radical hysterectomy: a study of 100 cases
Int J Gynecol Cancer
(2006)
Multicenter validation study of the sentinel lymph node concept in cervical cancer: AGO Study Group
J Clin Oncol
Sentinel lymph node biopsy as guidance for radical trachelectomy in young patients with early stage cervical cancer
BMC Cancer
Cited by (171)
Value of routine cytokeratin immunohistochemistry in detecting low volume disease in cervical cancer
2022, Gynecologic OncologyCitation Excerpt :Evidence on the impact of low volume disease on survival of patients is limited and controversial, due to the low incidence of both low volume disease in SLNs and recurrence [3,7,8]. To date, clinical evidence indicates that the presence of isolated tumor cells (ITC) in SLNs is not prognostically associated with reduced survival [1,7,9,10]. Therefore, finding ITC does not necessarily impact therapeutic strategy whereas finding micrometastases does and usually adjuvant chemoradiation will be given [11].
“Long-term outcome in endometrial cancer patients after robot-assisted laparoscopic surgery with sentinel lymph node mapping”
2022, European Journal of Obstetrics and Gynecology and Reproductive Biology
- ☆
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.