Abstract and Introduction
Abstract
In early-stage cervical cancer, lymph node status is of paramount importance to determine the best therapeutic strategy and is one of the most important prognostic factors of survival. According to main international guidelines, pelvic full lymphadenectomy is recommended for lymph node staging. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement and has been suggested instead of systematic pelvic lymph node dissection (PLND). The SLN technique requires a learning-curve to be well performed. Combined detection with technetium-99 and blue dye has been widely used but the recent introduction of indocyanine green (ICG) is of growing interest since it could improve SLN detection. SLN biopsy offers a more accurate anatomical staging by finding potential metastatic nodes outside of usual lymphadenectomy areas. SLN biopsy improves the diagnostic value of lymph node staging with ultrastaging and detection of low-volume nodal metastases [isolated tumor cells (ITCs) and micrometastases]. Appropriate selection of patient and minimal training combined with some simple rules may guarantee a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-limb lymphoedema, which severely affects patient quality of life. Some points are still subject to debate such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognosis. Although international guidelines consider SLN biopsy as an alternative to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence on long-term oncological safety. The 3 ongoing prospective trials SENTIX, PHENIX and SENTICOL III will most probably give an answer to these issues.
Introduction
With nearly 570,000 new cases/year and 310,000 deaths/year, cervical cancer is the second most frequent cancer in women and the third leading cause of cancer-related deaths in females.[1] The incidence and the mortality are a matter of concern in developing countries where screening programs are not always available. Additional measures such as patient education, changes in sexual behaviour and the introduction of HPV-vaccination may decrease the impact of this cancer.[2,3] It is important to emphasize that more than 54% of patients diagnosed are younger than 50 years.[4]
Based on the prospective data of SENTICOL I and LACC trial, good oncologic outcomes after surgery have been reported for early-stage cervical cancer with a disease-free survival of 90.6% at 3 years and 96.5% at 4.5 years respectively and an overall survival of 96% and 99%, respectively.[5,6] For this subset of patients, lymph node status is a major prognostic factor since five-year disease-free survival falls from 88% to 57% in case of lymph node metastasis[7] and has been recently included in the 2018 current International Federation of Gynecology and Obstetrics (FIGO) classification.[8] Moreover, lymph node assessment is of paramount importance to determine the most appropriate therapeutic strategy for patients with early-stage cervical cancer, since positive pelvic node may require para-aortic lymphadenectomy and chemoradiotherapy rather than radical surgery.
According to main international guidelines, full pelvic lymphadenectomy is recommended for lymph node staging.[9,10] Nevertheless, this surgical procedure is associated with significant morbidity, especially a higher risk of lower limbs lymphedema.[11,12] The current trend in cervical cancer management is focused on less aggressive strategy without jeopardizing oncologic outcomes. Introduced first in breast cancer[13] and vulvar cancer,[14] the sentinel lymph node (SLN) technique has been applied to early-stage cervical cancer within this logic and several publications have demonstrated the concept, the feasibility and the reliability in this indication.[15–20] Based on European and American guidelines, SLN biopsy without additional lymphadenectomy is considered as acceptable for 2018 FIGO IA1 with lymphovascular space invasion (LVSI) and IA2 stages.[9,10] On the other hand, SLN biopsy alone is not recommended without systematic pelvic lymphadenectomy for lymph node staging for IB1 stage except in the context of prospective clinical trials according to the ESGO/ESTRO/ESP guidelines[9] whereas SLN biopsy could be considered for these cases according to the 2019 NCCN guidelines.[10]
In this article, we review the current evidence on SLN biopsy concept in cervical cancer to determine whether SLN biopsy might be the gold-standard for lymph node staging.