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Cervical cancer (CC) is the fourth most common neoplasia in women worldwide. Although early-stage CC is often curable, 40 to 50% of patients are diagnosed at a locally advanced stage. Metastatic disease accounts for the principal cause of death. Lymph node (LN) status is a major factor impacting treatment options and prognosis. Historically, CC was staged based only on clinical findings. However, in 2018, imaging modalities and/or pathological findings were included in the International Federation of Gynecology and Obstetrics (FIGO) staging classification. In the last decades, LN status assessment has evolved considerably. Full pelvic lymphadenectomy used to be the only way to determine LN status. Currently, several options exist: surgery with full lymphadenectomy, sentinel lymph node (SLN) biopsy or imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Regarding surgery, the SLN biopsy technique has become a standard procedure in cases of CC, with indocyanine green (ICG) being the preferred dye. Pelvic MRI is a valuable imaging technique modality for the evaluation of pelvic LNs. In locally advanced or in early-stage disease with suspicious LNs on CT scans or MRI, PET/CT is recommended for assessment of nodal and distant status. The best strategy for LN assessment remains a highly controversial topic in the literature. In this article, we aim to review and compare the advantages and limitations of each modality, i.e. imaging or surgical (lymphadenectomy or SLN biopsy) approaches. [ABSTRACT FROM AUTHOR]

Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on PET/CT while others recommend to rely on surgical staging. We report the rate of patients for whom the radiation field defined on PET/CT was modified by the histological PALN status. Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiotherapy (EBRT) field defined on the PET/CT basis. Of 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastases. Of 17 patients with positive PALNs on PET/CT, 9 were negative on histology of which 7 were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT - field adaptation (pelvic vs extended field). The rate of radiation field modification (27,7%) was particularly high in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT. Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLNs at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive LNs in the common iliac region. [ABSTRACT FROM AUTHOR]

Objectives FIGO classification is commonly used for staging of locally advanced cervical cancer. Laparoscopic para-aortic lymphadenectomy is currently used as a diagnostic tool, since we know that presence of para-aortic lymph node metastases identifies patients with poor prognosis. The application of robotics during this procedure needs to be investigated. Design Retrospective multi-center study. Setting Three centers participated in building one database. Population Thirty-seven patients with locally advanced cervical cancer underwent a robot-assisted laparoscopic para-aortic lymphadenectomy. Methods Patients were prospectively enrolled in one register. Retrospective analysis of the whole database was performed. Main outcome measures Surgical outcomes of the robot-assisted procedure and follow-up data. Results Median number of lymph nodes collected was 27.5 (1-54) per patient. Five of 37 patients had para-aortic node metastases. The false negative rate for PET- CT diagnosing para-aortic node metastases was 11.4% (4/35). Two major intra-operative complications occurred (5.4%). Postoperative morbidity was low (13.5%). Median follow-up was 27 months [95% confidence interval (95% CI) was 24-30]. Median disease-free survival was 16 months (95% CI 2.4-29.6). Patients with negative nodes had a median disease-free survival of 24 months (not assessable), although patients with positive nodes had a median disease-free survival of 9 months (95% CI 6.9-11.9). Conclusions In this series we report that robot-assisted laparoscopic para-aortic lymphadencetomy provided the surgeon with useful information, diagnosing 11.4% of occult para-aortic lymph node metastases in women with locally advanced cervical cancer. Intra-operative and postoperative morbidity were low. The presence of para-aortic lymph node metastases correlated with shorter disease-free survival. [ABSTRACT FROM AUTHOR]

The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms. An original digital image analysis methodology was used to objectively determine whole slide densities and spatial distributions of immunostained structures. We observed a marked increase in lymphatic vessel density (LVD) and a specific capsular and subcapsular distribution in pre-metastatic SLN when compared with non-sentinel counterparts. Such features persisted in the presence of nodal metastatic colonization. The inflammatory profile attested by CD8+, Foxp3, CD20 and PD-1expression was also significantly increased in pre-metastatic SLN. Remarkably, the densities of CD20+B cells and PD-1 expressing germinal centers were positively correlated with LVD. All together, these data strongly support the existence of a pre-metastatic dialog between the primary tumor and the first nodal relay. Both lymphatic and immune responses contribute to the elaboration of a specific pre-metastatic microenvironment in human SLN. Moreover, this work provides evidence that, in the context of early cervical cancer, a pre-metastatic lymphangiogenesis occurs within the SLN (pre-metastatic niche) and is associated with a specific humoral immune response. [ABSTRACT FROM AUTHOR]