Incidence of Histologically Proven Pelvic and Para-Aortic Lymph Node Metastases and Rate of Upstaging in Patients with Locally Advanced Cervical Cancer: Results of a Prospective Randomized Trial

Tsunoda, Audrey Tieko; Marnitz, Simone; Nunes, João; Andrade, Carlos Eduardo Mattos da Cunha; Neto, Christovam Scapulatempo; Blohmer, Jens-Uwe; Herrmann, Jörg; Kerr, Lígia Maria; Martus, Peter; Schneider, Achim; Favero, Giovanni; Köhler, Christian

doi:10.1159/000453666

Cited by 33 publications

(22 citation statements)

References 55 publications

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“…Cervical cancer is one of the common malignancies in females worldwide (1). In recent years, the cervical cancer screening technique has been improved and popularized in developed areas (1).…”

Section: Discussionmentioning

confidence: 99%

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miR‑146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6

Tian

et al. 2019

Oncol Rep

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The aim of the present study was to investigate whether miRNA-146a regulated the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis. miR-146a expression was increased in human cervical cancer. Both overall survival (OS) and disease-free survival (DFS) of low miR-146a expression were higher than those of high miR-146a expression. Additionally, IL-17a expression was lower in patients with high miR-146a expression compared to that of patients with lower miR-146a expression. In a co-culture of cervical cancer and CD4 + T cells, downregulation of miR-146a inhibited cell growth and induced apoptosis of cervical cancer cells, while overexpression of miR-146a promoted cell growth and reduced apoptosis of cervical cancer cells. Downregulation of miR-146a induced TRAF6 and NF-κB protein expression, increased IL-6, IL-17A and IL-21 levels, and enhanced p-STAT3 protein expression. The inhibition of TRAF6 attenuated the effects of anti-miR-146a on the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis. Collectively, miR-146a regulated the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF-κB signaling by targeting TRAF6. miR-146a may function as an oncogene in cervical cancer via Th17 cell differentiation by targeting TRAF6.

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Section: Discussionmentioning

confidence: 99%

“…Cervical cancer is one of the most common gynecological malignancies. Its morbidity is ranked in the third place among global female malignancies (1). Furthermore, it is ranked in the second place in developing countries in terms of both morbidity and mortality, only second to breast cancer.…”

Section: Introductionmentioning

confidence: 99%

miR‑146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6

Tian

et al. 2019

Oncol Rep

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“…Original research involvement occurs in approximately 10-50% of patients with locally advanced cervical cancer. [1][2][3] Known limitations of imaging modalities, even positron emission tomography-computed tomography (PET-CT), lead to false negative rates of 8-20%, [4][5][6] potentially advocating surgical staging. However, this has been a controversial topic among gynecologic oncologists and radiation oncologists for decades due to contradictory results published in the literature.…”

Section: Highlightsmentioning

confidence: 99%

Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB–IVA: oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study

Marnitz

Tsunoda

Martus

et al. 2020

Int J Gynecol Cancer

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ObjectiveRevised staging of patients with locally advanced cervical cancer is based on clinical examination, imaging, and potential surgical findings. A known limitation of imaging techniques is an appreciable rate of understaging. In contrast, surgical staging may provide more accurate information on lymph node involvement. The aim of this prospective study was to evaluate the impact of pre-treatment surgical staging, including removal of bulky lymph nodes, on disease-free survival in patients with locally advanced cervical cancer.MethodsUterus-11 was a prospective international multicenter study including patients with locally advanced cervical cancer who were randomized 1:1 to surgical staging (experimental arm) or clinical staging (control arm) followed by primary platinum-based chemoradiation. Patients with histologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIB–IVA underwent gynecologic examination and pre-treatment imaging including abdominal computed tomography (CT) and/or abdominal magnetic resonance imaging (MRI). Patients had chest imaging (any of the following: X-ray, CT, or PET-CT). The primary endpoint was disease-free survival and the secondary endpoint was overall survival. An ad hoc analysis was performed after trial completion for cancer-specific survival. Randomization was conducted from February 2009 to August 2013.ResultsA total of 255 patients (surgical arm, n=130; clinical arm, n=125) with locally advanced cervical cancer were randomized. Of these, 240 patients were eligible for analysis. The two groups were comparable with respect to patient characteristics. The surgical approach was transperitoneal laparoscopy in most patients (96.6%). Laparoscopic staging led to upstaging in 39 of 120 (33%) patients. After a median follow-up of 90 months (range 1–123) in both arms, there was no difference in disease-free survival between the groups (p=0.084). For patients with FIGO stage IIB, surgical staging is superior to clinical staging with respect to disease-free survival (HR 0.51, 95% CI 0.30 to 0.86, p=0.011). In the post-hoc analysis, surgical staging was associated with better cancer-specific survival (HR 0.61, 95% CI 0.40 to 0.93, p=0.020).ConclusionOur study did not show a difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer. There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging. The high risk of distant metastases in both arms emphasizes the need for further evaluation.

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“…Thus, negative imaging findings for lymph node metastases based on any imaging modality do not rule out occult lymph node metastases in cervical cancer. This is clearly illustrated by a recent randomized trial reporting significant rate of upstaging (33%) after surgical staging (including paraaortic lymph node dissection) compared to clinical/radiological stage, in locally advanced cervical cancer patients (FIGO stage 2B-4) [15]. These limitations in diagnosing paraaortic lymph node metastases preoperatively are also taken into account in the ESGO-ESTRO-ESP cervical cancer guidelines (2018), which recommend surgical staging, consisting of paraaortic lymph node dissection in locally advanced cervical cancer also in patients with negative paraaortic lymph nodes on imaging [11].…”

Section: Diagnostic Imaging At Primary Stagingmentioning

confidence: 99%

What Is the Role of Imaging at Primary Diagnostic Work-Up in Uterine Cervical Cancer?

et al. 2019

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Purpose of Review For uterine cervical cancer, the recently revised International Federation of Gynecology and Obstetrics (FIGO) staging system (2018) incorporates imaging and pathology assessments in its staging. In this review we summarize the reported staging performances of conventional and novel imaging methods and provide an overview of promising novel imaging methods relevant for cervical cancer patient care. Recent Findings Diagnostic imaging during the primary diagnostic work-up is recommended to better assess tumor extent and metastatic disease and is now reflected in the 2018 FIGO stages 3C1 and 3C2 (positive pelvic and/or paraaortic lymph nodes). For pretreatment local staging, imaging by transvaginal or transrectal ultrasound (TVS, TRS) and/or magnetic resonance imaging (MRI) is instrumental to define pelvic tumor extent, including a more accurate assessment of tumor size, stromal invasion depth, and parametrial invasion. In locally advanced cervical cancer, positron emission tomography-computed tomography (PET-CT) or computed tomography (CT) is recommended, since the identification of metastatic lymph nodes and distant metastases has therapeutic consequences. Furthermore, novel imaging techniques offer visualization of microstructural and functional tumor characteristics, reportedly linked to clinical phenotype, thus with a potential for further improving risk stratification and individualization of treatment. Summary Diagnostic imaging by MRI/TVS/TRS and PET-CT/CT is instrumental for pretreatment staging in uterine cervical cancer and guides optimal treatment strategy. Novel imaging techniques may also provide functional biomarkers with potential relevance for developing more targeted treatment strategies in cervical cancer.

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Incidence of Histologically Proven Pelvic and Para-Aortic Lymph Node Metastases and Rate of Upstaging in Patients with Locally Advanced Cervical Cancer: Results of a Prospective Randomized Trial

Cited by 33 publications

References 55 publications

miR‑146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6

miR‑146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6

Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB–IVA: oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study

What Is the Role of Imaging at Primary Diagnostic Work-Up in Uterine Cervical Cancer?

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