FIGO Stage IB Research Articles

Simple trachelectomy following neoadjuvant chemotherapy in cervical cancer over 2 cm in size: A case report and review of literature

In the past few decades fertility preservation has emerged as a treatment modality for cervical cancer patients. Different surgical methods have been described, such as open or minimally invasive trachelectomy and gross cervical conisation combined with laparoscopic lymphadenectomy. A thirty-year-old nulliparous woman with uterine cervical cancer FIGO stage IB2 (classification from 2009) underwent neoadjuvant chemotherapy. After three cycles of chemotherapy with cisplatin and iphosphamide there was no colposcopic findings of cervical invasion, therefore a conservative surgery was performed. The patient underwent laparoscopic pelvic lymphadenectomy, cervical amputation and the endocervical curettage. The histopathology confirmed a complete response to chemotherapy.

Acceleration of cervical cancer diagnosis with human papillomavirus testing below age 30: Observational study.

Several international cervical screening guidelines advise against using high-risk human papillomavirus (HR-HPV) testing in women younger than 30. The rationale for this in young women, lies in the potential for additional detection of both low-grade and high-grade cervical intraepithelial neoplasia (CIN) leading to unnecessary treatments without reducing the burden of cervical cancer. We studied 56 544 women screened at 24 to 29 with HR-HPV testing and 116 858 screened with liquid-based cytology (LBC) in the English HPV screening pilot. They were compared to 528 460 women screened at the age of 30 to 49. We studied the detection of cervical cancer and CIN2/3 across two consecutive screening rounds 3 years apart. At 24 to 29, a positive HR-HPV test detected more cases of cervical cancer in the prevalence round than did a positive LBC test (1.36/1000 screened vs 0.82/1000, ORadj : 1.61, 95% CI: 1.18-2.19). In women with a negative HR-HPV test, cervical cancer was diagnosed before or at the incidence round in 0.07/1000. After a negative LBC test, cancer detection reached 0.47/1000 and 40% of these cases were diagnosed at FIGO stage IB+. HR-HPV testing increased the detection of CIN2/3 diagnoses in two consecutive rounds combined by 30% (71.9/1000 vs 55.2/1000). The patterns of detection of cervical cancer and CIN2/3 were almost identical at older ages. These data support using HR-HPV testing for screening of women younger than 30, which not only accelerates the diagnosis of cervical cancer but leads to a similar relative increase in CIN2/3 diagnosis to that found in women aged 30 to 49.

Cervical conization before primary radical hysterectomy has a protective effect on disease recurrence in early cervical cancer: A two-center matched cohort study according to surgical approach

ObjectiveTo ascertain whether cervical conization before radical hysterectomy (RH) has a protective effect on survival outcomes in early cervical cancer, taking into account the surgical approach. MethodsFrom cervical cancer cohorts of two institutions, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH between July 2006 and June 2020. Patients were divided into conization group (n = 144) and control group (n = 434). We conducted three independent 1:1 propensity score matching processes for histology, lymphovascular space invasion, cervical tumor size, and surgical approach (all patients, those who underwent open surgery, and those who underwent minimally invasive surgery [MIS]). Survival outcomes were compared. ResultsOverall, the conization group had less cervical tumor size and received MIS more frequently (P = 0.010) and adjuvant treatment less often (P = 0.002) versus the controls. After matching, the conization group showed significantly better disease-free survival (DFS) versus control (3-year DFS rate, 94.2% vs. 86.3%; P = 0.012), but similar overall survival. Among the open RH matched patients (n = 96), no difference in DFS was observed between the conization and control groups (P = 0.984). In contrast, among the MIS RH matched patients (n = 192), the conization group showed significantly better DFS versus control (3-year DFS rate, 95.7% vs. 82.9%; P = 0.005). In multivariate analysis adjusting for cervical tumor size and adjuvant treatment, conization was identified as an independent favorable prognostic factor for DFS (adjusted HR, 0.318; 95% CI, 0.134–0.754; P = 0.009). ConclusionsPreoperative cervical conization might reduce the disease recurrence rate in early cervical cancer patients who undergo primary MIS RH.

Are IgG antibodies to heat shock proteins HSP27 and HSP60 useful markers in endometrial cancer and cervical cancer?

Heat shock proteins are overexpressed in many human malignancies. The role of heat shock proteins as a therapeutic target in cancer as well as their association with drug resistance were widely documented. The aim of this study was to evaluate the concentration of IgG class HSP27 and HSP60 antibodies in serum of patients with endometrial and cervical cancer, as well as to analyse the variability of concentrations of the examined antibodies depending on the cancer stage. The study included 59 women with adenocarcinoma of the endometrium and 36 women with cervical cancer, the control group consisted of 54 healthy women. The concentrations of IgG class antibodies against the tested heat shock proteins were determined by an immunoenzymatic assay (ELISA) using commercial assays. In both endometrial and cervical cancer, the serum concentration of IgG anti-HSP27 antibody was significantly higher than in the healthy control group. The concentration of IgG anti-HSP60 antibody in endometrial cancer, cervical cancer and healthy control was similar. The median IgG anti-HSP27 antibody serum concentration of endometrial cancer patients was not correlated with FIGO-stage. In cervical cancer inverse correlation between concentration of this antibody and FIGO stage was observed. The median IgG anti-HSP60 antibody concentration in serum of endometrial cancer patients was lower in FIGO stage I and II compared to FIGO stage IV and in FIGO stage IA compared to FIGO stage IB. Concentrations of examined antibodies correlated positively with each other, both in the group of women with cancer and in the group of healthy women. The strongest correlations were found in the group of patients with endometrial cancer. Concentration of anti-HSP27 antibody could help in detection of cervical and endometrial cancer. We need to look for the cut-off point in large cohort studies. Anti-HSP27 and anti-HSP60 antibodies should be further evaluated for their potential usage as biomarkers in cervical and endometrial cancer as they shown some correlation with stage of disease.

Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy

BackgroundTo determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH).MethodsWe included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group).ResultsA total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139).ConclusionsAdditional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

Interpretable Machine Learning Model Supported by Parallel Ensemble Learning to Predict Local Recurrence for Patients with Cervical Cancer

Local recurrence in patients with cervical cancer after definitive chemoradiation can be difficult to treat. Early prediction of local recurrence and risk adapted treatment strategies can lead to improved outcomes. Previous machine learning models using clinical features to predict local failure for cervical cancer have achieved modest discriminatory power with reported AUCs ranging from 0.73 - 0.80. In this study, we aim to improve upon a previously developed clinical model at our institution by using an interpretable machine learning classifier, Explainable Boosting Machine (EBM), and evaluate the impact of a parallel ensemble design on overall model performance.A retrospective cohort of 95 patients with cervical cancer (FIGO stage IB2 - IVA, no para-aortic involvement) treated with definitive chemoradiation between 2009 - 2016 were included. Patients had a mean age of 48.1 years (range, 26.2 - 78.2 years). Most patients had either FIGO stage IB2 (41%) or IIIB (38%) cervical cancer. After a median follow-up period of 59.7 months (range, 3.5 - 135.3 months), 14 patients experienced a local recurrence and there were 27 deaths. An EBM classifier was trained using the clinical features of age, race, histology, year treated, nodal status at diagnosis, stage, and clinical tumor size at diagnosis. The model was trained and tested using 5-fold cross validation. This process was repeated with 25 independent runs, and the predicted scores for each patient were averaged to determine the ensemble score. The clinical ensemble EBM model was compared to the single iteration EBM model (at the median AUC achieved) in a statistical software with paired samples t-test with ROC analysis function.The ensemble EBM model achieved an AUC of 0.853 ± 0.090 with the clinical features of age, year treated, stage, and clinical tumor size at diagnosis, which was statistically significantly higher than the single iteration EBM model (AUC 0.752 ± 0.090), P = 0.022.Parallel ensemble learning increases the discriminatory power of the proposed interpretable EBM model. The model's performance compares favorably to previous models predicting local failure for cervical cancer using clinical features. This tool could be potentially used to aid clinicians in prognostication for cervical cancer and warrants further evaluation in a separate validation cohort.

Uterine Transposition after Radical Trachelectomy for Fertility Preservation: Step By Step of the Surgical Technique.

<h3>Study Objective</h3> To demonstrate the technique of a laparoscopic uterine transposition for fertility preservation in a patient with a previous radical trachelectomy. <h3>Design</h3> A technical video showing step-by-step a laparoscopic uterine transposition. <h3>Setting</h3> A tertiary referral hospital in Argentina. For surgery, the patient was placed in a dorsal modified lithotomy position. During the pelvic part of the procedure, the surgeon was on the patient's left side, the first assistant on the right, and the second assistant between the patient's legs. When working in the upper abdomen the surgeon moved to the patient's right side, the first assistant was between the patient's legs, and the second assistant to the left side. <h3>Patients or Participants</h3> A 27-year-old woman with a FIGO stage IB1 squamous cell cervical carcinoma who had had a radical trachelectomy, and after histopathological assessment fulfilled the criteria for pelvic external radiation therapy. <h3>Interventions</h3> This intervention for fertility preservation consists of three main steps. During the first one, a minimally invasive surgery is performed to detach the uterus and adnexa from the vagina and to place them in the right upper abdomen, out of the pelvic radiation field. Afterwards, the patient is able to start the radiotherapy without delays, and after finishing it, the last step is to reposition the uterus and adnexa in the pelvis with a laparoscopic approach. <h3>Measurements and Main Results</h3> Two months after surgery, the patient has regular uterine bleeding with oral contraceptives. A transvaginal doppler ultrasound shows normal blood flow to the uterus, and the cervix exhibits a normal appearance on physical examination. <h3>Conclusion</h3> Uterine transposition is a feasible surgery, and it should be considered as an alternative for fertility preservation in women who have a pelvic tumor and require pelvic radiation therapy.

Effectiveness comparisons of various therapies for FIGO stage IB2/IIA2 cervical cancer: a Bayesian network meta-analysis

BackgroundCervical cancer is a common malignancy of the female genital tract. Treatment options for cervical cancer patients diagnosed at FIGO (2009) stage IB2 and IIA2 remains controversial.MethodsWe perform a Bayesian network meta-analysis to directly or indirectly compare various interventions for FIGO (2009) IB2 and IIA2 disease, in order to improve our understand of the optimal treatment strategy for these women. Three databases were searched for articles published between 1971 and 2020. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers.ResultsSeven thousand four hundred eighty-six articles were identified. Thirteen randomized controlled trials of FIGO (2009) IB2 and IIA2 cervical cancer patients were included in the final analysis. These trials used six different interventions: concomitant chemoradiotherapy (CCRT), radical surgery (RS), radical surgery following chemoradiotherapy (CCRT+RS), neoadjuvant chemotherapy followed by radical surgery (NACT+RS), adjuvant radiotherapy followed by Radical surgery (RT + RS), radiotherapy alone (RT).SUCRA ranking of OS and Relapse identified CCRT+RS and CCRT as the best interventions, respectively. Systematic clustering analysis identified the CCRT group as a unique cluster.ConclusionThese data suggest that CCRT may be the best approach for improving the clinical outcome of cervical cancer patients diagnosed at FIGO (2009) stage IB2/IIA2. Phase III randomized trials should be performed in order to robustly assess the relative efficacy of available treatment strategies in this disease context.

Vena cava resection and bypass for recurrent cervical cancer

A 42-year-old woman was diagnosed with a second para-aortic cervical cancer. The patient had undergone a radical hysterectomy with pelvic lymphadenectomy for FIGO stage IB1 squamous cervical cancer 3 years...

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8months (range, 0.49-51.1months). The rate of DFS and OS at 4years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Radiomic Score as a Potential Imaging Biomarker for Predicting Survival in Patients With Cervical Cancer.

ObjectivesAccurate prediction of prognosis will help adjust or optimize the treatment of cervical cancer and benefit the patients. We aimed to investigate the incremental value of radiomics when added to the FIGO stage in predicting overall survival (OS) in patients with cervical cancer.MethodsThis retrospective study included 106 patients with cervical cancer (FIGO stage IB1–IVa) between October 2017 and May 2019. Patients were randomly divided into a training cohort (n = 74) and validation cohort (n = 32). All patients underwent contrast-enhanced computed tomography (CT) prior to treatment. The ITK-SNAP software was used to delineate the region of interest on pre-treatment standard-of-care CT scans. We extracted 792 two-dimensional radiomic features by the Analysis Kit (AK) software. Pearson correlation coefficient analysis and Relief were used to detect the most discriminatory features. The radiomic signature (i.e., Radscore) was constructed via Adaboost with Leave-one-out cross-validation. Prognostic models were built by Cox regression model using Akaike information criterion (AIC) as the stopping rule. A nomogram was established to individually predict the OS of patients. Patients were then stratified into high- and low-risk groups according to the Youden index. Kaplan–Meier curves were used to compare the survival difference between the high- and low-risk groups.ResultsSix textural features were identified, including one gray-level co-occurrence matrix feature and five gray-level run-length matrix features. Only the FIGO stage and Radscore were independent risk factors associated with OS (p < 0.05). The C-index of the FIGO stage in the training and validation cohorts was 0.703 (95% CI: 0.572–0.834) and 0.700 (95% CI: 0.526–0.874), respectively. Correspondingly, the C-index of Radscore was 0.794 (95% CI: 0.707–0.880) and 0.754 (95% CI: 0.623–0.885). The incorporation of the FIGO stage and Radscore achieved better performance, with a C-index of 0.830 (95% CI: 0.738–0.922) and 0.772 (95% CI: 0.615–0.929), respectively. The nomogram based on the FIGO stage and Radscore could individually predict the OS probability with good discrimination and calibration. The high-risk patients had shorter OS compared with the low-risk patients (p < 0.05).ConclusionRadiomics has the potential for noninvasive risk stratification and may improve the prediction of OS in patients with cervical cancer when added to the FIGO stage.

Radical hysterectomy practice patterns for early-stage cervical cancer: a cross-sectional survey of gynecologic oncologists

Objectives: In this study, we evaluated current practice patterns related to radical hysterectomies for early stage cervical cancer and how they have changed since new literature was released in 2018. Methods: This study was a cross-sectional survey of current gynecologic oncologists. The primary outcome assessed was performance of primarily open radical hysterectomies for FIGO Stages IA1, IA2, IB1, and IB2 cervical carcinoma. A secondary outcome assessed was a change in surgical practice. Multivariable logistic regression analyses were completed to assess for associations of demographic and surgical experience predictors. Additional descriptive analyses were performed to evaluate reasons physicians would consider a minimally invasive radical hysterectomy, specific changes made to surgical technique, concerns regarding the 2018 NEJM trials, and beliefs about the role of future clinical trials. Results: Of 1309 SGO members invited to participate, 249 responded (19.0%) and 218 (87.6%) complete responses were analyzed. Performance of primarily open radical hysterectomies was reported in 61.6%, 80.2%, and 88.9% of Stage IA2, IB1, and IB2 cancers, respectively. For Stage IA2 cancer, the age group of 40-49 was associated with 73% lower odds of performing primarily open hysterectomies compared to the reference group of ages 30-39 (OR 0.27, p=0.01). Female gender was associated with greater odds of performing primarily open radical hysterectomies (OR 2.03, p=0.04 for IA2, OR 3.25, p=0.01 for IB1). For Stage IB2 cancers, no demographic or surgical experience factors were statistically associated with performance of open surgery. Change from minimally invasive to open surgery was reported in 52.3%, 68.4%, and 71.1% of Stage IA2, IB1, and IB2 cancers, respectively. Change in minimally invasive technique was reported in 5.5%, 6.42%, and 5.96% of Stage IA2, IB1, and IB2 cancers, respectively. For Stage IA2 cancer, each decrease of 1 year in practice (i.e. since fellowship graduation) was associated with 10% greater odds of changing surgical route or technique. Time since fellowship graduation was associated with 23% greater odds of a change for Stage IB2 cancers. For Stage IB1 cancer, each increase in case volume by 1 radical hysterectomy annually was associated with 6% lower odds of changing surgical route or technique. Most (66.7%) physicians reported they would consider a minimally invasive hysterectomy for one or more reasons. The majority of respondents (84.7%) reported believing there is a role for additional studies evaluating the topic of route of surgery for early stage cervical cancer. Download : Download high-res image (239KB) Download : Download full-size image Conclusions: Despite emerging research demonstrating worse oncologic outcomes for minimally invasive radical hysterectomies in early stage cervical cancer, our research shows that current practices remain heterogeneous. In this study, female surgeons had greater odds of performing open surgery compared to their male colleagues for Stage IA2 and IB1 cancers. The odds for performing open surgery were lower in middle age surgeons compared to younger physicians. More recent fellowship graduation was associated with greater odds of change, indicating that more senior surgeons reported being less likely to change practice. Many individuals reported feeling there is room for additional randomized clinical trials to inform evidence-based practices. Given the high rates of practice change reported, there will also be a role for future epidemiologic studies to evaluate oncologic outcomes in the current practice environment.

Comparative analysis of quality of life for three different adjuvant treatment modality in early stage cervical cancer: an analysis from STARS study

<h3>Objectives:</h3> This analysis aimed to compare the quality of life (QoL) of patients with different adjuvant treatment modalities in STARS study for cervical cancer. <h3>Methods:</h3> QoL assessment was done at the baseline and then longitudinally after completing of radiation or chemotherapy assigned in STARS study. In the study, post-operative FIGO stage IB to IIA cervical cancer patients with adverse pathological factors were randomized in 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation weekly cisplatin or sequential chemoradiation (with cisplatin plus paclitaxel in 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy respectively). QoL was assessed with EORTC QLQ-C30 questionnaires at baseline (1 week after the surgery), during the treatment period (in the 5th week receiving pelvic irradiation), 12 months and 24 months after the completion of treatment. Analysis of variance by one-way repeated measures analyses of variance (ANOVA) was used to compare differences in QoL measures among treatment groups. <h3>Results:</h3> Totally, 816, 633, 360 and 254 patients had completed QoL assessment at baseline, during treatment period, 12 month and 24 month after the completion of treatment. At baseline, a lowest global health status (GH) and functional dimensions including physical, emotional, role, cognitive and social functioning, and lowest scores of symptom and single item scales were presented among the 3 groups with balance (p > 0.05). During treatment period, GH and other functional dimension scores were elevated, with symptom item scores declined in RT group. While in CCRT or SCRT group, an elevated scores of symptom scales including of nausea and vomiting (30.93±25.5 vs 20.8±25.0 in SCRT group, 31.0±28.1 vs 16.5±24.3 in CCRT group), and appetite loss (39.6±30.9 vs 34.8±32.1 in CCRT group) was noted when comparing with that in baseline. The score of item concerning financial difficult declined in CCRT and SCRT group, which was similar as RT group. The scores of GH, functional dimensions and other symptom scales were not different compared with baseline in these two groups. During treatment period, a highest score of global health, functional dimensions including physical, role, cognitive, social functioning, and lowest scores of symptom including fatigue, nausea and vomit, insomnia, appetite loss, constipation and diarrhea was presented in the RT group than the other two groups (GH score 66.5±16.4 in RT group, 60.7±17.9 in CCRT group and 61.9±17.5 in SCRT group, p=0.001). No differences between CCRT and SCRT group regarding GH, functional dimensions and symptom scores. In 12 and 24 months after the completion of treatments, further improved GH, functional dimension scores and declined symptom scores were observed in the whole population, with no significant differences among the 3 treatment groups. <h3>Conclusions:</h3> In CCRT and SCRT group, adding chemotherapy in adjuvant treatment had negative effects on GH, physical, cognitive, social and role function, as well as symptoms related to QoL during the treatment period compared with RT. While the symptoms resolved, functioning and general QoL improved after 12 months of treatment, indicating a transient impact on QoL of patients receiving adjuvant treatment.

Which patients with stage IB endometrioid endometrial cancer are at high risk of distant recurrences?

Objectives: Women with stage IB endometrioid endometrial cancer (EEC) are at risk of developing non-vaginal recurrences. However, it is unclear which patients have high enough risk to justify testing systemic therapies. Our aim is to identify significant risk factors for non-vaginal recurrence. Methods: This is a retrospective multicenter study, including patients who underwent complete surgical staging for EEC at Mayo Clinic, Rochester (MN, USA) between January 1999-December 2017, and at Fondazione Policlinico Gemelli (Rome, Italy) between March 2002-March 2017, with a final FIGO stage IB. Patients without lymph node assessment were excluded. Recurrences were categorized into isolated vaginal and non-vaginal (hematogenous, peritoneal, lymphatic, or multi-site). The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Cox proportional hazards models, stratified by center, were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. Results: Three hundred eighty-six patients were identified. The mean myometrial invasion (MI) of the cohort was 70.4% (SD 13.2). The majority of the patients received either vaginal brachytherapy (VB) or no adjuvant therapy (N=256, 66.3%), 57 patients (14.8%) received EBRT ± chemotherapy ± VB, 38 (9.8%) received chemotherapy ± VB, and 35 (9.1%) unknown. Greater MI was associated with increased histologic grade and lymph vascular space invasion (LVSI). We identified 51 recurrences (14 isolated vaginal, and 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR, 2.3-6.9) years. The 5-year RFS for non-vaginal recurrences was 88.1% (95% CI 84.4-91.9%). There was a strong linear relationship between the percent of MI and the risk of recurrence. Patients with the deepest MI (≥90%) had a rate of recurrence as high as 40%. At univariate analysis, the risk of non-vaginal recurrence increased as the percent of MI increases (vs. MI 50-69.9%), with a hazard ratio (HR) of 3.33 (95% CI, 1.46-7.58) in patients with MI 70 to 89%, and HR of 8.47 (95% CI, 3.26-22.01) with MI≥ 90%. Patients with grade 3 disease had a higher risk of non-vaginal recurrence compared to grade 1-2 (HR 3.58, 95% CI, 1.86-6.88). At multivariate analysis, both histologic grade and depth of MI were independent predictors of recurrence. In particular, the subset of patients with MI≥ 70% and grade 3 tumors have the poorest RFS; however, we noticed also that patients with myometrial invasion ≥ 90% have a very high risk of recurrence independently from histologic grade (Table). Download : Download high-res image (68KB) Download : Download full-size image Conclusions: Considering women with stage IB endometrioid endometrial cancer, the rate of non-vaginal recurrences at 5 years is very high (> 30%): (1) in patients with any grade with MI≥ 90%; and (2) in grade 3 patients with MI≥ 70%. In the future, these pathologic findings could help us identify subgroups of patients in which systemic therapies may be tested.

The role of adjuvant chemotherapy in FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with surgery and postoperative radiotherapy

Objectives: The optimal treatment of FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma remains unknown. It is unclear if adjuvant chemotherapy (CHT) in addition to adjuvant radiotherapy enhances survival in this subgroup of endometrial cancer patients. The goals of the present study were to perform a National Cancer Database (NCDB) analysis in this cohort of patients to 1) compare overall survival following treatment with a hysterectomy and adjuvant radiotherapy with or without CHT, 2) evaluate CHT utilization in the United States, and 3) investigate which factors are associated with survival in stage IB grade 3 endometrioid adenocarcinoma patients. Methods: Patients diagnosed between 2004 and 2015 with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with hysterectomy and postoperative radiotherapy with or without adjuvant systemic CHT were identified in the NCDB. Overall survival (OS) was assessed with Kaplan-Meier curves, and differences between groups were compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders, and logistic regression was used to reveal predictors of CHT use. Results: While the receipt of CHT was associated with a trend toward increased 5-year OS from 68.1% to 74.7% (p=0.059), this association did not reach statistical significance on propensity score weighted (p=0.073) and multivariate analyses (adjusted HR (aHR) 0.86; CI: 0.70-1.06; p=0.15) as shown in the figure. Moreover, there was some evidence of a differential CHT effect in patients who did not undergo a lymphadenectomy (LND; p=0.056); CHT was associated with a trend toward reduced hazard of death in patients with LND (aHR=0.82, CI: 0.66-1.01, p=0.0634) but not in patients who did not undergo LND (aHR=1.70, CI: 0.86-3.35, p=0.1255). Patients who underwent brachytherapy as opposed to external beam radiotherapy, had lymphovascular space invasion (LVSI), were 59 years or younger, were diagnosed in the more recent years of the study and treated in higher facility case volume centers were more likely to: receive adjuvant chemotherapy. No LND (HR 1.51; CI: 1.13-2.03; p=0.0057), positive LVSI (HR 1.71; CI: 1.36-2.16; p 70 (HR 2.61; CI: 2.03-3.36; p Download : Download high-res image (275KB) Download : Download full-size image Conclusions: Adjuvant CHT plus radiotherapy was associated with a non-statistically significant increase in OS in FIGO stage IB grade 3 endometrioid adenocarcinoma patients compared to those treated with adjuvant radiotherapy alone. This potential effect is most apparent in patients who underwent LND.

Machine Learning Models to Predict Survival Outcomes According to the Surgical Approach of Primary Radical Hysterectomy in Patients with Early Cervical Cancer

Simple SummaryAn increased risk of relapse and death from minimally invasive radical hysterectomy has been reported in some patients with early cervical cancer. Thus, the development of an intuitive and precise decision-aid tool, which estimates recurrence and mortality rates by surgical approach, is necessary. To develop models predicting survival outcomes according to the surgical approach, we collected clinicopathologic and survival data of patients with 2009 FIGO stage IB cervical cancer who underwent a radical hysterectomy. Using only variables that could be obtained preoperatively, we developed various models predicting the probability of 5-year progression-free survival and overall survival. Among them, hybrid ensemble models, combined with logistic regression and multiple machine learning models, achieved the best predictive performance. The developed models are expected to help physicians’ and patients’ decision making related to the surgical approach for primary radical hysterectomy.We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients’ clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH.

Radical hysterectomy without adjuvant radiotherapy in patients with cervix carcinoma FIGO 2009 IB1, with or without positive Sedlis criteria

IntroductionLymphovascular space invasion (LVSI), deep (>1/3) stromal invasion (DSI) and large tumor size (>4 cm) have been identified as predictors for intermediate risk for recurrence according to Sedlis (at least two of the prior risk factors) in FIGO stage I cervical cancer. Adjuvant radiotherapy (RT) has been advocated in these patients(1,2), but remains controversial. MethodAll consecutive patients (1997–2017) with cervical cancer FIGO (2009) stage IB1 (≤4 cm) were included. Primary aim was to analyze the recurrence rate. Secondary aim was to identify the risk factors for disease recurrence and survival. ResultsOne-hundred-and-eighty-two patients were included in this retrospective study. Median follow-up was 13 years (range 8–17). Postoperatively, 21 patients received adjuvant therapy due to presence of positive lymph nodes, positive section margins or if a simple hysterectomy was performed (RT: n = 7, concomitant chemo radiotherapy (CCRT): n = 14). None of the patients with a combination of intermediate risk factors according to Sedlis (excluding patients >4 cm) underwent adjuvant RT/CCRT. Disease recurrence was observed in 19 patients (10%). Eleven patients died of disease. LVSI influenced progression-free survival (PFS) (HR 3.950, p = 0.0163) and disease-specific survival (DSS) (HR 4.637, p = 0.0497) significantly. However, the combination of LVSI, tumor size and DSI according to Sedlis did not influence overall survival (OS), DSS or PFS. ConclusionRecurrence rate was low (10%), despite the fact that patients with intermediate risk factors according to Sedlis did not receive postoperative RT/CCRT. LVSI was the sole risk factor influencing PFS and DSS. Combinations of risk factors according to Sedlis did not predict worse outcome.

Adjuvant hysterectomy following primary chemoradiation for stage IB2 and IIA2 cervical cancer: a retrospective comparison of complications for open versus minimally invasive surgery

BackgroundAdjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer has been shown to decrease local relapse rate. The objective of this study is to compare complications and recurrences between minimally invasive and open adjuvant hysterectomy for early stage cervical cancer.MethodsPatients were identified who had undergone adjuvant hysterectomy following chemoradiation for 2009 FIGO stage IB2 and IIA2 cervical cancer from August 2006 to June 2018. Demographic information, treatment course, complications, recurrence data were retrospectively extracted from the medical record. Frequency of complications was compared with Fisher exact test or chi-square test as appropriate and inverse probability of treatment propensity score weighting was used to calculate the disease-free survival.ResultsFifty-four patients met inclusion criteria with a median follow up time of 60.4 months (interquartile range 28.0–98.1 months). There were 24 (44%) open versus 30 (56%) minimally invasive hysterectomies performed. The overall grade 2 or worse complication rate was 43%. There were 8 (27%) patients with complications in the minimally invasive group compared to 4 (17%) in the open group (OR 1.82 (95% CI 0.5–7.0)). There were 9 vaginal cuff defects, dehiscences and/or fistulas in the minimally invasive group compared to 3 in the open group (OR 3.0 (95% CI 0.8–11.2)). There was no statistically significant difference between disease free survival and overall survival among the two groups, however there was a trend towards decreased disease-free survival in the minimally invasive group.ConclusionsAmong women undergoing adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer, there was no difference in complication rates between an open or minimally invasive surgical approach. However, the overall complication rate was high, including a high rate of vaginal cuff defect, dehiscence and/or fistulas. Our findings suggest that an adjuvant hysterectomy should be reserved for patients in which chemoradiation is not anticipated to successfully treat the primary tumor and, if performed, an open approach should be considered.

Laparoscopic Radical Hysterectomy Results in Higher Recurrence Rate Versus Open Abdominal Surgery for Stage IB1 Cervical Cancer Patients With Tumor Size Less Than 2 Centimeter: A Retrospective Propensity Score-Matched Study.

ObjectiveTo compare the oncologic outcomes between laparoscopic and open radical hysterectomy in patients with stage IB1 cervical cancer lesion less than 2 cm.MethodsPatients diagnosed FIGO (2009) stage IB1 (tumor diameter <2 cm) and underwent radical hysterectomy in our hospital between March 2008 and November 2018 were studied. A propensity-matched comparison (1:2) was conducted to minimize selection biases. Demographic and baseline oncologic characteristics were balanced between groups. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan–Meier model, along with univariable and multivariable regression analysis.ResultsA total of 261 patients were enrolled in this study after propensity-matching, with 174 in the open group and 87 in the laparoscopic group. Disease relapsed in seven patients in laparoscopy group, and the recurrence rate was 8.0% (7/87). There were eight patients underwent abdominal radical hysterectomy experienced recurrence, and the recurrence rate was 4.6% (8/174). The multivariate analysis model revealed that laparoscopic operation was associated with higher risk of recurrence than abdominal radical hysterectomy (HR, 3.789; 95% CI, 1.143–12.559; p = 0.029). There were five patients or 2.9% (5/174) died in open surgery group and the corresponding percentage in laparoscopy group was 2.3% (2/87). No difference was found in OS between the two groups (HR, 1.823; 95% CI, 0.2673–12.44; log-rank p = 0.5398). All the recurrence occurred within two years after operation in the laparoscopy group, among which pelvic recurrence (85.7%) was dominant.ConclusionTraditional laparotomy radical hysterectomy has a lower recurrence rate when compared with laparoscopic operation in those cervical cancer patients with a foci diameter less than 2 cm. However, no detrimental effect on survival was found in minimal invasive operation group. Further multi-center prospective trials are needed to confirm our results on a large scale.

Treatment strategy for locally advanced squamous cell cervical cancer with clinically positive pelvic lymph nodes metastasis.

To determine the optimal treatment for locally advanced squamous cell cervical cancer with clinical positive pelvic lymph nodes metastasis (cN1). We enrolled patients with squamous cell cervical cancer with 2008 FIGO stages IB, IIA, or IIB diagnosed with cN1, who were treated at Hyogo Cancer Center between April 2010 and December 2016. Patients with para-aortic lymph nodes metastasis were excluded. Of the 69 eligible patients, 24 underwent concurrent chemoradiotherapy (CCRT), 11 underwent radical hysterectomy with pelvic lymphadenectomy (RH) with or without adjuvant RT, and 34 underwent neoadjuvant chemotherapy (NAC) followed by RH as initial treatment. The regimens of NAC included dose-dense TC (paclitaxel 80 mg/m2 , days 1, 8, 15; and carboplatin at an area under the curve=6 on day 1, every 3 weeks) and dose-dense TP (paclitaxel 80 mg/m2 on days 1, 8, 15; and cisplatin 75 mg/m2 on day 1, every 3 weeks). The median observation period was 57 (12-107) months. The 5-year disease-free survival rates of the CCRT, RH, and NAC groups were 78.7%, 63.6%, and 88.2%, respectively (p=0.14). The 5-year overall survival rates of the CCRT, RH, and NAC groups were 78.6%, 70.1%, and 94.1%, respectively (p=0.11). We recommend avoiding RH as primary treatment for cN1 with locally advanced squamous cell cervical cancer. Although CCRT should be considered for cN1, further studies are required to determine if NAC followed by RH will serve as an effective option.