Stage distribution and prognostic accuracy of the 2023 FIGO (the International Federation of Gynecology & Obstetrics) staging system for endometrial cancer: A retrospective cohort study.

OBJECTIVE: To assess the stage distribution and stage-related disease-specific survival rates for endometrial cancer using the FIGO (the International Federation of Gynecology & Obstetrics) 2009 and 2023 staging systems. Further, we sought to evaluate the prognostic utility of additional covariates beyond the FIGO 2023 stage. METHODS: Endometrial carcinomas were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer and staged according to FIGO 2009 and 2023 criteria. Disease-specific survival was calculated as the time from surgery to death from endometrial cancer. RESULTS: Data from 604 patients were analyzed. Median follow-up time was 81 months. A total of 118 stage shifts (19.5%) occurred between the FIGO 2009 and FIGO 2023 systems, with upshifts accounting for 107 (90.7%) of these changes. Within the FIGO 2023 system, molecular classification resulted in restaging of 69 patients (11.4%). Shifts that could alter adjuvant therapy decisions were identified in 23 patients (3.8%). The FIGO 2023 system effectively categorized endometrial cancers into prognostic subgroups. The FIGO 2023 stage, tumor size, positive peritoneal cytology, and mismatch repair deficiency were associated with disease-specific survival in a multivariable analysis, whereas age and adjuvant therapy were not. CONCLUSION: The FIGO 2023 staging system for endometrial cancer appears highly prognostic. Prognostic assessment of the patients can be further enhanced by readily accessible covariates. A stage shift between the FIGO 2009 and 2023 systems occurs in about one-fifth of patients. The implementation of molecular classification within the FIGO 2023 system bears implications for decisions regarding adjuvant therapy.

Prognostic performance of the 2023 FIGO staging schema for endometrial cancer.

OBJECTIVE: To assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. METHODS: This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. RESULTS: Upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8-96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8-89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). CONCLUSION: The 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication.

Differentiation of survival outcomes by anatomic involvement and histology with the revised 2023 International Federation of Gynecology and Obstetrics staging system for endometrial cancer.

OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer underwent revision in 2023, incorporating histology, lymphovascular space invasion, and molecular classification. Herein, we compare overall survival (OS) outcomes by anatomic and histologic involvement for patients staged by the 2009 system versus 2023 system. METHODS: The National Cancer Database (NCDB) was queried for patients with newly-diagnosed uterine adenocarcinoma from 2004 to 2015, with follow-up data extending through 2020. Stage was determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 134,677 patients were analyzed. Per 2023 classification, patients with stage I disease decreased from 96,161 to 70,101 (-27.1%, p < 0.01), while stage II disease increased from 9295 to 36,294 (+390.5%, p < 0.01). Greatest OS change was observed for 2023 stage IA3 patients (low-risk, synchronous endometrial and ovarian tumors with a clonal relationship), whose 10-year OS was 73.4%, compared to 52.6% for 2009 stage IIIA disease. Ten-year OS for 2023 stage IIIB2 (pelvic peritoneal involvement), previously 2009 stage IVB, was 49.4%, compared to 18.7% for 2009 stage IVB patients. Akaike information criterion, Bayesian information criterion, and Harrel's concordance index were used to evaluate OS prognostication of each staging system across all stages, with likelihood ratio favoring the 2023 system (p = 0.020). CONCLUSIONS: With FIGO's 2023 endometrial cancer anatomic and histologic staging system, stage migration is greatest in early-stage disease. New staging groups may offer more precise prognostication. These changes may affect future management.

Endometrial cancer risk factors, treatment, and survival outcomes as per the European Society for Medical Oncology (ESMO) - European Society of Gynaecological Oncology (ESGO) - European Society for Radiotherapy and Oncology (ESTRO) risk groups and International Federation of Gynecology and Obstetrics (FIGO) staging: An experience from developing world.

Introduction: There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGO-ESTRO and their recommendations for adjuvant treatment have redefined the management protocols. In this retrospective analysis, the outcomes are assessed in the light of the new risk groups and FIGO staging. Material Methods: One hundred and two patients of endometrial cancer reporting to the Department of Radiation Oncology from 2015 to 2019 were analysed retrospectively. Patients were stratified as per the ESMO-ESGO-ESTRO risk groups and FIGO staging. Patients were analysed for demographic profile, histopathology details, FIGO stage, treatment modalities received as per the ESMO-ESGO-ESTRO risk groups and the outcomes in terms of disease free survival and overall survival. Results: A total of 102 patients were analysed. The mean age at presentation was 57.7 years. Seventy four percent (74.41%) were stage I patients, 14.7 % were stage II, 8.8% were stage III and remaining 2% were stage IV. The mean disease free survival for the patients in FIGO stage I, II, III and IV were found to be 63.5 (59.9 - 67) months, 60.5 (54.2 - 66.9) months, 30.9 (21.5 - 40.2) months and 15.4 (7.8 - 23.0) months respectively. The 5-year overall survival of patients in Stage I was 90.3%. The 3-year mortality of Stage III patients was 58.3%. While there was no mortality observed among Stage II patients, none of the Stage IV patient survived beyond 20 months. The 5-year disease-free survival for patients in Low Risk (LR) group, Intermediate Risk (IR) group and High Risk (HR) group was found to be 91.3%, 90% and 87% respectively. None of the patient in High Intermediate Risk (HIR) group experienced progression of disease and 33.3% patients in advanced group were disease free at 2 years follow-up. The multivariate analysis showed that lymph node involvement is significantly associated with disease-free (p=0.03) and overall survival (p=0.04). Conclusion: Even in the developing world, majority of patients present in early stage with survival outcomes comparable to the West. FIGO stage and lymph node involvement continue to be the most important prognostic markers for disease outcomes.

The Significance of International Federation of Gynecology and Obstetrics Grading in Microsatellite Instability-High and POLE-Mutant Endometrioid Endometrial Carcinoma.

With the advancement of diagnostic molecular technology and the molecular classification of endometrial endometrioid carcinoma (EEC), it remains to be seen whether conventional International Federation of Gynecology and Obstetrics (FIGO) grading retains clinical significance in certain molecular subtypes of EECs. In this study, we explored the clinical significance of FIGO grading in microsatellite instability-high (MSI-H) and POLE-mutant EECs. A total of 162 cases of MSI-H EECs and 50 cases of POLE-mutant EECs were included in the analysis. Significant differences in tumor mutation burden (TMB), progression-free survival, and disease-specific survival were seen between the MSI-H and POLE-mutant cohorts. Within the MSI-H cohort, there were statistically significant differences in TMB and stage at presentation across FIGO grades, but not survival. Within the POLE-mutant cohort, there was significantly greater TMB with increasing FIGO grade, but there were no significant differences in stage or survival. In both the MSI-H and POLE-mutant cohorts, log-rank survival analysis showed no statistically significant difference in progression-free and disease-specific survival across FIGO grades. Similar findings were also seen when a binary grading system was utilized. Since FIGO grade was not associated with survival, we conclude that the intrinsic biology of these tumors, characterized by their molecular profile, may override the significance of FIGO grading.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study.

INTRODUCTION: FIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size. MATERIAL AND METHODS: We retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I-IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC-T1, IIIC-T2a, IIIC-T2b, and IIIC-(T3a+T3b). Oncologcial outcomes of all stages were compared. RESULTS: A total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan-Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC-(T1-T2b) was significantly better than of IIIA+IIIB and IIIC-(T3a+T3b); no significant difference was noted between IIB and IIIC-(T1-T2b), or IIIC-(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC-T1, Stages T2a, T2b, IIIA+IIIB and IIIC-(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC-(T1-T2b) and IIB. Also, compared with IIB, IIIC-(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC-(T3a+T3b) and IIIA+IIIB. CONCLUSIONS: In terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC-T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.

National and international guidelines on the management of twin pregnancies: a comparative review.

Twin gestations are associated with increased risk of pregnancy complications. However, high-quality evidence regarding the management of twin pregnancies is limited, often resulting in inconsistencies in the recommendations of various national and international professional societies. In addition, some recommendations related to the management of twin gestations are often missing from the clinical guidelines dedicated to twin pregnancies and are instead included in the practice guidelines on specific pregnancy complications (eg, preterm birth) of the same professional society. This can make it challenging for care providers to easily identify and compare recommendations for the management of twin pregnancies. This study aimed to identify, summarize, and compare the recommendations of selected professional societies from high-income countries on the management of twin pregnancies, highlighting areas of both consensus and controversy. We reviewed clinical practice guidelines of selected major professional societies that were either specific to twin pregnancies or were focused on pregnancy complications or aspects of antenatal care that may be relevant for twin pregnancies. We decided a priori to include clinical guidelines from 7 high-income countries (United States, Canada, United Kingdom, France, Germany, and Australia and New Zealand grouped together) and from 2 international societies (International Society of Ultrasound in Obstetrics and Gynecology and the International Federation of Gynecology and Obstetrics). We identified recommendations regarding the following care areas: first-trimester care, antenatal surveillance, preterm birth and other pregnancy complications (preeclampsia, fetal growth restriction, and gestational diabetes mellitus), and timing and mode of delivery. We identified 28 guidelines published by 11 professional societies from the 7 countries and 2 international societies. Thirteen of these guidelines focus on twin pregnancies, whereas the other 16 focus on specific pregnancy complications predominantly in singletons but also include some recommendations for twin pregnancies. Most of the guidelines are recent, with 15 of the 29 guidelines published over the past 3 years. We identified considerable disagreement among guidelines, primarily in 4 key areas: screening and prevention of preterm birth, using aspirin to prevent preeclampsia, defining fetal growth restriction, and the timing of delivery. In addition, there is limited guidance on several important areas, including the implications of the "vanishing twin" phenomenon, technical aspects and risks of invasive procedures, nutrition and weight gain, physical and sexual activity, the optimal growth chart to be used in twin pregnancies, the diagnosis and management of gestational diabetes mellitus, and intrapartum care.This consolidation of key recommendations across several clinical practice guidelines can assist healthcare providers in accessing and comparing recommendations on the management of twin pregnancies and identifies high-priority areas for future research based on either continued disagreement among societies or limited current evidence to guide care.

Validation of the 2018 FIGO Staging System for Predicting the Prognosis of Patients With Stage IIIC Cervical Cancer.

Background: Risk stratification of patients with cervical cancer accompanied by positive lymph nodes (stage IIIC) (the 2018 International Federation of Gynecology and Obstetrics [FIGO] new staging system) yields a clinically heterogeneous group. In this study, we investigated the prognostic performance of the 2018 FIGO staging system for stage IIIC cervical cancer. Methods: The study included patients with stage III cervical cancer based on the 2018 FIGO staging system, who visited Chongqing University Cancer Hospital between January 2011 and December 2014. Kaplan-Meier curves were generated to evaluate overall survival (OS), which was compared using the log-rank test. The Cox proportional hazard regression model was used for multivariable analysis. Results: A total of 418 patients were eligible for analysis. The 5-year OS was 54.1% for stage IIIC1, 43.3% for stage IIIA, 40.6% for stage IIIB, and 23.1% for stage IIIC2 (P < .001). Multivariable analysis revealed that compared with stages IIIA (hazard ratio [HR] 1.432, 95% confidence interval [CI] 0.867-2.366, P = .161) and IIIB (HR 1.261, 95% CI 0.871-1.827, P = .219), stage IIIC1 cancer was not significantly associated with an increased mortality risk. Stage IIIC2 was independently associated with an increased mortality risk compared with stages IIIA (HR 2.958, 95% CI 1.757-4.983, P < .001) and IIIB (HR 2.606, 95% CI 1.752-3.877, P < .001). We stratified patients with stage IIIC1 based on the T stage. The 5-year OS was significantly longer in patients with stage IIIC1 (T1) than in those with stage IIIA (P = .004) or IIIB (P < .001). Analysis of multiple factors revealed that the mortality risk was 2.75-fold higher in patients with stage IIIC1pN>2 than in patients with stage IIIC1pN1-2 (HR 2.753, 95% CI 1.527-4.965, P = .001). Conclusions: Patients with stage IIIC1 cervical cancer showed heterogeneous clinical characteristics that reflected variable prognoses, depending on the T stage and the extent of pelvic lymph node metastases.

Survival Outcomes of Patients with International Federation of Gynecology and Obstetrics Stage IV Ovarian Cancer: Cytoreduction Still Matters.

PURPOSE: There is still no consensus on the therapeutic strategies for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer (OC). We aim to outline the clinical characteristics and optimal therapeutic strategies of patients with FIGO stage IV OC. METHODS: This single center retrospective study analyzed the clinical features and survival of patients with FIGO stage IV OC that underwent cytoreduction or received at least one course of chemotherapy between January 2014 and December 2020. RESULTS: One hundred and twenty patients were included. Surgery, especially optimal cytoreduction without residual mass improved the overall survival of patients in surgery group (P = .047, HR .432, 95% CI .181-.987). Secondly, the completion of chemotherapy improved median overall survival of patients either with (53.0 months vs 25.0 months, P < .001, HR 7.015, 95% CI 1.372-35.881) or without cytoreduction (43.0 months vs 6.0 months, P = .006, HR 5.969, 95% CI 1.115-31.952). In patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had better survival. CONCLUSIONS: In patients with FIGO stage IV, complete resection of intra-abdominal tumor foci and completion of chemotherapy provided considerable survival benefits to patients with FIGO stage IV OC. Among patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had a better prognosis.

A Rare Case of Small-Cell Neuroendocrine Cancer of the Cervix: An Unexpected Diagnosis.

Cervical cancer is a significant healthcare problem worldwide, especially in developing countries. It is the second most common cause of cancer-related deaths in women. Small-cell neuroendocrine cancer of the cervix (SCNCC) accounts for about 1-3% of all cervical cancers. In this report, we present a case of a patient with SCNCC, whose disease had metastasized to the lungs even without an obvious growth in the cervix. A 54-year-old multiparous woman presented with post-menopausal bleeding for 10 days; she had a history of a similar episode in the past. Examination revealed an erythematous posterior cervix and upper vagina without any obvious growth. Histopathology showed SCNCC on the biopsy specimen. Following further investigations, the stage assigned was IVB, and she was started on chemotherapy. SCNCC is an extremely rare but highly aggressive type of cervical cancer and it requires a multidisciplinary therapeutic approach for an optimal standard of care.

Hazard and cumulative incidence of umbilical cord metabolic acidemia at birth in fetuses experiencing the second stage of labor and pathologic intrapartum fetal heart rate requiring expedited delivery.

PURPOSE: The aim of the study was to determine the cause-specific hazard (CSH) and the cumulative incidence function (CIF) for umbilical cord metabolic acidemia at birth (MA; pH < 7.0 and/or BE [Formula: see text] - 12 mmol/L) at delivery in patients experiencing the 2nd stage of labor (2STG), stratified for both FIGO-2015 pathologic intrapartum cardiotocography requiring expedited delivery (CTG_RED) and duration of 2nd stage of labor. METHODS: 3459 pregnancies experiencing the 2nd stage of labor and delivering at the Division of Obstetrics and Prenatal Medicine, IRCCS Sant'Orsola-Malpighi Hospital, Bologna (Italy), were identified between 2018 and 2019. Survival analysis was used to assess CSH and CIF for MA, stratified for FIGO-2015 pathologic CTG and relevant covariates. RESULTS: FIGO-2015 pathological CTG with expedited operative delivery or urgent cesarean section within 10 or 20 min from diagnosis, respectively occurred in 282/3459 (8.20%). The rate of MA at delivery was 3.32% (115/3459). The spline of CSH for MA showed a direct correlation with the duration of 2STG always presenting higher values and greater slope in the presence of pathologic CTG, with plateau between 60 and 120 min and rapid increase after 120 min. The CIF at 180 min in the 2STG was 2.67% for nonpathological and 10.63% for pathological CTG_RED. Nulliparity, pathological CTG, and meconium-stained amniotic fluid resulted significant predictors of MA in our multivariable model. CONCLUSION: The risk for MA increases moderately across the 2STG with nonpathological CTG and quadruples with pathological CTG_RED. Adjustment for other predictors of MA including meconium-stained amniotic fluid and nulliparity reveals a significant hazard increase for MA associated with pathologic CTG_RED.

Magnetic resonance imaging pitfalls in determining myometrial invasion in stage I endometrial cancer: A case report and literature review.

The degree of myometrial invasion (MI) is crucial in the preoperative diagnosis of endometrial cancer (EC) using MRI in terms of therapeutic and prognostic implications. However, several pitfalls should be kept in mind when using this modality. We report a case of EC on a 64-year-old woman, identified preoperatively without MI based on ultrasonography and MRI, implying a low risk of lymph node metastasis; surprisingly, the uterine incision showed the lesion had invaded <50% of the myometrium. Thus, a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed, and histopathologic analysis confirmed that the EC was on stage IA (cancer is in the endometrium only or less than halfway through the myometrium). In our case, thinning myometrium and uterine atrophy due to aging, multiple leiomyomas, previous curettage, and blood clots were all pitfalls for MRI in detecting MI. By detecting tiny or isointense tumors and depicting distinct vascularity of the malignancy in postmenopausal women, functional MRI techniques such as diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) can help reduce pitfalls when assessing MI. Clinicians can employ DWI preoperatively, which is more reliable and superior to DCE-MRI in determining tumor areas without contrast injection and perform a postoperative histopathological examination to confirm MI in EC.

Discussion on the rationality of FIGO 2018 stage IIIC for cervical cancer with oncological outcomes: a cohort study.

Background: This study explored the rationality of the 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC for cervical cancer to determine outcomes. Methods: We conducted a retrospective study of cervical cancer patients who had received radical surgery or Radiotherapy. Multivariate analysis was used to compare 5-year overall survival (OS) and disease-free survival (DFS) for FIGO 2018 stages IIIA, IIIB, and IIIC cervical cancer patients. Based on tumor-node-metastasis (TNM) staging, IIIC cases were divided into 5 subgroups: T1a, T1b, T2a, T2b, and T3. The 5-year OS and DFS of the different IIIC subgroups were further compared using multivariate analysis. Results: (I) The 5-year OS for FIGO 2018 IIIA (n=251), IIIB (n=1,824), and IIIC (n=3,137) were 73.7%, 69.0%, and 74.3%, respectively (P<0.001), and DFS rates were 64.3%, 60.6%, and 68.0%, respectively (P<0.001). Multivariate analysis indicated that IIIA was associated with 5-year OS [hazard ratio (HR) =0.998, 95% confidence interval (CI): 0.739-1.349, P=0.990], but there was no significant correlation with DFS (HR =1.081, 95% CI: 0.843-1.387, P=0.539). Compared with IIIC, IIIB had a lower 5-year OS (HR =1.291, 95% CI: 1.135-1.468, P<0.001) and DFS (HR =1.354, 95% CI: 1.215-1.508, P<0.001). (II) The 5-year OS of the T1a group (n=4), T1b group (n=861), T2a group (n=587), T2b (n=641) group, and T3 group (n=1,044) were 100.0%, 81.9%, 76.1%, 74.0%, and 65.0%, respectively (P<0.001), and the 5-year DFS were 100.0%, 74.5%, 65.9%, 72.6%, and 61.3%, respectively (P<0.001). Multivariate analysis indicated that compared with the T1b group, T2a (HR =1.405, 95% CI: 1.076-1.834, P=0.012), T2b (HR =1.592, 95% CI: 1.203-2.108, P=0.001), and T3 (HR =2.495, 95% CI: 1.971-3.157, P<0.001) were associated with a lower 5-year OS. T2a (HR =1.372, 95% CI: 1.108-1.699, P=0.004), T2b (HR =1.337, 95% CI: 1.061-1.684, P=0.014), and T3 (HR =2.015, 95% CI: 1.659-2.446, P<0.001) were associated with lower 5-year DFS. Conclusions: The outcome for FIGO 2018 stage IIIC cervical cancer is not worse than that for stage IIIB or IIIA. The outcome for stage IIIC is related to local tumor factors. As the local tumor progresses, the oncological outcome worsens.

Development and validation of a prognostic nomogram for 2018 FIGO stages IB1, IB2, and IIA1 cervical cancer: a large multicenter study.

Background: Nomograms are predictive tools widely used for estimating cancer prognosis. We aimed to develop/validate a nomogram to predict the postsurgical 5-year overall survival (OS) and disease-free survival (DFS) probability for patients with stages IB1, IB2, and IIA1 cervical cancer [2018 International Federation of Gynecology and Obstetrics (FIGO 2018)]. Methods: We retrospectively enrolled cervical cancer patients at 47 hospitals with stages IB1, IB2, and IIA1 disease from the Clinical Diagnosis and Treatment for Cervical Cancer in China database. All patients were assigned to either the development or validation cohort (75% of patients used for model construction and 25% used for validation). OS and DFS were defined as the clinical endpoints. Clinicopathological variables were analyzed based on the Cox proportional hazards regression model. A nomogram was established and validated internally (with bootstrapping) and externally, and its performance was assessed according to the concordance index (C-index), receiver-operating characteristic curve, and calibration plot. Results: In total, 4,065 patients were enrolled and assigned to the development cohort (n=3,074) or validation cohort (n=991). The OS nomogram was constructed based on age, FIGO stage, stromal invasion, and lymphovascular space invasion (LVSI). The DFS nomogram was constructed based on the FIGO stage, histological type, stromal invasion, and LVSI. Both nomograms showed greater discrimination than the FIGO 2018 staging system in the development cohort [OS nomogram vs. FIGO 2018: C-index =0.69 vs. 0.61, area under the curve (AUC): 69.8 vs. 60.3; DFS nomogram vs. FIGO 2018: C-index =0.64 vs. 0.57, AUC: 62.6 vs. 56.9], and the same results were observed the definition in the validation cohort. Calibration plots demonstrated good agreement between the predicted and actual probabilities of 5-year OS/DFS in the development and validation cohorts. We stratified the patients into 3 subgroups with differences in OS/DFS. Each risk subgroup presented a distinct prognosis. Conclusions: We successfully developed a robust and powerful model for predicting 5-year OS/DFS in stages IB1, IB2, and IIA1 cervical cancer (FIGO 2018) for the first time. Internal and external validation showed that the model had great prediction performance and was superior to the currently utilized FIGO staging system.

High-dose-rate brachytherapy boost for locally advanced cervical cancer: Oncological outcome and toxicity analysis of 4 fractionation schemes.

PURPOSE: Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT. PATIENTS AND METHODS: This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported. RESULTS: From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45-132] and median EQD210D90CTVHR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81-90], 83% [79-86], 70% [67-73], 61% [57-64] and 75% [69-78] respectively, with no significant difference between the groups. EQD210D90CTVHR < 85 Gy was a prognostic factor for local recurrence in univariate analysis (p = 0.045). The rates of acute/late grade ≥ 2 urinary, digestive and gynecological toxicities were 9%/15%, 3%/15% and 9%/25% respectively. CONCLUSION: Bi-fractionated HDR-BT boost seems feasible with good oncological outcome and slightly more toxicity after dose escalation.

Clinical Staging of Ovarian Cancer.

Ovarian cancer may arise from any of the histologic portions of the ovary including the epithelium, stroma, or germ cells. Of these, high-grade serous carcinoma arising from the epithelium of the ovary is the most common type. The clinical management and prognosis of ovarian cancer depend upon the stage of the cancer. Cancer stage is the extent to which the cancer has spread from its site of origin. For ovarian cancer, staging guidelines are determined by FIGO, the Fédération Internationale de Gynécologie et d'Obstétrique. The stage of ovarian cancer is determined by performing surgery to remove the ovaries and other gynecologic organs as well as lymph nodes and other tissues where the cancer may have spread. The histologic specimens from this surgery provide information from which the stage can be determined. In more advanced cases, this surgery may also include procedures to remove other areas of cancer. The stage of ovarian cancer guides treatment and is also the most important factor in ovarian cancer prognosis. Most epithelial ovarian cancers are diagnosed in advanced stages and are treated with surgery and chemotherapy. Despite aggressive treatment, the survival of patients with advanced stage epithelial ovarian cancer remains low, and more effective diagnostic and therapeutic approaches are needed.

Preoperative LMR and Serum CA125 Level as Risk Factors for Advanced Stage of Ovarian Cancer.

Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.

Comparison of Postoperative Adjuvant Chemotherapy and Concurrent Chemoradiotherapy for FIGO2018 Stage IIIC1 Cervical Cancer: A Retrospective Study.

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.

The 5-year overall survival of cervical cancer in stage IIIC-r was little different to stage I and II: a retrospective analysis from a single center.

BACKGROUND: The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging guideline for cervical cancer includes stage IIIC recognized by preoperative radiology (IIIC-r) to state there are lymph nodes metastases (LNM) identified by imaging tools. We aim to explore the reasonability and limitations of stage IIIC-r and try to explore the potential reasons. METHODS: Electronic medical records were used to identify patients with cervical cancer. According to the new staging guidelines, patients were reclassified and assigned into five cohorts: stage I, stage II, stage IIIC-r, LNM confirmed by pathology (IIIC-p) and LNM detected by radiology and confirmed by pathology (IIIC r + p). Five-year overall survivals were estimated for each cohort. The diagnosis accuracy of computed tomography (CT), magnetic resonance imaging (MRI) and diameter of detected lymph nodes were also evaluated. RESULTS: A total of 619 patients were identified. The mean follow-up months were 65 months (95% CI 64.43-65.77) for all patients. By comparison, the 5-year overall survival rates were not statistically different (p = 0.21) among stage IIIC-r, stage I and stage II. While, the rates were both statistical different (p<0.001) among stage IIIC-p, IIIC r + p and stage I and stage II. The sensitivities of CT and MRI in detecting LNM preoperatively were 51.2 and 48.8%. The mean maximum diameter of pelvic lymph nodes detected by CT cohort was 1.2 cm in IIIC-r cohort, and was 1.3 cm in IIIC r + p cohort. While, the mean maximum diameter of pelvic lymph nodes detected by MRI was 1.2 cm in IIIC-r cohort, and was 1.48 cm in IIIC r + p cohort. When the diagnosis efficacy of the diameter of pelvic lymph nodes in detecting LNM were evaluated, the area under the receiver operating characteristic curve (ROC curve) was 0.58 (p = 0.05). CONCLUSIONS: It seems that the FIGO 2018 staging guideline for cervical cancer is likely to has certain limitations for the classification of those with LNM. CT or MRI, however, has limitations on detecting LNM. It would be better to use more accurate imaging tools to identify LNM in the clinical practices.

Quantification of Posterior Risk Related to Intrapartum FIGO 2015 Criteria for Cardiotocography in the Second Stage of Labor.

INTRODUCTION: Intrapartum cardiotocography (CTG) was used for several decades to detect a stressed fetus so that delivery can be expedited to prevent birth asphyxia. The main aim of the study was to calculate the risk of neonatal acidemia (pH ≤ 7.10) according to duration of the 2nd stage of labor and occurrence of the International Federation of Gynecology and Obstetrics (FIGO) 2015 CTG classification parameters. MATERIALS AND METHODS: This was a retrospective case-control study on 552 pregnancies receiving continuous CTG monitoring in labor and immediate hemogasanalysis at birth. Cases with umbilical artery (UA) pH ≤ 7.10 and controls with UA pH ≥ 7.10 were matched for parity and gestational age at delivery, with ratio 1:5. Logistic regression analysis, adjusted for the expected risk in the general population, was used to calculate the baseline risk of UA pH ≤ 7.10 in the absence of any CTG pathological feature and those associated with pathological CTG patterns occurring in the 2nd stage according to FIGO 2015. RESULTS: Seventy-three cases and 387 controls reached 2nd stage and were included in the analysis. For those reaching 2nd stage, the mean adjusted risk of acidemia associated with nonpathological CTG was 1.6%. Stratification of risk according to duration of the 2nd stage yielded risks of neonatal acidemia of 1.23, 2.08, 5.81, and 15.22% at 30, 60, 120, and 180 min, respectively. Bradycardia >10 min was associated with risk of neonatal acidemia of 9.9 and 15.8% for 2nd-stage durations of 30 and 60 min, respectively. Risks associated with 1 prolonged deceleration >5 min were 6.80, 11.08, 27.0, and 51.0% at 30, 60, 120, and 180 min, respectively. Repetitive late or prolonged decelerations >30 min were associated with risk of neonatal acidemia of 2.43, 4.14, 11.17, and 26.45% at 30, 60, 120, and 180 min, respectively. CONCLUSION: The risk of neonatal acidemia is directly proportional to duration of the 2nd stage, irrespective of the presence of CTG abnormalities, increasing 12-fold (1.2-15.3%) from 30 to 180 min. Occurrence of FIGO 2015 pathological CTG patterns showed a decreasing impact from bradycardia >10 min to decelerations >5 min, recurrent later or prolonged decelerations >30 min, and nonpathological CTG.