Prognostic Factors for Recurrence in Patients With FIGO Stage I and II Intermediate or High Risk Endometrial Cancer

e17115 Background: It remains unclear which is the best chemotherapy (CT) regimen and what is the role of adding radiotherapy (RT) to adjuvant CT in high-risk endometrial cancer. Methods: We performed a retrospective analysis of the patients (pts) with high-risk endometrial cancer (endometrioid histology stages III-IVA or carcinossarcoma/ clear cells/ serous histology stages I-IVA) treated with adjuvant carboplatin (AUC 5) and paclitaxel (175 mg/m2), every 3 weeks, for 6 cycles, followed by RT (conformal external beam radiotherapy to pelvic or pelvic and paraortic fields with 45Gy-54Gy plus weekly vaginal brachytherapy with 20Gy in 4 fractions). Pts were treated from 2010 to 2016 at a Brazilian public cancer center. Medical records were reviewed for demographic, clinicopathologic and outcome information. Data was analyzed for overall survival (OS), disease-free survival (DFS), prognostic factors and toxicity. The Kaplan-Meier method was used for survival analysis and Cox proportional hazard model for prognostic factors. Results: 146 consecutive pts were evaluated. Median age was 62 years (range 35-81). Most patients had ECOG 0-1 (98%), endometrioid (53%) or serous histology (26%), grade 3 tumor (57%) and FIGO stage III (77%). Median follow-up was 26.5 months. The OS rates were 85% (95% CI 75 – 91%) in 3 years and 73% (95% CI 58 – 84%) in 5 years. Factors that significantly affected OS in a multivariate analysis were FIGO stage (p = .009), pelvic lymphadenectomy (yes vs no, p = .023) and positive peritoneal cytology (yes vs no, p = .002). 3-year and 5-year DFS rates were 79% (95% CI 70 – 86%) and 68% (95% CI 52 – 80%), respectively. The initial site of recurrence was limited to the pelvis in 3% of the pts, within the abdomen in 1% and extra-abdominal in 11%. Grade 3/4 AEs occurred in 47% of the pts and were mainly hematologic toxicity (43%). There were only 3 cases of febrile neutropenia and 4 cases of hospitalization due to toxicity. Conclusions: Our data suggests that adjuvant carboplatin and paclitaxel, followed by RT, in high-risk endometrial cancer is safe and effective. Low rates of pelvic recurrence were observed, which might be explained by the addition of RT to adjuvant CT.

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Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-002217 ◽

2021 ◽

pp. ijgc-2020-002217

Author(s):

Elizabeth B Jeans ◽

William G Breen ◽

Trey C Mullikin ◽

Brittany A Looker ◽

Andrea Mariani ◽

...

Keyword(s):

Endometrial Cancer ◽

Clear Cell ◽

Early Stage ◽

Figo Stage ◽

Stage I ◽

High Dose ◽

Vaginal Cuff ◽

Locoregional Failure ◽

Platinum Based Chemotherapy ◽

Increased Risk

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

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Salvage Radiation for Pelvic Relapse after Surgically Treated Endometrial Cancer

Cancers ◽

10.3390/cancers13061367 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1367

Author(s):

Kristina Lindemann ◽

Elisabeth Smogeli ◽

Milada Cvancarova Småstuen ◽

Kjersti Bruheim ◽

Jone Trovik ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Risk Group ◽

Cox Model ◽

Figo Stage ◽

Target Volume ◽

Lymph Node Involvement ◽

High Risk Group ◽

Curative Intent ◽

Pelvic Relapse

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome.

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ENGOT-en11/GOG-3053/KEYNOTE-B21: Phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with newly diagnosed high-risk endometrial cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps5608 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS5608-TPS5608

Author(s):

Toon Van Gorp ◽

Mansoor Raza Mirza ◽

Alain Lortholary ◽

David Cibula ◽

Axel Walther ◽

...

Keyword(s):

Quality Of Life ◽

Endometrial Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Combination Therapy ◽

Stage I ◽

Newly Diagnosed ◽

Phase 3 ◽

Eortc Qlq

TPS5608 Background: Pembrolizumab, a selective humanized anti–PD-1 monoclonal antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% ORR as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer (EC). ENGOT-en11/GOG-3053/KEYNOTE-B21 is a phase 3, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC. Methods: Eligible patients are ≥18 years old with newly diagnosed, histologically confirmed high-risk (stage I/II non-endometrioid, stage III/IVa, p53 abnormality) EC (carcinoma or carcinosarcoma) following surgery with curative intent with no evidence of disease post-operatively or on imaging, and without prior systemic therapy/radiotherapy. In total, ̃990 patients are randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles + chemotherapy (carboplatin area under the curve [AUC] 5 or 6 + paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2 or 2.7 + paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2 per their treatment assignment. At the investigator’s discretion, radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and International Federation of Gynecology and Obstetrics (FIGO) surgical stage (I/II vs III/IVA). Dual primary endpoints are disease-free survival (DFS; per investigator assessment) and overall survival (OS), both estimated by the Kaplan-Meier method, with a stratified log-rank test to assess treatment differences and a Cox proportional hazard model with Efron’s method of tie handling to assess the magnitude of treatment differences. Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and Endometrial Cancer Module [EORTC QLQ-EN24]). The study began enrollment in December 2020. Clinical trial information: NCT04634877.

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An Integrated Autophagy-Related Long Noncoding RNA Signature as a Prognostic Biomarker for Human Endometrial Cancer: A Bioinformatics-Based Approach

BioMed Research International ◽

10.1155/2020/5717498 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Ziwei Wang ◽

Jun Zhang ◽

Yan Liu ◽

Rong Zhao ◽

Xing Zhou ◽

...

Keyword(s):

Endometrial Cancer ◽

Survival Rate ◽

High Risk ◽

Noncoding Rna ◽

Risk Group ◽

Figo Stage ◽

High Risk Group ◽

Low Risk ◽

Pathological Grade ◽

Risk Status

Endometrial cancer is one of the most common malignant tumors, lowering the quality of life among women worldwide. Autophagy plays dual roles in these malignancies. To search for prognostic markers for endometrial cancer, we mined The Cancer Genome Atlas and the Human Autophagy Database for information on endometrial cancer and autophagy-related genes and identified five autophagy-related long noncoding RNAs (lncRNAs) (LINC01871, SCARNA9, SOS1-IT1, AL161618.1, and FIRRE). Based on these autophagy-related lncRNAs, samples were divided into high-risk and low-risk groups. Survival analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Univariate and multivariate independent prognostic analyses showed that patients’ age, pathological grade, and FIGO stage were all risk factors for poor prognosis. A clinical correlation analysis of the relationship between the five autophagy-related lncRNAs and patients’ age, pathological grade, and FIGO stage was also per https://orcid.org/0000-0001-7090-1750 formed. Histopathological assessment of the tumor microenvironment showed that the ESTIMATE, immune, and stromal scores in the high-risk group were lower than those in the low-risk group. Principal component analysis and functional annotation were performed to confirm the correlations. To further evaluate the effect of the model constructed on prognosis, samples were divided into training (60%) and validation (40%) groups, regarding the risk status as an independent prognostic risk factor. A prognostic nomogram was constructed using patients’ age, pathological grade, FIGO stage, and risk status to estimate the patients’ survival rate. C-index and multi-index ROC curves were generated to verify the stability and accuracy of the nomogram. From this analysis, we concluded that the five lncRNAs identified in this study could affect the incidence and development of endometrial cancer by regulating the autophagy process. Therefore, these molecules may have the potential to serve as novel therapeutic targets and biomarkers.

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Prognostic Factors in Early-Stage Leiomyosarcoma of the Uterus

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181a1bfbc ◽

2009 ◽

Vol 19 (3) ◽

pp. 385-390 ◽

Cited By ~ 40

Author(s):

Manuela Pelmus ◽

Frédérique Penault-Llorca ◽

Louis Guillou ◽

Françoise Collin ◽

Gérard Bertrand ◽

...

Keyword(s):

Prognostic Factors ◽

Prognostic Factor ◽

Vascular Invasion ◽

Early Stage ◽

Prognostic Significance ◽

Figo Stage ◽

Stage I ◽

Free Interval ◽

Important Prognostic Factor ◽

Pathologic Features

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 × 10−15). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.

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Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6)

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002703 ◽

2021 ◽

Vol 31 (7) ◽

pp. 1075-1079

Author(s):

Günter Emons ◽

Jae-Weon Kim ◽

Karin Weide ◽

Nikolaus de Gregorio ◽

Pauline Wimberger ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Controlled Trial ◽

Left Renal Vein ◽

Stage I ◽

Open Label ◽

Risk Of Recurrence ◽

Gynecology And Obstetrics ◽

The Impact

BackgroundThe impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident.Primary ObjectiveEvaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence.Study HypothesisComprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65.Trial DesignOpen label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended.Major Inclusion CriteriaPatients with histologically confirmed endometrial cancer stages pT1b–pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible.Exclusion CriteriaPatients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease.Primary EndpointOverall survival calculated from the date of randomization until death.Sample Size640 patients will be enrolled in the study.Estimated Dates for Completing Accrual and Presenting ResultsAt present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031.Trial RegistrationNCT03438474.

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