Fertility-sparing treatment in women with endometrial cancer

Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500–600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.

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Fertility-sparing treatment by high dose oral medroxyprogesterone acetate for endometrial cancer and atypical hyperplasia in young women: A multicentric phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.5022 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 5022-5022 ◽

Cited By ~ 2

Author(s):

K. Ushijima ◽

H. Yoshikawa ◽

T. Hirakawa ◽

T. Yasugi ◽

T. Saito ◽

...

Keyword(s):

Endometrial Cancer ◽

Phase Ii ◽

Young Women ◽

Medroxyprogesterone Acetate ◽

Phase Ii Study ◽

Atypical Hyperplasia ◽

High Dose ◽

Fertility Sparing ◽

Dose Oral

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Fertility-Sparing Treatment in Young Women with Atypical Endometrial Hyperplasia and Low-Grade Endometrial Cancer: A Tertiary Center Experience

JBRA Assisted Reproduction ◽

10.5935/1518-0557.20200037 ◽

2020 ◽

Author(s):

Sumaya Shikeli ◽

Vaidyanathan Gowri ◽

Thuria Al Rawahi

Keyword(s):

Endometrial Cancer ◽

Young Women ◽

Endometrial Hyperplasia ◽

Low Grade ◽

Atypical Endometrial Hyperplasia ◽

Fertility Sparing ◽

Tertiary Center

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Fertility-Preserving Treatment in Young Women With Endometrial Adenocarcinoma: A Long-Term Cohort Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000098 ◽

2014 ◽

Vol 24 (4) ◽

pp. 718-728 ◽

Cited By ~ 19

Author(s):

Chin-Jung Wang ◽

Angel Chao ◽

Lan-Yan Yang ◽

Swei Hsueh ◽

Yu-Ting Huang ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Young Women ◽

Endometrial Adenocarcinoma ◽

Myometrial Invasion ◽

Megestrol Acetate ◽

Published Data ◽

High Dose ◽

Low Grade

ObjectiveGrowing evidence suggests that fertility-preserving treatment is feasible for young women with early-stage, low-grade endometrial carcinoma. However, published data on their long-term outcomes and prognostic factors remain scanty. We aimed to investigate the outcomes of young women receiving fertility-preserving treatment.MethodsBetween 1991 and 2010, the outcomes of young women with grade 1 endometrioid endometrial carcinoma at presumed stage IA (without myometrial invasion) who underwent fertility-preserving treatment of megestrol acetate 160 mg/d with or without other hormonal agents were retrospectively analyzed.ResultsWe identified 37 eligible patients (median age, 32 years; range, 18–40 years). The median follow-up time was 78.6 months (range, 19.1–252.8 months). Complete response (CR) lasting more than 6 months was achieved in 30 (81.1%) women. Responders were significantly younger than nonresponders (P= 0.032). Of the 30 women who had a CR, 15 (50.0%) had disease recurrence. The 5-, 10-, and 15-year cumulative recurrence-free survival rates were 51.0%, 51.0%, and 34.0%, respectively. Notably, those recurred were significantly older (P= 0.003), and the time to CR was significantly longer (P= 0.043) than those without recurrence. One patient developed late recurrences at 156 months, and 2 patients developed ovarian metastasis (6 and 137 months from diagnosis). All the patients are currently alive.ConclusionsThis study demonstrates the feasibility of high-dose megestrol acetate–based therapy for fertility preservation. The substantial risk of late recurrences highlights the need for long-term follow-up studies of large sample sizes with in-depth tumor and host molecular signatures.

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Ovarian conservation for young women with early-stage low-grade endometrial cancer: A proposal for a two-step approach

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2020.12.1213 ◽

2021 ◽

Author(s):

Koji Matsuo ◽

Rachel S. Mandelbaum ◽

Shinya Matsuzaki ◽

Maximilian Klar ◽

Lynda D. Roman ◽

...

Keyword(s):

Endometrial Cancer ◽

Young Women ◽

Early Stage ◽

Low Grade ◽

Ovarian Conservation

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Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182a5055e ◽

2013 ◽

Vol 23 (9) ◽

pp. 1620-1628 ◽

Cited By ~ 14

Author(s):

Joyce N. Barlin ◽

Robert A. Soslow ◽

Megan Lutz ◽

Qin C. Zhou ◽

Caryn M. St. Clair ◽

...

Keyword(s):

Endometrial Cancer ◽

Myometrial Invasion ◽

Staging System ◽

Stage I ◽

Low Grade ◽

List Type ◽

High Grade ◽

High Grade Carcinoma ◽

Concordance Probability ◽

Grade 3

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

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Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000692 ◽

2016 ◽

Vol 26 (5) ◽

pp. 918-923 ◽

Cited By ~ 7

Author(s):

Xiaoyuan Wang ◽

Li Li ◽

Janiel M. Cragun ◽

Setsuko K. Chambers ◽

Kenneth D. Hatch ◽

...

Keyword(s):

Risk Factors ◽

Endometrial Cancer ◽

Tumor Size ◽

Frozen Section ◽

Medical Center ◽

Myometrial Invasion ◽

Surgical Staging ◽

Endometrioid Adenocarcinoma ◽

Intraoperative Frozen Section

ObjectiveThe aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC).MethodsMedical records were collected retrospectively on 112 patients with endometrioid EC, who underwent total hysterectomy and bilateral salpingo-oophorectomy at the University of Arizona Medical Center from January 1, 2010, to December 31, 2014. Only patients with endometrioid adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise, surgical staging was performed with lymph node dissection. The FS results were compared with the permanent paraffin sections (PSs) to assess the diagnostic accuracy.ResultsThe concordance rate of different variables between FS and PS in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112), respectively, with respecting to histological subtype, grade, myometrial invasion, and tumor size. Diagnostic accurate rate of combined risk factors deciding surgical staging at the time of FS was 95.5% (107/112), and the discordance rate of all risk factors considered between FS and PS was 4.5%, resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated.ConclusionsDespite nonideal FS evaluation, intraoperative FS diagnosis for EC is highly reliable by providing guidance for the intraoperative decisions of surgical staging at our institution, and such guidelines may be referenced by the institutions with sufficient gynecologic pathology expertise.

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High dose rate post-operative vaginal cuff irradiation alone for stage i endometrial cancer with myometrial invasion

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/s0360-3016(98)80488-4 ◽

1998 ◽

Vol 42 (1) ◽

pp. 318

Author(s):

John M. Anderson ◽

Tam Nguyen ◽

Joel Childers ◽

Alton V. Hallum ◽

Earl Surwitt ◽

...

Keyword(s):

Endometrial Cancer ◽

Dose Rate ◽

Myometrial Invasion ◽

High Dose Rate ◽

Stage I ◽

High Dose ◽

Vaginal Cuff

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Can the apparent diffusion coefficient differentiate the grade of endometrioid adenocarcinoma and the histological subtype of endometrial cancer?

Acta Radiologica ◽

10.1177/0284185117716198 ◽

2017 ◽

Vol 59 (3) ◽

pp. 363-370 ◽

Cited By ~ 10

Author(s):

Bin Yan ◽

Tingting Zhao ◽

Xiufen Liang ◽

Chen Niu ◽

Caixia Ding

Keyword(s):

Diffusion Coefficient ◽

Endometrial Cancer ◽

Apparent Diffusion Coefficient ◽

Low Grade ◽

Endometrioid Adenocarcinoma ◽

High Grade ◽

Squamous Differentiation ◽

Apparent Diffusion ◽

Adc Values ◽

Endometrial Cancers

Background Diffusion-weighted imaging (DWI) provides useful information for the identification of benign and malignant uterine lesions. However, the use of the apparent diffusion coefficient (ADC) for histopathological grading of endometrial cancer is controversial. Purpose To explore the use of ADC values in differentiating the preoperative tumor grading of endometrioid adenocarcinomas and investigate the relationship between the ADC values of endometrial cancer and the histological tumor subtype. Material and Methods We retrospectively evaluated 98 patients with endometrial cancers, including both endometrioid adenocarcinomas (n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent DWI procedures and ADC values were calculated. The Kruskal–Wallis test and the independent samples Mann–Whitney U test were used to compare differences in the ADC values between different tumor grades and different histological subtypes. Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas were significantly lower than the values for low-grade tumors (0.800 versus 0.962 × 10–3 mm2/s) ( P = 0.002). However, no significant differences in ADCmean and minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of endometrial cancer. Compared with endometrioid adenocarcinomas, the adenocarcinoma with squamous differentiation showed lower ADC values (mean/minimum = 0.863/0.636 versus 0.962/0.689 × 10–3 mm2/s), but the differences were not significant ( Pmean = 0.074, Pmin = 0.441). Moreover, ADCmean for carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma endometrial cancers (1.047 versus 0.823 × 10–3 mm2/s) ( P = 0.001). Conclusion The ADCmean was useful for identifying high-grade and low-grade endometrioid adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and ADCmin of endometrioid adenocarcinoma, and carcinosarcomas showed relatively high ADCmean.

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