Low-dose adjuvant vaginal cylinder brachytherapy for early-stage non-endometrioid endometrial cancer: recurrence risk and survival outcomes

ObjectiveThe aim of this study was to evaluate recurrence patterns and survival outcomes for patients with early-stage non-endometrioid endometrial adenocarcinoma treated with adjuvant high-dose rate vaginal brachytherapy with a low-dose scheme.MethodsA retrospective review was performed of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–II non-endometrioid endometrial cancer who received adjuvant vaginal brachytherapy with a low-dose regimen of 24 Gy in six fractions from November 2005 to May 2017. All patients had >6 months of follow-up. Rates of recurrence-free survival, overall survival, vaginal, pelvic, and distant recurrence were calculated by the Kaplan–Meier method. Prognostic factors for recurrence and survival were evaluated by Cox proportional hazards modeling.ResultsA total of 106 patients were analyzed. Median follow-up was 49 months (range 9–119). Histologic subtypes were serous (47%, n=50), clear cell (10%, n=11), mixed (27%, n=29), and carcinosarcoma (15%, n=16). Most patients (79%) had stage IA disease, 94% had surgical nodal assessment, and 13% had lymphovascular invasion. Adjuvant chemotherapy was delivered to 75%. The 5-year recurrence-free and overall survival rates were 74% and 83%, respectively. By histology, 5-year recurrence-free/overall survival rates were: serous 73%/78%, clear cell 68%/88%, mixed 88%/100%, and carcinosarcoma 56%/60% (p=0.046 and p<0.01). On multivariate analysis, lymphovascular invasion was significantly associated with recurrence (HR 3.3, p<0.01). The 5-year vaginal, pelvic, and distant recurrence rates were 7%, 8%, and 21%, respectively. Vaginal and pelvic recurrence rates were highest for patients with carcinosarcoma, lymphovascular invasion and/or FIGO stage IB/II disease. At 5 years, vaginal and pelvic recurrence rates for patients with lymphovascular invasion were 33% and 40%, respectively. Patients with stage IA disease or no lymphovascular invasion had 5-year vaginal recurrence rates of 4% and pelvic recurrence rates of 6% and 3%, respectively.ConclusionsAdjuvant high-dose rate brachytherapy with a low-dose scheme is effective for most patients with early-stage non-endometrioid endometrial cancer, particularly stage IA disease and no lymphovascular invasion. Pelvic radiation therapy should be considered for those with carcinosarcoma, lymphovascular invasion and/or stage IB/II disease.

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Lymphovascular Space Invasion and the Treatment of Stage I Endometrioid Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000306 ◽

2015 ◽

Vol 25 (1) ◽

pp. 75-80 ◽

Cited By ~ 10

Author(s):

Louis J.M. van der Putten ◽

Yvette P. Geels ◽

Nicole P.M. Ezendam ◽

Hans W.H.M. van der Putten ◽

Marc P.M.L. Snijders ◽

...

Keyword(s):

Risk Factors ◽

Endometrial Cancer ◽

Adjuvant Radiotherapy ◽

Early Stage ◽

Myometrial Invasion ◽

Distant Recurrence ◽

Stage I ◽

Recurrence Rates ◽

Endometrioid Endometrial Cancer ◽

Lymphovascular Space Invasion

ObjectivesTreatment of clinical early-stage endometrioid endometrial cancer (EEC) in The Netherlands consists of primary hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy is given when 2 or more the following risk factors are present: 60 years or older, grade 3 histology, and 50% or more myometrial invasion. Lymphovascular space invasion (LVSI) is a predictor of poor prognosis and early distant spread. It is unclear whether adjuvant radiotherapy is sufficient in patients with LVSI-positive EEC.Methods/MaterialsEighty-one patients treated from 1999 until 2011 for stage I LVSI-positive EEC in 11 Dutch hospitals were included. The outcomes of patients with 0 to 1 risk factors were compared with those with 2 to 3 risk factors, and both were compared with the known literature.ResultsEighteen patients presented with recurrent disease, and 12 of those recurrences had a distant component. Overall and distant recurrence rates were 19.2% and 11.5% in patients with 0 to 1 risk factors followed by observation and 25.5% and 17% in patients with 2 to 3 risk factors who received adjuvant radiotherapy. Only 1 patient with grade 1 disease had a recurrence.ConclusionsIn stage I LVSI-positive EEC with 0 to 1 risk factors, observation might not be adequate. Moreover, despite adjuvant radiotherapy, a high overall and distant recurrence rate was observed in patients with 2 to 3 risk factors. The use of systemic treatment in these patients, with the exception of patients with grade 1 disease, should be investigated.

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A novel low dose fractionation regimen for adjuvant vaginal brachytherapy in early stage endometrioid endometrial cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2012.07.111 ◽

2012 ◽

Vol 127 (2) ◽

pp. 351-355 ◽

Cited By ~ 29

Author(s):

Kanokpis Townamchai ◽

Larissa Lee ◽

Akila N. Viswanathan

Keyword(s):

Endometrial Cancer ◽

Low Dose ◽

Early Stage ◽

Dose Fractionation ◽

Endometrioid Endometrial Cancer ◽

Fractionation Regimen

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Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000036 ◽

2019 ◽

Vol 29 (1) ◽

pp. 77-85 ◽

Cited By ~ 9

Author(s):

Su Hyun Chae ◽

Seung-Hyuk Shim ◽

Sun Joo Lee ◽

Ji Young Lee ◽

Soo-Nyung Kim ◽

...

Keyword(s):

Endometrial Cancer ◽

Early Stage ◽

Disease Free Survival ◽

Oncologic Outcomes ◽

Survival Duration ◽

Rank Test ◽

Lower Grade ◽

Fertility Sparing ◽

Stage Ia ◽

Endometrioid Endometrial Cancer

ObjectiveHormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer.MethodsWe retrospectively analyzed patients presumed to have stage IA, grade 1–2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups.ResultsSeventy-one patients presumed to have stage IA, grade 1–2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4–49) and 12.0 months (range 3–35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was statistically significant. The median disease-free survival duration was 26 months (range 20–38) and 12 months (range 4–48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test).ConclusionsA lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence.

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Microsatellite Instability as a Maker of Prognosis: a Systematic Review and Meta-analysis of Endometrioid Endometrial Cancer Survival Data

10.21203/rs.3.rs-834538/v1 ◽

2022 ◽

Author(s):

Jing-ping Xiao ◽

Ji-sheng Wang ◽

Yuan-yu Zhao ◽

Jiang Du ◽

Yunzi Wang

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Microsatellite Instability ◽

Early Stage ◽

Meta Analysis ◽

Disease Free Survival ◽

Progression Free Survival ◽

Free Survival ◽

Endometrioid Endometrial Cancer ◽

Disease Free

Abstract Introduction To investigate whether microsatellite instability (MSI) is an important prognostic biomarker for endometrioid endometrial cancer (EEC).Methods The PubMed, EMBASE and the Cochrane Cooperative Library databases were searched from inception to July 2021. Overall survival, disease-free survival, progression-free survival, EEC-specific survival, recurrence-free survival and the recurrence rate were pooled to analyze the correlation between MSI and EEC. In addition, Egger’s regression analysis and Begg’s test were used to detect publication bias.Results 17 studies met the inclusion criteria and were included in our meta-analysis with a sample size of 4723, and the included patients with endometrioid cancer (EC) all were EEC. The pooled hazard ratios (HR) in patients with EEC shown that MSI was significantly associated with shorter overall survival [HR=1.37, 95% confidence interval (CI) (1.00-1.86), p=0.048, I2=60.6%], shorter disease-free survival [HR=1.99, 95% CI (1.31-3.01), p=0.000, I2=67.2%], shorter EEC-specific survival [HR=2.07, 95% CI (1.35-3.18), p=0.001, I2=31.6%] and a higher recurrence rate [Odds ratios (OR)=2.72, 95% CI (1.56-4.76), p=0.000, I2=0.0%]. In the early-stage EEC subgroup, MSI was significantly associated with shorter overall survival [HR=1.47, 95% CI (1.11-1.95), p=0.07], shorter disease-free survival [HR=4.17, 95% CI (2.37-7.41), p=0.000], and shorter progression-free survival [HR=2.41, 95% CI (1.05-5.54), p=0.039]. No significant heterogeneity was observed in overall survival (I2=20.9%), disease-free survival (I2=0.0%), or progression-free survival (I2=0.0%) in patients with early-stage EEC. Meanwhile, publication bias was not observed, and the p-value for Egger’s test of overall survival, disease-free survival, and EEC-specific survival were p=0.131, p=0.068 and p=0.987, respectively.Conclusion MSI is likely an important biomarker for poor prognosis in patients with EEC, and this correlation is even more certain in patients with early-stage EEC.

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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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39 The oncologic outcome after fertility-sparing hormonal management more than 9 months treatment for early stage endometrioid endometrial cancer

10.1136/ijgc-2020-esgo.52 ◽

2020 ◽

Author(s):

Su Hyun Chae ◽

Seung-Hyuk Shim ◽

Sun Joo Lee

Keyword(s):

Endometrial Cancer ◽

Early Stage ◽

Oncologic Outcome ◽

Fertility Sparing ◽

Endometrioid Endometrial Cancer

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Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001039 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1379-1386 ◽

Cited By ~ 1

Author(s):

Rhonda Farrell ◽

Suzanne C. Dixon ◽

Jonathan Carter ◽

Penny M. Webb

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Adjuvant Treatment ◽

Cox Regression ◽

Early Stage ◽

Cox Regression Analysis ◽

Cancer Study ◽

Stage Ib ◽

Australian Cohort

ObjectiveThe role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity.Materials and MethodsFrom a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests.ResultsMedian follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001).ConclusionsIn this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

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