Early Endometrial Cancer Research Articles

Hypermethylated PCDHGB7 as a Biomarker for Early Detection of Endometrial Cancer in Endometrial Brush Samples and Cervical Scrapings.

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a “Tao brush”) and cervical scrapes (with a “Pap brush”) for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.

Estrogen Receptor- And Progesterone Receptor-Positive Thresholds in Predicting the Recurrence of Early Low-Risk Endometrial Cancer.

Background:Estrogen receptors (ER) and progesterone receptors (PR) have important prognostic value in endometrial cancer, but there is no recognized positive immunohistochemical threshold for predicting the recurrence of early low-risk endometrial cancer. The purpose of this study was to clarify the optimal positive thresholds of the immunohistochemical parameters the ER and PR in early low-risk endometrial cancer.Methods:A total of 332 patients with stage IA endometrial cancer were enrolled from the First Affiliated Hospital of Chongqing Medical University and People’s Hospital of Sha ping ba District in Chongqing between January 2013 and December 2018. First, univariate and multivariate Cox regression analyses were used to analyze the correlation between various clinical factors and the prognosis of early low-risk endometrial cancer. Then, the receiver operating characteristic curve (ROC curve) and Youden index were used to determine the positive thresholds of ER and PR.Results:The positive thresholds of ER and PR for predicting the recurrence of early low-risk endometrial cancer were 12% and 8%, respectively. Multivariate analysis showed that ER (P = 0.004), PR (P = 0.026), and p53 (P = 0.021) were risk factors for the prognosis of patients with early low-risk endometrial cancer. The recurrence-free survival and the overall survival in the low ER group and PR group were much lower than those in the high ER group and PR group (P < 0.001 of all).Conclusions:ER and PR positive thresholds of 12% and 8%, respectively, are the most suitable for predicting the recurrence of early low-risk endometrial cancer.

Metformin in Combination with Progesterone Improves the Pregnancy Rate for Patients with Early Endometrial Cancer.

Objective. To study the therapeutic effects of metformin in combination with medroxyprogesterone in the early endometrial cancer patients with fertility requirements. A total of 120 patients with early endometrial cancer admitted to and treated in our hospital were enrolled and evenly assigned into two groups according to different therapeutic regimens, namely, metformin group (metformin combined with medroxyprogesterone acetate) and control group (medroxyprogesterone acetate alone). The objective response rate (ORR) and disease control rate (DCR) were 71.7% (43/60) and 90.0% (54/60) in the metformin group and 53.3% (32/60) and 78.3% (47/60) in the control group, respectively. Adverse reactions such as gastrointestinal reaction, headache, and insomnia were mainly observed in patients. The body mass index (BMI) declined from (34.43 ± 4.34) kg/m2 to (24.77 ± 2.39) kg/m2 in the metformin group and from (33.37 ± 4.49) kg/m2 to (31.28 ± 3.55) kg/m2 in the control group after treatment. After treatment, serum levels of vascular endothelial growth factor (VEGF), angiotensin-2 (Ang-2), carbohydrate antigen 125 (CA125), and CA19-9 in the metformin group were significantly lower than those in the control group (P = 0.005, P < 0.001, P = 0.002, and P < 0.001). During follow-up, the pregnancy rate was 81.7% (49/60) in the metformin group and 61.7% (37/60) in the control group, and the former was prominently higher than the latter (P = 0.025). Metformin in combination with progesterone is effective in treating early endometrial cancer patients with fertility requirements, which significantly reduced the BMI of patients and increased the pregnancy rate after treatment.

Is Adjuvant Chemotherapy Necessary in Patients with Early Endometrial Cancer?

We investigated whether there was a difference in prognosis between patients with stage IA endometrial cancer with and without lymphovascular space invasion. We enrolled patients with stage IA (pT1aN0M0) endometrial cancer admitted to our hospital from 2009 to 2018. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy. We immunopathologically evaluated the presence or absence of lymphovascular space invasion in the tumor tissue using hematoxylin and eosin, Elastica-van Gieson, and podoplanin staining. We analyzed disease-free and overall survival and calculated patients' survival distribution using the Kaplan-Meier method and log-rank test. The multivariate analysis was performed to determine the prognostic factors. A total of 116 patients were included. The median age of the patients was 57 (range, 30-78) years, and the histological subtype revealed 98 and 18 cases of types 1 and 2, respectively. The median follow-up period was 71.9 (range, 10.8-149) months, and the 3-year disease-free and 3-year overall survival rates were 94% and 99%, respectively. The disease-free and overall survival rates were significantly shorter in type 2 patients than in type 1 patients (type 2 vs. type 1; 77% vs. 97%, P < 0.01, 94% vs. 100%, P = 0.014, respectively). The univariate and multivariate analyses showed that there were no significant differences in disease-free survival between the lymphovascular space invasion-positive and -negative groups among type 1 cases. There was no difference in prognosis between patients with stage IA and type 1 endometrial cancer with and without lymphovascular space invasion.

Contemporary Fertility-Sparing Management Options of Early Stage Endometrioid Endometrial Cancer in Young Nulliparous Patients.

Incidence of endometrial cancer (EC) has been increasing in recent years, especially in high-income countries. The disease commonly affects peri- and postmenopausal women; however, about 5% of women are diagnosed with EC in their reproductive age. Due to both the increasing incidence of EC among reproductive age women and trends to delayed childbearing, fertility-sparing treatment for young patients with EC has become extremely important for researchers and practitioners. Because the classic treatment with total hysterectomy and bilateral saplingo-oophorectomy is not an appropriate approach for young women demanding fertility preservation, several fertility-sparing options have been developed and summarized in this review. Utilization of different medications and their combination (progestagens, gonadotropin releasing hormones analogues, and metformin in different formulations) are tested and found as efficient for fertility-sparing treatment. New minimally invasive surgical techniques, combined with progestagens, are also confirmed as valuable. There are many novel conservative and surgical treatment approaches under investigation. Assuming that molecular biomarkers can be both diagnostic and prognostic to assist in prediction of response to a certain therapy, prognostic risk groups’ stratification along with specific biomarkers’ identification will ensure low recurrence and decrease mortality rates in young women with EC.

Maintenance Therapy Can Improve the Oncologic Prognosis and Obstetrical Outcome of Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer After Fertility-Preserving Treatment: A Multicenter Retrospective Study.

ObjectiveTo evaluate the effect of maintenance therapy for patients with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) after successful fertility-preserving management on prognosis and pregnancy outcome.MethodsWe performed a retrospectively analysis of 109 young women with atypical endometrial hyperplasia and early endometrioid endometrial cancer who had received complete response after fertility-preserving treatment at 5centers between May 2005 and March 2021. Maintenance therapy regimes included low-dose oral progesterone, levonorgestrel intrauterine device(LNG-IUD) and combination oral contraceptive (COC). The patients were divided into two groups, maintenance therapy group and non-maintenance therapy group. Clinical characteristics, treatment regimens, prognosis, and pregnancy outcome were compared between the two groups.ResultsThe overall disease recurrence rate of the maintenance therapy group was significantly lower than that of the non-maintenance therapy group (P < 0.001). The recurrence rate of atypical endometrial hyperplasia and endometrial cancer in the maintenance therapy group were significantly lower than those in the non-maintenance group (P < 0.001). Maintenance therapy can reduce pregnancy rates and live birth rates. Maintenance therapy can protect the endometrium in patients treated with assisted reproductive technology (ART), greatly reducing the recurrence rate after ART (P<0.001).ConclusionMaintenance therapy plays a very important protective role in fertility-preserving treatment for patients with atypical endometrial hyperplasia and endometrial cancer, which could significantly reduce the risk of recurrence. It is recommended that patients could receive maintenance therapy as long as possible during the period from achieving complete response to pregnancy preparation if possible. It may provide recurrence-free survival long enough for childless young women to prepare for pregnancy in the future. It can also protect the endometrium of those who are preparing to use assisted reproductive technology, possibly by reducing the risk of recurrence by excessive stimulation with assisted reproductive drugs.

A prospective comparison of costs between robotics, laparoscopy, and laparotomy in endometrial cancer among women with Class III obesity or higher

To compare the immediate operating room (OR), inpatient, and overall costs between three surgical modalities among women with endometrial cancer (EC) and Class III obesity or higher. A multicentre prospective observational study examined outcomes of women, with early stage EC, treated surgically. Resource use was collected for OR costs including OR time, equipment, and inpatient costs. Median OR, inpatient, and overall costs across surgical modalities were analyzed using an Independent-Samples Kruskal-Wallis Test among patients with BMI ≥ 40. Out of 520 women, 103 had a BMI ≥ 40. Among women with BMI ≥ 40: median OR costs were $4197.02 for laparotomy, $5524.63 for non-robotic assisted laparoscopy, and $7225.16 for robotic-assisted laparoscopy (p < 0.001) and median inpatient costs were $5584.28 for laparotomy, $3042.07 for non-robotic assisted laparoscopy, and $1794.51 for robotic-assisted laparoscopy (p < 0.001). There were no statistically significant differences in the median overall costs: $10 291.50 for laparotomy, $8412.63 for non-robotic assisted laparoscopy, and $9002.48 for robotic-assisted laparoscopy (p = 0.185). There was no difference in overall costs between the three surgical modalities in patient with BMI ≥ 40. Given the similar costs, any form of minimally invasive surgery should be promoted in this population.

Dusp6 immunohistochemistry is associated with the response of atypical endometrial hyperplasia and early endometrial cancer to conservative treatment.

Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment.However, its predictive accuracyhas never been calculated. We aimed to define it in conservatively treated AEH and EEC. All patients <45years with AEH or EEC and conservatively treated with hysteroscopic resection+LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve. Thirty-six women were included.Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR=16 (P=0.0074);predictive accuracy analysis showed sensitivity=80%, specificity=90%, PPV=57.1%, NPV=96.4%, AUC=0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR=0.4; P=0.53). Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy.

Introduction of gasless laparoscopic surgery as a minimally invasive procedure for endometrial cancer and its usefulness from the viewpoint of the learning curve

BackgroundWe investigated the usefulness of gasless laparoscopic surgery (GLS) using a subcutaneous abdominal wall lifting method for endometrial cancer.MethodsWe studied 105 patients with early endometrial cancer who underwent GLS (55) or open surgery (50). A uterine manipulator was used in all GLS cases. We compared operative time, blood loss, number of lymph nodes removed, hospital stay, perioperative complications, cases converted to laparotomy, and recurrence and survival rates. We also studied the learning curve and proficiency of GLS.ResultsThe GLS group had significantly longer operative time (265 vs. 191 min), reduced blood loss (184 vs. 425 mL), shorter hospital stay (9.9 vs. 17.6 days), and fewer postoperative complications (1.8 vs. 12.0%) than the open group. No case was converted to laparotomy. Disease-free and overall survival rates at 4 years postoperatively (GLS vs. open groups) were 98.0 versus 97.8 and 100 versus 95.7%, respectively, and there was no significant difference between the groups. Regarding the learning curve for GLS, two different phases were observed in approximately 10 cases. Operator 2, who was not accustomed to laparoscopic surgery, showed a significant reduction in operative time in the later phase 2.ConclusionsGLS for endometrial cancer results in less bleeding, shorter hospital stay, and fewer complications than open surgery. Recurrence and survival rates were not significantly different from those of open surgery. This technique may be introduced in a short time for operators who are skilled at open surgery but not used to laparoscopic surgery.

Insulin Resistance and Metabolic Syndrome Increase the Risk of Relapse For Fertility Preserving Treatment in Atypical Endometrial Hyperplasia and Early Endometrial Cancer Patients.

ObjectiveFertility-sparing treatment for young women with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) is a difficult challenge. Insulin resistance (IR) and metabolic syndrome (MetS) are two potentially crucial, but currently enigmatic factors in the recurrence of AEH and early EC patients. In this study we attempt to elucidate these factors.MethodsA retrospective study was conducted from January 2010 to December 2019. Risk factors for recurrence and complete remission time after recurrence (RCR time) were investigated. ROC curves were built to estimate the accuracy of the metabolic characteristics and Kaplan–Meier (K–M) analysis was used to calculate recurrence-free survival (RFS) for patients with various IR or MetS statuses.ResultsA total of 111 AEH or early EC patients met the criteria and were enrolled in our study. Univariate analysis found that BMI ≥25 kg/m2 (OR = 2.7, 95% CI: 1.1–6.4, P = 0.03), IR (OR = 9.5, 95% CI: 3.3–27.0, P <0.001), MetS (OR = 4.9, 95% CI:1.5–15.5, P = 0.008), IR+ and MetS+ (OR = 21.0, 95% CI: 4.8–92.7, P <0.001), histological type (OR = 3.5, 95% CI: 1.5–7.9, P = 0.003), and maintenance treatment (OR = 0.3, 95% CI: 0.1–0.6, P = 0.005) were all significantly associated with recurrence and longer RCR time. Among these factors, IR and MetS were determined to be two independent risk factors for recurrence. Moreover, using IR and MetS as markers significantly improved the diagnostic accuracy of recurrence for fertility-sparing treatment patients (AUC = 0.818, P <0.05) and may play synergistic roles in suppressing treatment. K–M analysis indicated both metabolic features played important roles in RFS (P <0.05).ConclusionBoth IR and MetS were significantly associated with recurrence and longer RCR time in AEH and early EC patients receiving fertility-sparing treatment.

Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis

ObjectiveProgestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus...

Patterns of Practice for Adjuvant Treatment of FIGO 1B Grade 3 Endometrial Adenocarcinoma Following Publication of ASTRO 2014 Guidelines for Postoperative Treatment in Women With Early Stage High Risk Endometrial Cancer

In 2014, the American Society for Radiation Oncology (ASTRO) published evidence-based guidelines for the role of postoperative radiation therapy in endometrial cancer. These guidelines were also endorsed by the Society of Gynecologic Oncology (SGO). They strongly recommended that women with grade 3 endometrioid endometrial cancer with deep myometrial invasion) receive pelvic radiation (EBRT) and not vaginal cuff brachytherapy (VCBT) given their increased risk of pelvic recurrence based on high quality evidence. We analyzed patterns of practice before and after this consensus guideline was published.We queried the National Cancer Database to identify all women with either FIGO 1C grade 3 disease from 2004-2009 and FIGO 1B grade 3 disease from 2009-2017 with endometrioid histology who were treated surgically. Patients were then stratified to treatment between 2004-2014 (prior to ASTRO guideline updates) and 2015-2017. Patients were excluded from final analysis if they were metastatic at diagnosis, received palliative-intent radiation, treatment parameters were unknown, or age < 18. Multivariable logistic regression was performed to evaluate for factors associated with receipt of VCBT using clinical and sociodemographic covariates.We identified 6,792 patients with grade 3 endometrioid endometrial carcinoma meeting current FIGO 1B disease classification, diagnosed between 2004 and 2017. Adjuvant radiation was not delivered to 38% of patients identified in the study period, and 26% received both EBRT and VCBT. From 2004-2014, of the patients that received single modality adjuvant radiation, 1168 patients received VCBT only (56%) and 908 received EBRT only (44%). The corresponding numbers for 2015 to 2017 for VCBT and EBRT were 347 (62%) and 217 (38%), respectively. The increase in VCBT utilization in 2015-2017 was statistically significant (P = 0.025). Patients who received VCBT were more likely to receive chemotherapy, be treated at a community cancer center or academic cancer center, or live within 50 miles of the treatment center (all P < 0.01). Racial and sociodemographic factors were not associated with likelihood of receipt of VCBT.Based on ASTRO 2014 guidelines, EBRT is strongly recommended in patients with FIGO 1B/ grade 3 endometrioid endometrial carcinoma. However, the rate of EBRT paradoxically declined in the period after the publication of the guideline. This may be in part due to conflicting data from ongoing trials during that time such as GOG 249 and PORTEC 3. Further investigation is warranted to investigate reasons for these variations in practice.C. Weil: None. F. Lew: None. D.K. Gaffney: Research Grant; NCI. Consultant; NCI. run meetings; NCI.G. Suneja: Research Grant; National Institutes of Health. Honoraria; National Comprehensive Cancer Network. Travel Expenses; National Comprehensive Cancer Network, Radiation Oncology Institute, American Board of Radiology; Radiation Oncology Institute, National Comprehensive Cancer Network, ASTRO.V.M. Williams: Involved in planning the mission and activities for the subcommittee; ARRO Equity and Inclusion Subcommittee.

Innovative Protocol of ART in Women with LNG-Ius for Fertility-Sparing Treatment of Endometrial Intraepithelial Neoplasia

<h3>Study Objective</h3> to evaluate the safety and efficacy of an Assisted Reproductive Technology (ART) program based on controlled ovarian stimulation with Levonorgestrel Intrauterine System (LNG-IUS) <i>in situ</i> in women affected by endometrial intraepithelial neoplasia<i>.</i> <h3>Design</h3> prospective observational study. <h3>Setting</h3> young women conservatively treated for FIGO IA G1 early endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) who underwent ART program with LNG-IUS <i>in situ</i>. <h3>Patients or Participants</h3> 6 patients undergoing conservative treatment for EEC (n=1) or AEH (n=5), from January 2019 to March 2021. <h3>Interventions</h3> patients with focal EEC were treated by hysteroscopic resection of the lesion according to Mazzon's technique; patients with AEH were treated by superficial endometrial resection preserving the basal layer of the endometrium. LNG-IUD was inserted in all patients after surgery. Patients were followed with histological evaluation at 3 months by endometrial biopsy, until two subsequent negative biopsies were obtained. At this time, controlled ovarian stimulation was started, oocytes retrieval was performed, and mature oocytes were cryopreserved. After removal of LNG-IUS, embryo transfer procedure was performed. Rates of oocytes retrieved, mature frozen oocytes and pregnancies were assessed. Rates of response and recurrence were also evaluated <h3>Measurements and Main Results</h3> out of 6 patients, 100% had a complete response and no subsequent relapse. Oocytes retrieved were 9.33±2.28 (mean±SD); mature oocytes were 7.5±1.89 (mean±SD). Embryo transfer was performed three months after the LNG-IUS removal. 4 pregnancies were obtained (66.67%),2(50%) of whom resulted in live birth, 1(25%) is still ongoing, 1(25%) resulted in a miscarriage in the first trimester. 2 patients (33.33%) experimented implantation failure and they are waiting for a further attempt <h3>Conclusion</h3> the presence of LNG-IUS during controlled ovarian stimulation has no detrimental effects on ovarian quality, while allowing to balance the potentially dangerous effect of hyperestrogenism on the endometrium of patients affected by AEH or EEC, with promising results about pregnancy outcomes.

Hysteroscopic Resection and Laparoscopy in Fertility-Sparing Surgery for Early Endometrial Cancer and Complex Atypical Hyperplasia: A Single Institutional Experience

背景及目的：分析使用黃體激素治療前以子宮鏡及或腹腔鏡處理早期子宮內膜癌（EC）或複雜非典型增生（CAH）的患者的腫瘤預後和生育的結果。方法：分析在使用黃體激素治療之前曾接受子宮鏡及或腹腔鏡進行骨盆腔評估的早期子宮內膜樣腺癌或複雜性非典型增生的婦女。術後六個月評估其疾病緩解率，並在分析其受孕率。結果：6例早期子宮內膜癌患者和3例複雜非典型增生患者在開始黃體激素治療之前接受了手術治療。完全緩解率為77%（複雜非典型增生為100%，子宮內膜癌為66%），其中有兩名患者在治療6個月後疾病依然存在。平均追蹤23個月（8-124個月）後，沒有患者有復發現象。在欲懷孕婦女當中，活產率為60%。在那些原本疾病完全緩解的病人當中，有三位於平均24個月內復發。結論：使用子宮鏡及或腹腔鏡癌症分期處理早期子宮內膜癌可得到較準確的癌症分期及創造良好的受孕環境，也不影響患者的癌症預後及活產率。

A Pilot Study for the Validation of Sentinel Lymph Node Biopsy with Indocyanine Green Fluorescence Method in Early Endometrial Cancer at Fundacion Jimenez Diaz University Hospital

Background: Sentinel Lymph Node Biopsy is a technique developed to predict lymphatic involvement in patients with early endometrial cancer, decreasing the morbimortality associated with routine systematic lymphadenectomy and improving quality of life. Main Objective: To determine the detection rate and negative predictive value of the Sentinel Lymph Node Biopsy by Immunofluorescence in patients with early endometrial cancer. Methods: A descriptive observational study in patients with early endometrial cancer (FIGO stage I-II) for all histological types and grades, who underwent the Sentinel Lymph Node by immunofluorescence Technique, between June 2019 and March 2020 at the Fundación Jiménez Díaz University Hospital. We used indocyanine green powder for injection, with a concentration of 25 milligrams (mg). We proceeded to dissolve it in 10 cubic centimeters (cc) of distilled water to. After which, we injected 2 cc of the prepared solution into the cervix at the 3 and 9 o’clock positions at a depth of 1 centimeter. Results: Eighteen patients were included, analysing a total of 26 sentinel nodes: 24 pelvic and 2 paraortic; and a total of 273 lymph nodes (sentinel and non-sentinel nodes): 83 right pelvic, 86 left pelvic and 104 paraortic. All nodes were negative for metastasis. Global and bilateral detection rates were 77.78% and 50% respectively. The Negative Predictive Value and sensitivity were 100%. No significant difference in morbimortality was found between performing only Sentinel Lymph Node technique or systematic lymphadenectomy, but the association with quality of life was significant, with better results for those who only underwent the sentinel lymph node technique versus systematic lymphadenectomy (0% vs 77%). Conclusion: The global and bilateral detection rates of the Sentinel Lymph Node Technique by immunofluorescence were 77.78% and 50% respectively, obtaining a Negative Predictive Value and Sensitivity of 100%. Sentinel Node Biopsy is a valid technique to predict lymphatic affectation in early endometrial cancer, with lower morbimortality than systematic lymphadenectomy.

Impact of lymphadenectomy and lymphoedema on health-related quality of life 1 year after surgery for endometrial cancer. A prospective longitudinal multicentre study.

To assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health-related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC). Prospective longitudinal cohort multicentre study. Departments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden. Two-hundred-and-thirty-five women with early stage EC were included; 116 with high-risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low-risk EC had surgery without lymphadenectomy (-LA). The generic SF-36 and EQ-5D-3L and the lymphoedema-specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient-reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4-6 weeks, 6 months and 1 year postoperatively. HRQoL scores. No significant differences were seen in HRQoL between the +LA and -LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL. Lymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema-specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL. Lymphoedema has impact on lymphoedema-specific, but not on generic, HRQoL, 1 year after surgery for EC.

Fallo del mapeo linfático gammagráfico en el cáncer endometrial. Causas y soluciones

AimTo evaluate the effect of technical problems and patient characteristics on sentinel lymph node (SLN) scintigraphic detection and mapping success in early stages of endometrial cancer (EC). MethodsPatients with clinical early stage EC (IA-IB) underwent SLN mapping using technetium-99m-nanocolloid,between September 2011 and February 2020. were included. There were excluded cases with technical problems, 92 patients were included for the analysis of the diagnostic performance and the relation of mapping failure (pelvic unilateral or not detected SLN) with patient (age, body mass index, previous pelvic disease or surgery) and disease characteristics (histology, grade, myometrial invasion, lymphovascular space infiltration, tumor size, and lymphatic infiltration risk). ResultsThe overall detection rate was 79%. Lymph node metastases were diagnosed in 7 patients. Age (p=0.01), depth of myometrial invasion ≥ 50% (p=0.04) and high risk of lymphatic infiltration (p=0.02) were positively associated with mapping failure. In multivariate analysis, age was significantly associated with mapping failure [odds ratio=1.63, 95%CI: 1.06-2.50; p=0.027]. ConclusionsAge, depth of myometrial invasion and high risk of lymphatic infiltration were the factors associated with higher mapping failure. An individualized injection technique, optimizing the methodology, could minimize the detection failures.

Patient-initiated follow-up of early endometrial cancer: a potential to improve post-treatment cardiovascular risk?

PurposeIs patient-initiated follow-up, post-surgical treatment of early endometrial cancer safe and can it be used holistically to improve cardiovascular health? What are the cost implications of this model of follow-up?MethodsRetrospective data of 98 patients discharged to patient-initiated scheme since 2012. Service evaluation by anonymous patient feedback including physical health effects of the programme including weight loss. Financial cost was compared to traditional hospital-based follow-up over five years.ResultsNo evidence of recurrence over 54 months median follow-up in low-risk endometrioid endometrial cancer. Patient feedback indicates that the exercise course helped women reduce their BMI. Over one third women felt happier and one fifth felt more confident and had a better ability to cope with stress. Total of 91% patients would recommend this model of follow-up to friends or family in the same circumstance. European Society for Medical Oncology guidance suggests the number of hospital-based follow-up appointments required for this cohort would cost £109,760. Calculations in this paper examine the cost of patient-initiated follow-up and reflect an overall saving of around 96.5%.ConclusionThis service evaluation supports the claim that patient-initiated follow-up represents a safe alternative to the traditional hospital-based protocol. There is a potential for additional services to be offered to encourage and promote a healthy lifestyle linked to improving quality of life and cardiovascular survival following surgery for endometrial cancer.Implications for cancer survivorsCardiovascular morbidity is the most common cause of death in endometrial cancer survivors. Incorporating an exercise course as part of routine follow-up can help reduce this risk. The friendships formed by this communal follow-up can contribute towards emotional health and recovery. This holistic approach should be incorporated into novel follow-up strategies to help reduce patient BMI and reduce cardiovascular risk.

Defining optimal adjuvant treatment for high-risk early-stage endometrial cancer

<h3>Objectives:</h3> There is a paucity of data to determine the optimal adjuvant treatment of early-stage, high-risk endometrial histologies. While many retrospective series focus on uterine serous cancer, the optimal treament for other high risk subtypes, including G3 endometrioid cancer, clear cell carcinoma or carcinosarcoma is not yet clear. We sought to determine patterns and outcomes of adjuvant treatment for early-stage high-risk endometrial cancers of multiple histologic subtypes. <h3>Methods:</h3> After Institutional Review Board approval, a retrospective review of patients at Montefiore Medical Center diagnosed with early stage high-risk endometrial cancer between 2006 and 2018 was conducted. Inclusion criteria included: 1) Stage I-II disease 2) Grade 3 endometrioid, carcinosarcoma, clear cell, serous, or mixed histologies. Demographic and clinical information pertaining to cancer treatment was collected. The primary outcome was recurrence-free survival. Univariate and multivariate analyses were performed and a Kaplan-Meier progression free survival curve was created using STATA 14.2. P-value <0.05 was considered statistically significant. <h3>Results:</h3> A total of 1208 patients with endometrial cancer were identified, 249 of which met inclusion criteria. Sixty-percent (149) of patients had serous, clear cell, or mixed histologies, 17% (43) had carcinosarcoma, 23% (57) had Grade 3 endometrioid histology. Most patients received adjuvant combination chemoradiotherapy (52%, N=131) whereas 20% (49) received radiation alone (brachytherapy or external beam), 7% (18) received chemotherapy alone, and 20% (50) received no adjuvant treatment. Of the 48 (19%) disease recurrences, 25 (45%) were distant metastases at the time of recurrence. Combined chemoradiotherapy was associated with increased recurrence-free survival compared with chemotherapy alone (p=0.026) or radiation alone (p=0.004). Compared to G3 endometrioid histology, the hazard ratios for recurrence were: 3.70 (CI 1.31-10.41, p=0.01) for serous histology, 1.37 (CI 0.15-12.21, p=0.78) for clear cell, 9.70 (CI 3.22-29.16, p<0.01) for carcinosarcoma, and 4.59 (CI 1.28-16.46, p=0.02) for mixed histology. Charlson Cormorbidity Index was also associated with cancer recurrence (HR 1.53, CI 1.28-1.82, p<0.01), as was age (HR 0.95, CI 0.92-0.99, p=0.01). <h3>Conclusions:</h3> Multimodal treatment with chemotherapy and radiation therapy is associated with increased recurrence free survival in patients with high-risk early-stage endometrial cancers, in comparison to radiation or chemotherapy alone after surgical staging. Histologic subtype, comorbid conditions, and age all significantly impact survival. Notably, recurrence in clear cell tumors were not significantly impacted by adjuvant treatment with chemotherapy and radiation therapy. Randomized trials are needed to determine the optimal treatment of high-risk histologic subtypes.

Analysis of Factors Related to Lymph Node Metastasis in Early-Stage Type 1 Endometrial Cancer: Verifying the Clinical Value of Positive Threshold of the Immunohistochemical Parameter Ki67.

ObjectiveLymph node metastasis (LNM) is an important reference indicator for the prognosis of endometrial cancer (EC). Even in patients with early low-risk EC, many people still have LNM. The purpose of this study was to investigate the related factors influencing LNM in early-stage EC and determine the optimal positive threshold of immunohistochemical parameter Ki67 for predicting LNM, providing auxiliary reference indicators for clinical diagnosis and treatment.MethodsThe clinicopathological data of 651 patients with “apparent” early-stage EC who underwent standard surgical treatment were included. Univariate and multivariate logistics regression were used to analyze the correlation between each clinicopathological factor and LNM. Receiver operating characteristic curve (ROC curve) and Youden index were used to determine the optimal positive threshold of Ki67 for predicting LNM. Finally, correlation between Ki67 and various clinicopathological factors was analyzed, and the predictive value of each prognostic factor was compared.ResultsMultivariate analysis found that histologic grade (P=0.023), lymphatic vessel space invasion (LVSI) (P < 0.001), serological index Ca125 (P=0.002), immunohistochemical parameter Ki67 (P < 0.001), ER (P < 0.001) and P53 (P=0.001) were independent prognostic factors of LNM. ROC curve and Youden index showed that the optimal positive thresholds of Ki67 to predict LNM were 40%. Based on this, ROC curve showed that the area under the curve (AUC) of Ki67 (AUC=0.714) was larger than other single predictors, and Ki67 combined with other predictors can significantly increase the AUC value (AUC= 0.847 and 0.868, respectively).ConclusionKi67 was an important predictor for predicting the LNM in early-stage EC and taking a positive percentage of about 40% can be used as the positive threshold of the immunohistochemical parameter Ki67. On this basis, Ki67 combined with other predictive indicators can significantly improve prediction performance and can be used for segmentally predicting LNM of early-stage EC.