Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Fertility preservation in patients with gynecologic cancer

In this editorial we comment on the article by Gu et al.We focus and debate the necessity of fertility sparing surgery in young women’s with gynecologic cancers,specifically on those patients with the desire to conceive.This type of individu-alized treatment options is often very difficult,due to the risk of disease evolution and multiple disparities in fertility preservation services among women in di-fferent countries and societies.For this reason national policy interventions are mandatory in order to ensure equitable access this procedures,in women with cancer.

Superiority of indocyanine green-enhanced near-infrared fluorescence-guided imaging for laparoscopic lymph node dissection in patients with early-stage endometrial cancer: A retrospective cohort study

Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complications.This study aimed to explore whether indocyanine green(ICG)-enhanced nearinfrared(NIR)fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma.Methods:In this retrospective study,we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine between January 2019 and January 2021.Depending on whether ICG-enhanced NIR fluorescence guidance was used,the patients were assigned to the ICG group or non-ICG group.Patients were followed-up for one year after surgery.Data on demographic characteristics,pathological results,operative outcomes,and complications were collected and analyzed.Results:The baseline characteristics were comparable between the ICG group and non-ICG group,including age,BMI,pregnancy history,and preoperative hemoglobin.For surgical outcomes,the patients in ICG group had significantly lower intraoperative blood loss(50 mL vs.120 mL,p<0.001),less postoperative pelvic drainage time(4.14±1.44 d vs.5.70±1.89 d,p¼0.001),shorter duration of hospital stay(5.26±1.41 d vs.7.37±1.85 d,p¼0.003),higher number of positive pelvic lymph nodes(PLNs)(1 vs.0,p¼0.003),and more PLN-positive cases(16.0%vs.3.6%,p¼0.003)than the patients in non-ICG group.However,no significant differences were noted in blood transfusion requirement,operative time,hemoglobin level decreases,number of PLNs harvested,or the presence of lymphocysts between the two groups.Conclusion:Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.

Synchronous endometrial and ovarian cancer: A case report

BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer(EC)or OC.In this review we present 2 cases of women who were diagnosed with SEOC,and discuss the clinical characteristic of SEOC,diagnostic and molecular profiling issues.Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples.CASE SUMMARY In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC.They underwent surgical treatment and staging.Next-generation sequencing of 10 gene-panel identified CTNNB1,PIK3CA,and PTEN gene mutations in ovarian tissue in one case,while none of these genes were mutated in other case.Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage.CONCLUSION Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.

Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background:LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers.Nevertheless,the impacts of DLX6-AS1 on endometrial cancer(EC)development remained obscure.The study explored the influence of DLX6-AS1 on EC progression via the microRNA(miR)-374a-3p/zinc-finger protein(ZFX)axis.Methods:EC cell lines were collected and DLX6-AS1,miR-374a-3p,and ZFX levels in EC cell lines were detected.The EC cells were transfected with DLX6-AS1,miR-374a-3p,and ZFX constructs to examine the biological functions of EC cells.The xenograft model was established for detecting tumor growth.Rescue experiments were conducted to verify the interaction of DLX6-AS1,miR-374a-3p,and ZFX in EC cells.Results:DLX6-AS1 and ZFX levels were elevated,while miR-374a-3p exhibited a reduced level in EC cells.Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells.Reduced DLX6-AS1 repressed tumor development.MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing,while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth.Mechanically,DLX6-AS1 was found to bind to miR-374a-3p,and miR-374a-3p targeted ZFX.Conclusion:DLX6-AS1 depletion restricts the malignant phenotype of EC cells.The study might provide novel therapeutic biomarkers for EC treatment.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis

BACKGROUND Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide,and early-stage high-risk endometrial cancer has a poor prognosis.Adjuvant treatments after surgery,such as chemotherapy and radiotherapy,have been widely used in clinical practice to improve patient survival.Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer.However,its efficacy,safety,and longterm prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial.Therefore,this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with earlystage high-risk endometrial cancer and evaluate its safety.AIM To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety.METHODS We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022.The control group(100 patients)underwent conventional surgical treatment,and the study group(100 patients)was administered adjuvant medroxyprogesterone acetate tablets on top of the control group.The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients.The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer.RESULTS According to the Cox regression analysis,age[hazard ratio(HR)=4.636,95%confidence interval(95%CI):1.411-15.237],pathological type(HR=6.943,95%CI:2.299-20.977),molecular typing(HR=5.789,95%CI:3.305-10.141),and myometrial infiltration(HR=5.768,95%CI:1.898-17.520)were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer.CONCLUSION Age,pathological type,molecular typing,and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer.The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

Laparoscopic versus laparotomy approach to endometrial cancer: A prospective study

Objective: The aim of this study was to compare laparoscopic (LPS) and laparotomy (LPT) approaches for endometrial cancer, and to assess intraoperative and postoperative results, disease-free survival and overall survival. Methods: We designed a prospective observational study, every patient diagnosed of endometrial cancer and subsidiary to surgical staging was included. Total hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy were performed in every case. Paraaortic lymphadenectomy was performed depending on tumor histology. Results: 70 patients with endometrial cancer were enrolled, 49 (70%) were treated laparoscopically and 21 (30%) laparotomically. There was not statistical significant difference in the mean operative time, it was 183.06 ± 21.03 min (range 120 - 230) in the LPS group and 195.24 ± 28.39 min (range 130 - 240) in the LPT group, mean difference 12.16 (95% CI ﹣0.2 - 24). There was no difference in the number of lymph nodes resected. Mean blood loss was lower in the LPS group. There were less postoperative complications, 3 (6.12%) in the LPS group and 7 (33.3%) in the LPT group (p Conclusion: Laparoscopic approach for endometrial cancer offers similar results in terms of survival and oncological radicality as the laparotomic approach and a lower rate of complications, a quicker convalescence time and a shorter hospital stay.

Treatment Results of Adjuvant Brachytherapy as Monotherapy in Endometrial Cancer: A Retrospective Study from Faculty of Medicine, Chiang Mai University

Purpose: To report the retrospective study of using intravaginal brachytherapy as adjuvant monotherapy for endometrial cancer. Materials and Methods: From 2001-2009, 47 patients who received completely surgical staging for endometrial carcinoma and were designed by multidisciplinary team were enrolled. All patients received intravaginal brachytherapy (IVBT) with the dose of 5.5 - 7 Gy in 2 - 6 fractions. The treatment results and late toxicities were evaluated and recorded. Results: At the median follow-up time of 44 months, the local control, disease-free survival, metastasis-free survival and overall survival rates were 100%, 97.9%, 97.9% and, 97.9%, respectively. Only age showed the statistical significance with the p-value of 0.046. Two patients (4.3%) developed late genitourinary toxicity. Conclusion: The using of adjuvant IVBT as monotherapy for endometrial carcinoma is feasible.

Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer:Clinical and pathological perspectives

Endometrial cancer is the most common gynecological cancer in developed countries,and its incidence has increased.The majority of patients with endometrial cancer have an early disease and favorable prognosis;however,a significant proportion of endometrial cancer,which mainly comprises high-grade or type II endometrial cancer such as serous,clear cell,and carcinosarcoma,shows advanced/recurrent disease and dismal prognosis.Novel therapeutic development is required for patients with aggressive endometrial cancers.Recent genomic and immunohistochemical analyses revealed human epidermal growth factor receptor 2(HER2)overexpression/gene amplification in 20%-40%of patients with type II endometrial cancer.Historically,HER2 targeted therapy has been developed for various major cancers,including breast and gastric cancer.Notably,recent advances in HER2 targeted therapy for patients with type II endometrial cancer are also expected to change.Simultaneously,an optimized HER2 test for endometrial cancer as companion diagnostics should be established.In this review,we summarize the recent findings on endometrial cancer,current treatment,optimized HER2 testing,key clinical trials on HER2 targeted therapy,and future directions in aggressive endometrial cancer,including serous carcinoma and carcinosarcoma.

Long term outcome and quality of life after pelvic exenteration for recurrent endometrial and cervical cancers

Introduction: Pelvic exenteration can cure recurrent gynecological malignancies. However, treatment morbidity is over 50% in radiated pelves. We evaluated the outcome, the morbidity and the quality of life after exenteration. Methods: Patients who underwent an exenteration for recurrent cervical or endometrial cancer in our institution between 1999 and 2011 were retrieved. Survival rates were calculated according to Kaplan-Meier method and compared using the logrank test. The EORTC QLQ-C30 and QLQ-CX24 questionnaires were sent to patients alive in January 2012. Results: We identified 25 patients: 17 (68%) had cervical cancer and 8 (32%) endometrial cancer. 92% of them had received radiotherapy previously. All patients had a central pelvic recurrence, within a median time of 30 months [4 - 384] from initial treatment. Early complications requiring a re-laparotomy occurred in 9 patients (36%). Late complications included 2 (8%) fistulas, 2 (8%) occlusion and 1 (4%) ureteral stenosis. Complete resection was obtained in 92% of patients. Disease Free and Overall survival rates were better in cervical rather than in endometrial cancer (median DFS in months 17 [2 - 145] vs 9.5 [3 - 21], p = 0.064, median OS in months 20 [2 - 145] vs 13 [4 - 42], p = 0.019). 69% of patients answered the quality of life questionnaires. Mean global quality of life score was 45 on a scale of 0 - 100, none of the patients had a sexual activity. Conclusions: Morbidity of exenteration remains high and quality of life is altered. Endometrial cancer is associated with a poorer prognosis. In those patients, exenteration should be put in balance with best supportive care.

Usefulness of Immuno-Magnetic Beads Conjugated with Anti-EpCAM Antibody for Detecting Endometrial Cancer Cells

A simple and non-invasive method for detecting endometrial cancer in women with abnormal uterine bleeding is required. For this purpose, we prepared immuno-magnetic beads conjugated with anti-human EpCAM rat monoclonal antibody (mAb) for isolating exfoliated endometrial cells including endometrial cancer cells in vaginal discharge. The affinities of the anti-human EpCAM rat mAbs were analyzed by flow cytometry and immunocytochemistry and then magnetic beads were conjugated with the mAbs. The rate of retrieval of endometrial cells using the immuno-magnetic beads was calculated. Endometrial cells were isolated using the immuno-magnetic beads from the vaginal discharges of 22 patients with endometrial cancer and 16 non-malignant controls. The isolated cells were stained using endometrial cancer specific-mAbs and analyzed by flow cytometry and imaging cytometry. The immuno-magnetic beads conjugated with high-affinity mAb (clone 1456) appeared to have very low auto-fluorescence. Sufficient enrichment of Ep-CAMpositive cells using immuno-magnetic beads was observed in both simulation and clinical samples. The overall sensitivities of flow cytometry and imaging cytometry to detect endometrial cancer cells were 72.7% and 45.5%, respectively. Meanwhile, the overall specificities of flow cytometry and imaging cytometry for healthy controls were 75.0% and 81.3%, respectively. Our immuno-magnetic beads have very low auto-fluorescence, so they could be useful for fluorescent analysis, such as fluorescent immunochemical staining. In the future, these novel immuno-magnetic beads could be used for cytological study.

Adjuvant External Beam Radiotherapy ±Brachytherapy in Endometrial Cancer: A Retrospective Study from Faculty of Medicine, Chiang Mai University

Purpose: To report the retrospective study of external beam radiotherapy (EBRT) ± intravaginal brachytherapy (IVBT) as adjuvant treatment for endometrial cancer. Materials and Methods: From 2001-2009, 152 patients received complete surgical staging for endometrial carcinoma and were designed by a multidisciplinary team to receive EBRT ± IVBT. The treatment results and late toxicities were evaluated and recorded. Results: At the median follow-up time of 43 months, the disease-free survival, metastasis-free survival and overall survival rates were 96.9%, 96.9% and 96.9%, respectively. Stage and age showed the statistical significance with the p-value of less than 0.001. From five to ten percent of patients developed Grades 1-2 late gastrointestinal and genitourinary toxicities, respectively. Conclusion: The using of adjuvant EBRT ± IVBT for endometrial?carcinoma yielded treatment results and acceptable toxicities.

ErbB Receptors and ErbB Targeted Therapies in Endometrial Cancer

The Epidermal Growth Factor system is present in human organs and plays an important role in cell proliferation, differentiation and apoptosis during embryogenesis and postnatal development. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands. Dysregulation of the Epidermal Growth Factor signaling network is implicated in the pathogenesis of various disorders. Especially in cancer, the Epidermal Growth Factor system becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). EGFR overexpression may have a dual role in endometrial cancer. It seems that in type I endometrial cancer, EGFR overexpression did not affect disease progression. However in type II endometrial cancer, EGFR overexpression associated with high grade disease and adverse clinical outcome. Moreover ΕrbB-2 overexpression especially in type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival. The potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for cancer therapy has been investigated for over 20 years. There are 2 major classes of ErbB targeted therapies: anti-ErbB monoclonal antibodies (MoAbs) and ErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have still shown modest effect in unselected endometrial cancer patients. However, they may be clinically active as adjuvant therapy in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.

Successful robot-assisted surgery for treating endometrial cancer affecting bicornuate-bicollis or didelphic uterus

Uterine anomalies are mainly associated with improper development of Mullerian ducts. To our knowledge, reports describing the use of a da Vinci Robot System for treating an endometrial cancer in a woman with an abnormal uterus are lacking. Here, we reported the description of two extremely obese women, affected by endometrial cancer and presenting bicornuate-bicollis and didelphic uterus have been treated by Robot System-assisted surgery. No operative and postoperative complications were recorded. Both women are disease-free to follow-up. A robot-assisted surgery could represent an effective treatment option for complex hysterectomies and in complicated patients, as those showing an extreme obesity.

Isolated Para-Aortic Nodal Recurrence in Endometrial Cancer

Aim: While cytoreductive surgery should be considered for patients with regional recurrence of endometrial cancer, the management of isolated para-aortic lymph node recurrence remains controversial. We investigated the frequency of isolated recurrence in the para-aortic lymph nodes and the effectiveness of surgery for such recurrence. Methods: A retrospectively maintained endometrial cancer database at the Cancer Institute Hospital in Japan was reviewed to identify sites of metastasis and recurrence. Results: A total of 2322 patients with endometrial cancer underwent primary treatment with systemic lymphadenectomy between 1984 and 2015. Systematic pelvic and para-aortic lymph node dissection was performed in 889 patients (Group 1), while 1433 patients underwent dissection of only the pelvic lymph nodes (Group 2). Although 16 patients (1.1%) in Group 2 had isolated para-aortic recurrences, only 3 patients (0.3%) in Group 1 had documented recurrences in the para-aortic lymph nodes (p = 0.043). Although second recurrence occurred in 30.0% of patients who underwent surgical recurrence treatment, second recurrence occurred in 77.8% of patients who underwent non-surgical recurrence treatment (p = 0.037). In addition, the overall survival rate for patients who underwent surgical recurrence treatment (80.0%) was significantly higher than that for patients who underwent non-surgical recurrence treatment (33.3%) (p = 0.026). Conclusions: Patients who underwent dissection of only the pelvic lymph nodes had a higher frequency of isolated recurrence in the para-aortic lymph nodes. In addition, a relatively good prognosis could be achieved with surgical treatment for isolated recurrence in the para-aortic lymph nodes, which was better than that achieved using non-surgical methods.

Real-time co-registered photoacoustic and ultrasonic imaging for early endometrial cancer detection driven by cylindrical diffuser

In illuminating tissues,a cylindrical diffuser(CD)has an advantage over regular laser sources due to its ability to illuminate a larger volume of the target tissue.This paper presents a co-registered large volume photoacoustic(PA)and ultrasonic(US)imaging for early endometrial cancer(EEC)detection using CD.It has the advantage that the US imaging system is outside the body and only the PA excitation device is inside the body,which makes the system more efficient and less invasive for EEC detection.The paper reports on two sets of experiments.Thefirst set produced real-time PA images of blood vessel phantom.The second set demonstrated the imaging of pig uterus ex vivo.The results show that the system has the potential for imaging and characterizing of EEC.

Correlation between Depth of Myometrial Invasion and Degree of Lymph Node Affection in Cases of Endometrial Cancer

Introduction: Endometrial cancer is the fourth most frequent cancer in females. Many factors can affect prognosis of this type of cancer, these mainly are the degree of myometrial invasion by the tumour, pelvic and paraaortic lymph node spread as well as the tumour histological type (endometrioid vs non-endometrioid type). transvaginal ultrasound (TVS) is a highly accurate and easy method for preoperative evaluation of myometrial invasion. Aim of the Work: The aim of this work is to assess if there is relation between the depth of myometrial invasion by the tumor and the rate of lymph node involvement in cases of endometrial cancer. Results: It was found that there was a significant relation between lymph node affection and the depth of myometrial invasion, all the positive lymph node affections cases had myomterial invasion > 50.0%. Conclusion: The incidence of pelvic lymph node affection is very high in cases where the myometrium is deeply infiltrated with the tumor. Assessment of myometrial invasion preoperatively by TVU and microscopically by pathological examination of the myometrium after hysterectomy provides an accurate estimation of the rate of pelvic lymph node affection and hence necessitates lymphadenectomy procedures in cases where myometrium is deeply infiltrated by the tumor and omitted in cases where it is tumor free.

Patterns of Recurrence in Low-Risk Endometrial Cancer

Objective: Endometrial cancer is the most common gynaecological cancer in high-income countries and has a good prognosis, particularly when diagnosed early. Early stage, low-grade endometrial cancer has a low risk of recurrence, and is detectable on routine follow up. This study aims to identify rates and patterns of recurrence in low-risk endometrial cancer patients and provide evidence for transitioning to community-based follow-up care. Methods: Retrospective study of patients with early-stage, low-grade endometrioid endometrial adenocarcinoma treated with surgery from January 1981 to December 2018. The rate and patterns of recurrence were identified and analysed. Results: Of 1215 eligible patients, 24 developed recurrent disease (1.98%). The majority of recurrences were pelvic (70%), and confined to the vaginal vault (41.7%). The median duration of follow up was 44.4 months, and time from primary surgery to diagnosis of recurrent disease was 30.5 months. No significant differences were found between the group of patients who recurred and the group of patients who did not. Twelve (50%) patients with recurrences were asymptomatic, but of these, 10 (83%) had obvious findings during routine surveillance physical examination. The remaining 12 patients (50%) presented with symptoms that prompted investigation that led to the recurrence diagnosis. 78% of recurrences were treated with combination therapy (surgical excision, chemotherapy, radiotherapy and hormonal). Ten patients (42%) had salvageable disease. For the non-salvageable cases, there was a mean of 2.1 years from recurrence diagnosis to death. Conclusions: The low recurrence rate of low-risk endometrial cancer following primary surgical management, and the feasibility of detection of recurrent disease, support transitioning surveillance to community-based settings.

Programmed cell death-1 inhibitor combination treatment for recurrent proficient mismatch repair/miscrosatellite-stable type endometrial cancer:A case report

BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies.However,clinical management of EC with checkpoint inhibitors requires improvement.Herein,we discuss a case of refractory proficient mismatch repair(pMMR)/miscrosatellitestable(MSS)EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies.CASE SUMMARY A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy.Four years later,she developed chest pain,and lung biopsy indicated thyroid transcription factor-1(-),Napsin A(-),estrogen receptor(+),progesterone receptor(+),anaplastic lymphoma kinase(D5F3)(-),and receptor tyrosine kinase(D4D6)(-)metastatic EC.Genetic testing results showed low tumor mutation burden,pMMR,PD ligand 1(-),MSS,and HLA-class 1 heterogeneous disease.The patient was started on toripalimab combined with nab-paclitaxel for seven cycles(every 3 wk),but this regimen was terminated because of an intolerable chemotherapy adverse event.The disease progressed in 2020,and the patient’s treatment was switched from nab-paclitaxel to anlotinib,while immunotherapy using toripalimab was continued.The patient achieved a major partial response with well-tolerated toxicities,and treatment is ongoing.CONCLUSION Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity.In this case,the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment.These results warrant further clinical exploration.