Fertility-sparing surgical interventions for low-risk, non-metastatic gestational trophoblastic neoplasia.

BACKGROUND: The primary treatment approach for addressing low-risk nonmetastatic gestational trophoblastic neoplasia (LR-NMGTN) in women desiring fertility preservation involves chemotherapy. An alternative option for treatment is fertility-sparing surgical interventions, either alone or in combination with adjuvant chemotherapy. The hypothesised advantages of choosing fertility-sparing surgery in cases of LR-NMGTN include potential avoidance of adverse effects associated with chemotherapy, potential reduction in the number of chemotherapy cycles required to achieve complete remission, and potential reduction in time to remission. OBJECTIVES: To measure the benefits and harms of fertility-sparing surgical interventions, with or without adjuvant chemotherapy, compared to primary chemotherapy alone, for the treatment of women with low-risk, non-metastatic gestational trophoblastic neoplasia (LR-NMGTN). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov and WHO ICTRP on 31 January 2024. We also searched abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing fertility-sparing surgical interventions, with or without subsequent adjuvant chemotherapy, versus primary chemotherapy as standard care for the treatment of women with LR-NMGTN. DATA COLLECTION AND ANALYSIS: We employed standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of evidence for each outcome, if available. We focused on the following outcomes: treatment success rate, relapse, disease-specific mortality, death due to treatment, pregnancy rate, quality of life, and any adverse events. MAIN RESULTS: We included two RCTs, with a total of 151 participants contributing data to our analyses. Both studies used uterine curettage as the fertility-sparing surgical intervention. Fertility-sparing surgical intervention without subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 62 participants with varying hCG (human chorionic gonadotrophin) levels evaluated this comparison. Most of our outcomes of interest were not measured in this study. The relative risk of experiencing any adverse event could not be estimated as chemotherapy adverse effects were not reported. The study reported that there were no surgical complications. Chemotherapy was administered to 50% of participants in the intervention group after curettage because their hCG levels increased. Fertility-sparing surgical intervention with subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 89 participants with hCG levels < 5000 IU/L evaluated this comparison. We judged the risk of bias in the study to be high. The evidence was very uncertain about the effect of uterine curettage with subsequent adjuvant chemotherapy on treatment success rate (RR 1.03, 95% CI 0.86 to1.23; 86 participants), relapse (RR 0.5, 95% CI 0.05 to 5.31; 86 participants), pregnancy rate (RR 0.86, 95% CI 0.31 to 2.34; 86 participants), and rate of adverse events (RR 1.15, 95% CI 0.63 to 2.13; 86 participants), all very low certainty evidence. The relative risks of disease-specific mortality and death due to treatment could not be estimated as there were no deaths in either group. There were no results for quality of life as this outcome was not reported. AUTHORS' CONCLUSIONS: Uterine curettage is the only fertility-sparing surgical intervention for LR-NMGTN that has been evaluated in a randomised controlled trial. The evidence is very uncertain about the benefits and harms of uterine curettage, with or without subsequent adjuvant chemotherapy, compared to primary chemotherapy alone. The two available studies are small with a high risk of bias, and future research may find substantially different results for all reported outcomes. Larger RCTs, with appropriate clinical outcome measures, would be required to determine the benefits or harms of fertility-sparing surgical interventions for this population.

Predicting Endometrial Hyperplasia and Endometrial Cancer on Recurrent Abnormal Uterine Bleeding.

OBJECTIVE: To develop predictive models for endometrial hyperplasia and endometrial cancer in patients with recurrent abnormal uterine bleeding (AUB). METHODS: This retrospective cohort study analyzed patients with recurrent AUB who had previous endometrial sampling that showed benign results between January 2013 and December 2021. A model was constructed from the significant factors associated with endometrial hyperplasia and endometrial cancer using multivariate logistic regression. Risk scores were calculated from the log odds of each significant predictive factor and were subsequently subcategorized into risk groups. The overall performance and internal validation of the model were assessed with the area under the receiver operating characteristic curve (AUC) and bootstrap methods. RESULTS: Of the total 456 patients with recurrent AUB, endometrial hyperplasia and endometrial cancer were detected in 8.3% and 2.2% of cases, respectively. The average interval between the first and second endometrial samplings was 25.1 months. Factors significantly associated with endometrial hyperplasia and endometrial cancer included age older than 45 years (odds ratio [OR] 2.86, 95% CI, 1.31-7.03), nulliparity (OR 3.50, 95% CI, 1.76-6.85), a history of endometrial polyp (OR 3.69, 95% CI, 1.93-7.05), and an interval of less than 12 months between sampling (OR 2.36, 95% CI, 1.25-4.42). Predictive factors were scored and categorized into three groups: 0-3, 5-8, and 9-11 points. The corresponding risks for endometrial hyperplasia and endometrial cancer in these groups were 4.7%, 15.5%, and 57.1%, respectively. The AUC was 73.1%, with a mean absolute error of 0.01. CONCLUSION: Endometrial hyperplasia and endometrial cancer occur at low incidence among one-fifth of patients with AUB who experience recurrent bleeding. Older age, nulliparity, a history of endometrial polyps, and an interval of less than 12 months between samplings are predictive factors for endometrial hyperplasia and endometrial cancer in this cohort.

Significance of Pretreatment Hemoglobin-Albumin-Lymphocyte-Platelet Index for the Prediction of Suboptimal Surgery in Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancer (EOC) is the leading cause of death in gynecological cancers in developed countries. In recent years, there has been a growing need for economical and accurate pretreatment laboratory investigations to assess the prognosis of patients with advanced EOC (AEOC). We aimed to investigate the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) index in suboptimal cytoreduction and oncological outcomes. Methods: A prognostic prediction model for diagnosing suboptimal cytoreduction for patients with AEOC receiving neoadjuvant chemotherapy (NACT) was developed. Multivariate logistic regression analysis was performed to identify the independent predictors of suboptimal cytoreduction, with a P-value < 0.05, and then transformed into risk-scoring systems. Internal validation was performed using the bootstrapping procedure, and predictive cytoreduction (PSC) scores were compared using non-parametric receiver operating characteristic (ROC) regression. Survival analysis was performed using Kaplan-Meier estimation and Cox proportional regression. Results: In total, 473 patients were analyzed, and the rate of suboptimal surgery was 43%. A scoring system in predicting suboptimal cytoreduction included age, cancer antigen (CA)-125 level before surgery, performance status, cycles of chemotherapy, peritoneal cancer index, and HALP index ≤ 22.6. The model had good discriminative ability (area under the ROC (AUROC), 0.80; 95% confidence interval (CI), 0.76 - 0.84), outperforming the PSC score (AUROC, 0.75; 95% CI, 0.71 - 0.80). The score was divided into the low-risk (positive predictive value (PPV), 22.4; 95% CI, 17.8 - 27.7), moderate-risk (PPV, 65.9; 95% CI, 56.9 - 74.0), and high-risk (PPV, 90.6; 95% CI, 79.3 - 96.9) groups. The HALP index score of ≤ 22.6 was independently associated with progression-free survival (hazard ratio (HR), 2.92; 95% CI, 1.58 - 5.40) and overall survival (HR, 2.66; 95% CI, 1.57 - 4.49). Conclusion: The HALP index is a newly predicted factor for suboptimal cytoreduction and oncological outcomes in patients with AEOC after NACT.

Effect of time interval between surgery and the initiation of adjuvant therapy on the oncologic outcomes of early-stage endometrial cancer.

OBJECTIVE: To identify the impact of time interval between surgery and initial adjuvant radiotherapy on oncologic outcomes in early-stage endometrial cancer. METHODS: This retrospective cohort study included patients with stage I/II endometrial cancer who underwent surgical staging and adjuvant therapy at Songklanagarind Hospital from January 1, 2007, to December 31, 2017. Patients were categorized into two groups: TI <6 weeks and TI ≥6 weeks. The effects of TI and clinicopathological factors on recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox proportional-hazards regression. RESULTS: In total, 177 patients were enrolled, with 52% receiving adjuvant radiotherapy at <6 weeks (overall median TI 5.7 weeks). The recurrence and death rates were 13% and 10.2%, respectively. The median follow-up time was 46.6 months. The overall 3-year RFS and OS rates were 88.2% and 85.2%, respectively. The TI significantly affected the 3-year RFS (94.4% vs 81.2%; P = 0.008) and 3-year OS (95.5% vs 83.2%; P = 0.012) in patients with TI <6 and ≥6 weeks, respectively. In multivariate analysis, the depth of myometrial invasion (MI), presence of lymphovascular space invasion, and TI were independent prognostic factors for both RFS and OS. Delaying the TI (≥6 weeks) was significantly associated with a worse RFS (hazard ratio [HR] 3.70; 95% confidence interval [CI]: 1.34-10.22; P = 0.012) and an inferior OS (HR 3.80; 95% CI: 1.23-11.69; P = 0.02). CONCLUSION: A delay in the TI between surgery and the initiation of adjuvant radiotherapy of ≥6 weeks negatively affected the oncologic outcomes in early-stage endometrial cancer.

Hormone replacement therapy after surgery for epithelial ovarian cancer.

BACKGROUND: Women who have undergone surgical treatment for epithelial ovarian cancer (EOC) may develop menopausal symptoms due to immediate loss of ovarian function following surgery and chemotherapy. Women may experience vasomotor symptoms, sleep disturbance, difficulty concentrating, sexual dysfunction, vaginal symptoms and accelerated osteoporosis. Although hormone replacement therapy (HRT) is the most effective treatment to relieve these symptoms, its safety has been questioned for women with EOC. OBJECTIVES: To assess the safety and efficacy of HRT for menopausal symptoms in women surgically treated for EOC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 6), MEDLINE via Ovid (1946 to 12 June 2019) and Embase via Ovid (1980 to 2019, week 23). We also handsearched conference reports and trial registries. There was no language restriction. SELECTION CRITERIA: We included randomized controlled trials (RCTs) with participants of any age and menopausal status who had undergone surgery for EOC and, after diagnosis and treatment, used any regimen and duration of HRT compared with placebo or no hormone therapy. We also included trials comparing different regimens or duration of administration of HRT. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies that met the inclusion criteria. They used Covidence to extract study characteristics, outcome data and to assess methodological quality of the included studies. MAIN RESULTS: Our search strategy identified 2617 titles, of which 2614 titles were excluded. Three studies, involving 350 women, met our inclusion criteria. Two of the studies included pre and postmenopausal women, and the third only included premenopausal women. The overall age range of those women included in the studies was 20 to 89.6 years old, with a median follow-up ranging from 31.4 months to 19.1 years. The geographical distribution of participants included Europe, South Africa and China. All stages and histological subtypes were included in two of the studies, but stage IV disease had been excluded in the third. The three included studies used a variety of HRT regimens (conjugated oestrogen with or without medroxyprogesterone and with or without nylestriol) and HRT administrations (oral, patch and implant), In all studies, the comparisons were made versus women who had not received HRT. The studies were at low or unclear risk of selection and reporting bias, and at high risk of performance, detection and attrition bias. The certainty of the evidence was low for overall survival and progression-free survival, and very low for quality-of-life assessment, incidence of breast cancer, transient ischaemic attack (TIA), cerebrovascular accident (CVA) and myocardial infarction (MI). Meta-analysis of these studies showed that HRT may improve overall survival (hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.54 to 0.93; 350 participants, 3 studies; low-certainty evidence). Quality-of-life assessment by use of the EORTC-C30 questionnaire was performed only in one study. We are uncertain whether HRT improves or reduces quality of life as the certainty of the evidence was assessed as very low (mean difference (MD) 13.67 points higher, 95% CI 9.26 higher to 18.08 higher; 1 study; 75 participants; very low-certainty evidence). Likewise, HRT may make little or no difference to progression-free survival (HR 0.76, 95% CI 0.57 to 1.01; 275 participants, 2 studies; low-certainty evidence). We are uncertain whether HRT improves or reduces the incidence of breast cancer (risk ratio (RR) 2.00, 95% CI 0.19 to 21.59; 225 participants, 2 studies; very low-certainty evidence); TIA (RR 5.00, 95% CI 0.24 to 102.42; 150 participants, 1 study; very low-certainty evidence); CVA (RR 0.67, 95% CI 0.11 to 3.88; 150 participants, 1 study; very low-certainty evidence); and MI (RR 0.20, 95% CI 0.01 to 4.10; 150 participants, 1 study; very low-certainty evidence). The incidence of gallstones was not reported in the included studies. AUTHORS' CONCLUSIONS: Hormone replacement therapy may slightly improve overall survival in women who have undergone surgical treatment for EOC, but the certainty of the evidence is low. HRT may make little or no difference to quality of life, incidence of breast cancer, TIA, CVA and MI as the certainty of the evidence has been assessed as very low. There may be little or no effect of HRT use on progression-free survival. The evidence in this review is limited by imprecision and incompleteness of reported relevant outcomes and therefore the results should be interpreted with caution. Future well-designed RCTs are required as this is an important area to women experiencing menopausal symptoms following surgical treatment for ovarian cancer, especially as doctors are often reluctant to prescribe HRT in this scenario. The evidence in this review is too limited to support or refute that HRT is very harmful in this population.

Trends in incidence of uterine cancer in Songkhla, Southern Thailand.

OBJECTIVE: To define the present incidence of uterine cancer and the trends of incidence in the future. Additional, subgroup analysis in religion and socio-demographic factors will be analyzed. METHODS: The data of uterine cancer from The Songkhla Cancer Registry between; 1989 and 2016, was extracted. The population denominators of Songkhla Province were referred from the information of the population censuses surveyed by the National Statistical Office. The incidence was estimate by; the age specific rate, and analyzed in trend incidence using Jointpoint and Age-period-cohort; APC regression models and trend projection in 2017-2030 using by Jointpoint, the NordPred and APC model. The comparison of incidence according to habitat and religion were unpaired t-test. RESULTS: The incidence of uterine cancer in Songkhla Province increased from 1.5, to 5.3 per 100,000 women-years in 2016, and 8 per 100,000 women-years in 2030. The incidence was more in urban areas and in Buddhists. CONCLUSION: The incidence of uterine cancer is increasing. The policy, which promotes protective factors and control risk factors, would decrease incidence of endometrial cancer, and other estrogen dependent cancers additional to chronic diseases from the cardiovascular system.

Diagnostic Performance and Agreement of Preoperative, Intraoperative Evaluations, and Final Pathology for Lymphadenectomy and Lymph Node Involvement in Endometrial Cancer

Objective: To determine the accuracy of clinical parameters examined by preoperative and intraoperative evaluations compared with final histological results in patients with endometrial cancer, and to evaluate the application of preoperative investigations, intraoperative evaluations, and final histological results in predicting lymph node involvement Material and Method: The medical records of the patients diagnosed with endometrial cancer who had surgical staging between January 1, 2006 and December 31, 2012 at Songklanagarind Hospital were retrospectively reviewed. The agreement of clinical parameters identified through preoperative investigations and intraoperative evaluations with the final histology findings were calculated using kappa statistics. The diagnostic performance of preoperative investigations, intraoperative evaluations, and final histological results to predict lymph node involvement were calculated in terms of sensitivity, specificity, positive predictive value, and negative predictive value. Results: Preoperative investigations showed a slight to fair agreement whereas intraoperative evaluations had a fair to moderate agreement in detecting clinical parameters compared with the final histological results. Endocervical curettage and endometrial biopsy exhibited the highest sensitivity, pelvic ultrasonography the highest specificity, and intraoperative evaluations had a high-level sensitivity and specificity Conclusion: Preoperative investigations have role as an adjunctive evaluation, whereas intraoperative gross assessment remains the most accurate and useful method of detecting patients for lymphadenectomy.

Comparison of Clinical Manifestations and Survival Outcomes between Neuroendocrine Tumor and Squamous Cell Carcinoma of the Uterine Cervix: Results from a Tertiary Center in Southern Thailand.

OBJECTIVE: To study the clinical manifestations and survival outcomes of neuroendocrine tumor of the uterine cervix (NTUC) and compare them with those of squamous cell carcinoma (SCCA) MATERIAL AND METHOD: A case-control study was conducted. In the study group, we included patients whose tumors were described in the original pathology reports as NTUC. For the control group, we calculated the sample size based on a formula according to survival rate. The ratio of cases to controls was 1:4. Patients with a diagnosis of SCCA of the uterine cervix and treated between January 2003 and December 2011 in Son gklanagarind Hospital were included in the control group according to stage and year of NT UC diagnos is. The patients 'characteristics, method of treatment, treatment outcomes, and survival of the two groups were compared. The prognostic factors among patients with NTUC were analyzed using the Cox regression. RESULTS: Of the 2,835 cervical carcinoma cases studied, 44 (1.6%) were NTUC. NTUC patients had a lower mean age at diagnosis, received more multimodality treatments, had a lower complete response rate, a higher recurrence rate, and more distant metastasis than their SCCA counterparts. A significantly lower 2-year and 5-year survival was detected in NTUC compared with SCCA (62% and 52% vs. 97% and 85%, respectively, p < 0.01). In the univariate analysis, the number of sexual partners, stage of disease, surgery treatment, status of response, and site of recurrence predicted a poorer overall survival in NTUC. However, these factors were not found to be statistically significant prognostic factors on multivariate analysis. CONCLUSION: A poorer treatment outcome and prognosis were found in NTUC compared with SCCA. Moreover a poorer prognosis was observed in NTUC patients with an advanced-stage disease, non-surgery treatment, progressive disease, and distant metastasis recurrence than in those with SCCA patients. Multimodality treatments should be considered in NTUC to improve survival. Additionally close monitoring may be necessary in this group of patients.

Predictors of the residual disease of high-grade lesions and microinvasive squamous cell carcinoma of the cervix following conization.

OBJECTIVE: To determine the predictors of residual disease of high-grade lesion (HGL) and microinvasive squamous cell carcinoma of the cervix (MICA) in subsequent hysterectomy following conization. MATERIAL AND METHOD: The medical records of women who underwent any conizations diagnosed of HGL and MICA and followed by subsequent hysterectomy within 6 months were retrospectively reviewed. A case and control was defined as whether or not a residual disease of HGL or more was detected in cervical tissue from hysterectomy after conization. Demographic characteristics and pathological features of cases and controls were recorded independently and blindly. Univariate and multivariate analysis were used. The Receiver Operating Characteristics curve of predictors was created using the fitting value obtained from a logistic regression model. RESULTS: A total of 185 women were diagnosed during January 1, 1997 and July 31, 2008 including 102 women without a residual disease and 83 with residual disease at cervical tissue from hysterectomy. The multivariate analysis showed that postmenopausal status (OR = 3.5, 95% CI = 1.8-6.7), number of quadrant involvement (OR = 3.8, 95% CI = 1.8-8.3), internal margin involvement (OR = 3.8, 95% CI = 1.7-8.2), severe nuclear atypia (OR = 2.0, 95% CI = 1.1-3.8) and high mitotic activity (OR = 2.1, 95% CI = 1.1-3.7) were the predictors of residual disease in hysterectomy specimens after conization. Three or more predictors involved predicted the detection of residual disease. CONCLUSION: The presence of postmenopause, three or four quadrants involved, positive internal margin, severe nuclear atypia and high mitotic activity could be used to predict residual lesions after conization.