Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer.

BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. MATERIALS AND METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low. CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.

Simple hysterectomy versus radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: This systematic review (SR) and meta-analysis aims to compare the surgery-related results and oncological outcomes between SH and RH in patients with early-stage cervical cancer. METHOD: We systematically searched databases including PubMed, Embase and Cochrane to collect studies that compared oncological and surgery-related outcomes between SH and RH groups in patients with stage IA2 and IB1 cervical cancer. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Seven studies comprising 6977 patients were included into our study. For oncological outcomes, we found no statistical difference in recurrence rate [OR = 0.88; 95% CI (0.50, 1.57); P = 0.68] and Overall Survival (OS) [OR = 1.23; 95% CI (0.69, 2.19), P = 0.48]. No difference was detected in the prevalence of positive LVSI and lymph nodes metastasis between the two groups. Concerning surgery-related outcomes, the comprehensive effects revealed that the bladder injury [OR = 0.28; 95% CI (0.08, 0.94), P = 0.04] and bladder disfunction [OR = 0.10; 95% CI (0.02, 0.53), P = 0.007] of the RH group were higher compared to the SH group. CONCLUSION: This meta-analysis suggested there are no significant differences in terms of both recurrence rate and overall survival among patients with stage IA2-IB1 cervical cancer undergoing SH or RH, while the SH group has better surgery-related outcomes. These data confirm the need to narrow the indication for RH in early-stage cervical cancer.

Response to treatment and prognostic significance of supradiaphragmatic disease in patients with high-grade serous ovarian cancer.

OBJECTIVES: This study was designed to investigate the response to chemotherapy of supradiaphragmatic disease diagnosed by preoperative imaging. As secondary objectives, oncologic outcomes of patients affected by supradiaphragmatic disease and their pattern of recurrence were also evaluated. METHODS: Data of consecutive patients with newly diagnosed FIGO stage IV (for supradiaphragmatic disease) epithelial ovarian cancer undergoing either primary debulking surgery or neoadjuvant chemotherapy plus interval debulking surgery between 2004 and 2021, were retrospectively collected. All patients were preoperatively evaluated by chest/abdominal CT scan or 18F-FDG PET/CT preoperatively and at follow-up to evaluate response to chemotherapy. At follow-up visits, site of recurrence diagnosed by imaging techniques was systematically recorded as it occurred. Progression-free and overall survival were measured by using Kaplan-Meier and Cox models. RESULTS: A total of 130 patients was included in this study with a median (range) follow-up of 32.9 (12.8-176.7) months. Complete or partial response was achieved in most of the patients after 3 cycles (77.7%) and 6 cycles (85.4%) of chemotherapy. At follow-up, recurrence occurred in 96 (73.8%) patients and the main site of recurrence was abdomen only in 64 (66.7%) patients. At multivariate analysis, residual disease after surgery was the only variable influencing survival outcomes. CONCLUSIONS: Supradiaphragmatic disease respond to chemotherapy in most patients affected by advanced EOC and recurrence mainly occurs in the abdomen. Results from this study confirms that abdominal optimal cytoreduction is the main surgical goal in the treatment of women affected by FIGO stage IV EOC.

Surgical morbidity of total laparoscopic hysterectomy for benign disease: Predictors of major postoperative complications.

OBJECTIVE: To estimate rate of perioperative complications and to define risk factors of 30-day major (Clavien-Dindo ≥ 2) postoperative complications of total laparoscopic hysterectomy (TLH) for benign disease. STUDY DESIGN: An uncontrolled single-center single-arm retrospective study. Data of consecutive patients who have undergone TLH for pathologically confirmed benign disease between January 2000 and December 2019 have been analyzed. Perioperative surgical outcomes, occurrence of postoperative complications, readmissions, and reoperations within 30 days from surgery were registered. Univariate and multivariable analyses were performed to determine the factors associated with major (Clavien-Dindo ≥ 2) postoperative complications. RESULTS: Over the study period 3090 patients were included in the study. Conversion to open surgery occurred in 54 (1.7%) cases. Mean operative time for TLH was 87.7 (±1.7) minutes while mean estimated blood loss was 119.5 (+7.4) mL. Overall, postoperative complications were registered in 430 (13.9%) patients, and major events were observed in 208 (6.7%) of the cases. Same-hospital readmissions and reoperations within 30-day from surgery occurred in 78 (2.5%) and 28 (0.9%) patients, respectively. At multivariable analysis, endometriosis (odds ratio: 3.51, 95%CI:1.54-8.30, p = 0.02), the need for conversion to open surgery (odds ratio: 1.26, 98%CI:1.03-12.64, p < 0.001), and the occurrence of any intraoperative complication (odds ratio: 3.10, 95%CI: 1.45-21.61, p < 0.001) were found as independent risk factors for major postoperative complications. CONCLUSIONS: Total hysterectomy performed via laparoscopy is associated with acceptable major postoperative complications rate. A huge effort should be made to minimize the occurrence of intraoperative complications and the need for conversion to open surgery. Patients undergoing TLH for endometriosis should be counselled about the increased risk of major postoperative events.

Using rADioMIcs and machine learning with ultrasonography for the differential diagnosis of myometRiAL tumors (the ADMIRAL pilot study). Radiomics and differential diagnosis of myometrial tumors.

OBJECTIVE: To develop and evaluate the performance of a radiomics and machine learning model applied to ultrasound (US) images in predicting the risk of malignancy of a uterine mesenchymal lesion. METHODS: Single-center retrospective evaluation of consecutive patients who underwent surgery for a malignant uterine mesenchymal lesion (sarcoma) and a control group of patients operated on for a benign uterine mesenchymal lesion (myoma). Radiomics was applied to US preoperative images according to the International Biomarker Standardization Initiative guidelines to create, validate and test a classification model for the differential diagnosis of myometrial tumors. The TRACE4 radiomic platform was used thus obtaining a full-automatic radiomic workflow. Definitive histology was considered as gold standard. Accuracy, sensitivity, specificity, AUC and standard deviation of the created classification model were defined. RESULTS: A total of 70 women with uterine mesenchymal lesions were recruited (20 with histological diagnosis of sarcoma and 50 myomas). Three hundred and nineteen radiomics IBSI-compliant features were extracted and 308 radiomics features were found stable. Different machine learning classifiers were created and the best classification system showed Accuracy 0.85 ± 0.01, Sensitivity 0.80 ± 0.01, Specificity 0.87 ± 0.01, AUC 0.86 ± 0.03. CONCLUSIONS: Radiomics applied to US images shows a great potential in differential diagnosis of mesenchymal tumors, thus representing an interesting decision support tool for the gynecologist oncologist in an area often characterized by uncertainty.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

OBJECTIVES: The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. METHODS: Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. RESULTS: Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. CONCLUSIONS: Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted.

Management of endometrial cancer: issues and controversies.

Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE: Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS: Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS: PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS: Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Interobserver reliability to interpret intrapartum electronic fetal heart rate monitoring: Does a standardized algorithm improve agreement among clinicians?

Our aim was to investigate the accuracy in predicting intrapartum fetal acidaemia and the interobserver reproducibility of a mathematical algorithm for the interpretation of electronic fetal heart rate (FHR) monitoring throughout labour. Eight physicians (blinded to the clinical outcomes of the deliveries) evaluated four randomly selected intrapartum FHR tracings by common visual interpretation, trying to predict umbilical artery base excess at birth. They subsequently were asked to re-evaluate the tracings using a mathematical algorithm for FHR tracing interpretation. Common visual interpretation allowed a correct estimation of the umbilical artery base excess in 34.4% of cases, with a poor interobserver reproducibility (Kappa correlation coefficient = 0.24). After implementation of the algorithm, the proportion of correct estimates significantly increased to 90.6% (p < 0.001), with excellent inter-clinician agreement (κ: 0.85). To conclude, incorporation of a standardised algorithm reduces the interobserver variability and allows a better estimation of fetal acidaemia at birth.

Prediction of fetal base excess values at birth using an algorithm to interpret fetal heart rate tracings: a retrospective validation.

OBJECTIVE: To evaluate whether a standardised algorithm to interpret fetal heart rate (FHR) tracings during the entire length of labour can predict umbilical artery base excess at birth, and to investigate its inter- and intra-observer reproducibility. DESIGN: Retrospective study. SETTING: Obstetrics and gynaecology department at a tertiary referral centre in a university hospital. POPULATION: Group 1: 152 consecutive, generally low-risk, labouring women. Group 2: mixed group of 30 women who delivered a fetus with pH < 7.00 and 30 women who delivered a fetus with pH ≥ 7.00. METHODS: Intrapartum FHR tracings were retrospectively and blindly evaluated by two independent assessors using an algorithm proposed by Ross and Gala to predict fetal base excess at birth. MAIN OUTCOME MEASURES: The accuracy in predicting the base excess values of newborns was expressed as the proportion of FHR tracings in which the operator was able to correctly calculate the actual base excess at birth (approximation of ± 2 mmol/l). Inter- and intra-observer reproducibility were estimated using the Pearson correlation coefficient. RESULTS: In the group of 152 low-risk labouring women, the two assessors correctly predicted the umbilical artery base excess in 73.1 and 76.3% of cases, respectively. Inter-observer (Pearson correlation coefficient = 0.75) and intra-observer (Pearson correlation coefficient = 0.80 and 0.82 for the first and second assessor, respectively) reproducibility was very good. In the 30 fetuses that were acidemic, the first and second observers correctly predicted base excess values in 23 (76.7%) and 21 (70%) cases, respectively (inter-observer reproducibility, Pearson correlation coefficient = 0.72). CONCLUSIONS: The algorithm proposed by Ross and Gala may be a valuable tool to estimate changes in umbilical base excess during active labour, with a high inter- and intra-observer reproducibility.