Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer.

OBJECTIVE: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer. METHODS: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically. Prespecified PRO analyses focused on disease-related abdominal pain and bloating symptoms (European Organisation for Research and Treatment of Cancer QLQ-OV28), functioning, and health-related quality of life (HRQoL) (QLQ-C30). RESULTS: After 38 months' median follow-up, the OS hazard ratio in the PD-L1-positive population was 0.83 (95% CI, 0.66-1.06; p = 0.13); median OS was not estimable with atezolizumab versus 49.2 months with placebo. The hazard ratio for OS in the ITT population was 0.92 (95% CI, 0.78-1.09; median 50.5 versus 46.6 months, respectively). At week 9, similar proportions of patients in both arms of the neoadjuvant cohort showed ≥10-point improvement from baseline in abdominal pain and bloating, functioning, and HRQoL. In the primary surgery cohort, similar proportions of patients in each arm had improved, stable, or worsened physical and role function and HRQoL from baseline over time. Neither cohort showed differences between arms in treatment-related symptoms or overall side-effect bother. CONCLUSIONS: Incorporation of atezolizumab into standard therapy for newly diagnosed ovarian cancer does not significantly improve efficacy or impose additional treatment burden for patients. CLINICALTRIALS: gov registration: NCT03038100.

The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study.

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

STRN-ALK rearranged malignant peritoneal mesothelioma-Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma.

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial.

PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates. RESULTS: Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors. CONCLUSIONS: Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors. See related commentary by Al-Rawi et al., p. 1645.

IVF characteristics and the molecular luteal features of random start IVF cycles are not different from conventional cycles in cancer patients.

STUDY QUESTION: Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional cycles in cancer patients? SUMMARY ANSWER: No; controlled ovarian stimulation cycles randomly started at late follicular phase (LFP) and luteal phase (LP) are totally comparable to those conventional IVF cycles started at early follicular phase (EFP) in terms of the expression of the enzymes involved in cholesterol utilization and steroid hormone biosynthesis pathways, gonadotropin receptor expression and, estradiol (E2) and progesterone (P4) production in addition to the similarities in ovarian response to gonadotropin stimulation, oocyte yield, fertilization rate and embryo development competency in cancer patients. WHAT IS KNOWN ALREADY: Random start ovarian stimulation protocols are commonly employed for oocyte and embryo freezing for fertility preservation in cancer patients with time constraints who do not have sufficient time to undergo ovarian stimulation initiated conventionally at EFP of the next cycle. No data is available regarding the molecular steroidogenic features of these cycles analyzed together with the clinical IVF characteristics in cancer patients. We aimed to address this question in this study to help understand how similar the random start cycles are to the conventional start ones. STUDY DESIGN, SIZE, DURATION: A clinical translational research study conducted in 62 cancer patients undergoing IVF for fertility preservation between the years 2017 and 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty-two patients who were diagnosed with different types of cancer and underwent ovarian stimulation for oocyte (n = 41) and embryo (n = 21) cryopreservation using GnRH antagonist protocol and human menopausal gonadotropins before receiving cancer treatment/surgery were enrolled in the study. For patients with breast cancer and endometrial cancer the aromatase inhibitor letrozole was used with gonadotropin stimulation. Ovarian stimulation was initiated conventionally at EFP in 22 patients and served as control while it was started at LFP in 20, and mid-LP in the other 20 patients. The luteinized granulosa cells (GCs) were recovered from follicular aspirates during oocyte retrieval procedure and used for the experiments separately for each individual patient. The expression of the enzymes involved in sex steroid biosynthesis (StAR, 3ß-HSD, Aromatase) and cholesterol synthesis (3-hydroxy 3-methylglutaryl Co-A reductase (HMG-Co-A reductase)), utilization (hormone sensitive lipase (HSL)), and storage (Acetyl-Coenzyme A acetyltransferase 1 (ACAT-1)), and gonadotropin receptor expression status were analyzed using immunoblotting and RT-PCR methods. Laser confocal immunofluorescence imaging was applied to analyze and compare the expression patterns of the steroidogenic enzymes and their relation with mitochondria. In vitro E2 and P4 production by the cells were compared among the groups. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline demographic and IVF characteristics of the patients undergoing the conventional start and random start IVF cycles were similar. Duration of gonadotropin stimulation was significantly longer in LFP and LP start cycles in comparison to the conventional ones. Ovarian response to gonadotropin stimulation, mature and total oocyte yield, fertilization and Day 5 blastulation rates of the embryos were comparable between the conventional versus random start cycles. When the luteal GCs of these random start cycles were analyzed we could not find any gross differences between these cycles in terms of the viability index and gross light microscopic morphologic features. More detailed analysis of the molecular luteal characteristics of the cells using RT-PCR, immunoblotting methods revealed that the expression profiles of the gonadotropin receptors, and the enzymes involved in sex steroid biosynthesis and cholesterol synthesis/utilization, and the steroidogenic activity of the luteal GCs of the random start cycles are almost identical to those of the conventional start cycles. Confocal image analysis demonstrated similar patterns in the signal expression profiles of the steroidogenic enzymes and their co-localization within mitochondria. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Caution should be exercised when interpreting our data and counseling cancer patients seeking fertility preservation because it is still unclear if previous exposure to cancer drugs, different ovarian pathologies or infertility etiologies, previous ovarian surgery and/or any other underlying diseases that are concomitantly present with cancer may cause a difference between conventional and random start stimulation protocols in terms of IVF parameters, luteal function and reproductive outcome. Relatively low number of patients in each stimulation protocol and pooling of luteal GCs for each patient rather than individual analysis of each follicle and oocyte are additional limitations of our study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide reassurance that random start protocol offers cancer patients an equally good prospect of fertility preservation as conventional IVF. STUDY FUNDING/COMPETING INTEREST(S): Funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Hyperthermic intraperitoneal chemotherapy in the treatment of recurrent ovarian cancer: When, and for whom?

OBJECTIVE: The aim of this study is to evaluate the progression-free survival (PFS) of recurrent ovarian cancer (ROC) patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). MATERIALS AND METHODS: ROC patients who underwent cytoreductive surgery plus HIPEC between 2015 and 2021 were retrospectively evaluated. Patients' demographic information and clinicopathological characteristics including cancer type, histology, platinum status, presence of ascites, type of surgery, complications, chemotherapy history, and disease progression were documented. PFS was calculated using the Kaplan-Meier method. RESULTS: A total of 104 patients with ROC were included. The median age was 57 years and the median follow-up time was 15 months (range: 5-69 months). In Cox regression multivariate analyses, platinum resistance (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.91-5.76, p = 0.00), more than one relapse prior HIPEC (HR: 2.81, 95% CI: 1.65-4.87, p = 0.024), and presence of ascites (HR: 1.88, 95% CI: 1.08-3.26, p = 0.00) were found to be negative prognostic factors for PFS. In subgroup analyses of patients with the first recurrence, the median PFS was 21 months for platinum-sensitive patients and 6 months for platinum-resistant patients (p = 0.032). CONCLUSION: HIPEC at the time of first platinum-sensitive relapse may lead to favorable PFS in the treatment ROC. However, HIPEC as salvage treatment even with R0 cytoreductive surgery does not seem effective.

Perspectives of Gynecologic Oncologists on Minimally Invasive Surgery During COVID-19 Pandemic: A Turkish Society of Minimally Invasive Gynecologic Oncology (MIJOD) Survey.

BACKGROUND: To evaluate gynecologic oncologists' trends and attitudes towards the use of Minimally invasive surgery (MIS) in active period of the COVID-19 pandemic in Turkey. METHODS: Online national survey sent to members of Turkish Endoscopy Platform consisting of six sections and 45 questions between the dates 1-15 June 2020 in Turkey to explore their surgical practice during the pandemic in three hospital types: Education and research hospital/university hospital, state hospital and private Hospital. Participants were gynecologic oncologists who are members of Turkish Endoscopy Platform. RESULTS: Fifty-eight percent of participants canceled all operations except for cancer surgeries and emergent operations. About a quarter of participants (28%) continued to operate laparoscopically and/or robotically. For the evaluation of the suspected adnexial mass (SAM) 64% used laparotomy and only 13 % operated by laparoscopy (L/S). For the management of low-risk early-stage endometrial cancer only fifth of the participants preferred to perform L/S. For endometrial cancer with high-intermediate risk factors more than half of participants preferred complete staging with laparotomy. For advanced stage ovarian cancer, one-fifth of the participants preferred to perform an explorative laparotomy, whilst 15 % preferred diagnostic laparoscopy to triage the patients for either NACT or cytoreductive surgery. On the contrary 41 % of participants chose to have cytology by paracentesis for neo-adjuvant chemotherapy (NACT). Gynecologic oncologists with >10 years L/S experience used MIS more for SAM. Furthermore, experienced surgeons used L/S more for endometrial cancer patients. In busy COVID hospitals, more participants preferred laparotomy over L/S. CONCLUSION: Use of MIS decreased during the pandemic in Turkey. More experienced surgeons continued to perform MIS. Surgical treatment was the preferred approach for SAM, early-stage endometrial cancer.  However, NACT was more popular compared to radical surgery.

Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006).

INTRODUCTION: This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. METHODS: Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. RESULTS: Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. CONCLUSION: SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Mini-plus percutaneous setting in total laparoscopic hysterectomy.

INTRODUCTION: We aimed to analyze the preliminary experience of a mini-plus percutaneous instrument (MpPc) setting in total laparoscopic hysterectomy (TLH). MATERIAL AND METHODS: Forty-three women who underwent a mini-plus percutaneous total laparoscopic hysterectomy at a tertiary-care university-based teaching hospital and academic affiliated private hospital between May 2017 and 2018 were included. MpPc-TLH was performed through one optical trans-umbilical 5-mm trocar, one 5-mm ancillary port on the right side, either one 2.4-mm percutaneous endoscopic instrument or 3-mm mini-laparoscopic port on the right upper quadrant and if required one 3-mm ancillary port on the left lower quadrant. RESULTS: A total of 43 patients were included, with a median age of 48 years (range, 38-71 years). Indication for surgery included uterine myomas (n = 20), benign adnexal mass (n = 7), endometrial intraepithelial neoplasia (n = 6), endometrial cancer (n = 5), adenomyosis with abnormal bleeding (n = 3), and high-grade cervical dysplasia (n = 2). The median operating time was 100 min (range, 60-180 min), and the median estimated blood loss was 30 ml (range, 20-60ml). The median postoperative abdominal pain Visual Analog Scale score was 3 (range, 0-6). CONCLUSIONS: The preliminary data suggest that MpPc approach is a feasible and safe surgical modality for total laparoscopic hysterectomy.

The safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era: a multicentre, retrospective, case-control study.

Our goal was to address the safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era. The databases of seven gynaecologic cancer centres were searched in order to identify all consecutive gynaecologic cancer patients undergoing major surgery between March 11, 2020 and May 15, 2020 for this retrospective, case-control study. The case group consisted of patients with histopathologically confirmed gynaecologic cancers, and each case was matched with two counterparts who had undergone primary surgery before the COVID-19 pandemic. The case and the control groups were compared in terms of length of hospital stay, admission to the intensive care unit (ICU), intraoperative and postoperative complications.During the study period, 154 women with gynaecologic cancer undergoing major surgery were identified. Although the case group had more co-morbidities compared to the control group (103/154 vs. 178/308, respectively; p = .04), the median length of hospital stays, the rate of ICU admission, intraoperative complication rates and postoperative complication rates were similar in the two groups. Gynaecologic cancer surgery may be performed safely in the COVID-19 era with similar rates of ICU admission, intraoperative and postoperative complications compared to the patients operated before the COVID-19 pandemic.IMPACT STATEMENTWhat is already known on this subject? Many societies have announced their guidelines about the surgical management of gynaecologic cancer patients during the COVID-19 pandemic. However, most of them are not evidence-based and mostly on expert opinions.What do the results of this study add? The main findings of this retrospective, case-control study indicate that the short-term (30 day) outcomes of gynaecologic cancer patients undergoing major surgery in the COVID-19 era are similar to those who had been operated before the COVID-19 pandemic. The length of hospital stays, the rates of admission to the ICU, intraoperative and postoperative complications were comparable between women undergoing major gynaecologic cancer surgery in the COVID-19 era and the women who had been operated before the pandemic.What are the implications of these findings for clinical practice and/or further research? We can suggest that definitive surgery may be performed for gynaecologic cancer patients in the COVID-19 era if the resources permit and appropriate precautions such as social distancing, isolation and the use of personal protective equipment are taken.

Complications of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: An evaluation of 100 cases.

OBJECTIVE: To evaluate the perioperative outcomes and complications of patients with peritoneal carcinomatosis who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This retrospective study included 100 patients operated on between 2016 and 2020. Patients' characteristics, including age, comorbidities, chemotherapy history, treatment failures, cancer type, histology, platinum sensitivity, and perioperative complications, were documented. Perioperative complications were classified according to the Clavien-Dindo classification. RESULTS: Median age was 58 years and median follow-up time was 16 months. Eighty-six (86%) patients had ovarian cancer; 11 (11%) experienced grade III-IV complications, and the only relevant factor was the presence of multiple metastasis (P = 0.031). Seven patients (7%) had surgical-site infection; in multivariant analyses, only ostomy formation was found as an independent risk factor for surgical-site infection (odds ratio [OR] 14.01; 95% confidence interval [CI] 1.36-143.52; P = 0.024). Fifteen (15%) patients experienced elevated serum creatinine after surgery and the median time to creatinine elevation was 5 days postoperatively (range 3-15 days). In multivariant analyses, only age of of 58 years or more was found as a significant factor for the elevation of serum creatinine (OR 6.96; 95% CI 1.42-32.81; P = 0.014). CONCLUSION: Our results showed that the presence of multiple metastases increased the risk of grade III-IV complications and age of 58 years or more was the leading risk factor for renal complications. However, we could not find a relation between postoperative complications and oncologic outcomes. HIPEC seems to be a safe approach in experienced hands.

Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study.

Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.

Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High-Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001).

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high-intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high-intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high-intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high-intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high-intermediate- and high-risk endometrial cancer cases.

European Society of Gynaecological Oncology quality indicators for the surgical treatment of endometrial carcinoma.

BACKGROUND: Quality of surgical care as a crucial component of a comprehensive multi-disciplinary management improves outcomes in patients with endometrial carcinoma, notably helping to avoid suboptimal surgical treatment. Quality indicators (QIs) enable healthcare professionals to measure their clinical management with regard to ideal standards of care. OBJECTIVE: In order to complete its set of QIs for the surgical management of gynecological cancers, the European Society of Gynaecological Oncology (ESGO) initiated the development of QIs for the surgical treatment of endometrial carcinoma. METHODS: QIs were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for the identification of potential QIs and documentation of the scientific evidence, two consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians and patient representatives. QIs were defined using a structured format comprising metrics specifications, and targets. A scoring system was then developed to ensure applicability and feasibility of a future ESGO accreditation process based on these QIs for endometrial carcinoma surgery and support any institutional or governmental quality assurance programs. RESULTS: Twenty-nine structural, process and outcome indicators were defined. QIs 1-5 are general indicators related to center case load, training, experience of the surgeon, structured multi-disciplinarity of the team and active participation in clinical research. QIs 6 and 7 are related to the adequate pre-operative investigations. QIs 8-22 are related to peri-operative standards of care. QI 23 is related to molecular markers for endometrial carcinoma diagnosis and as determinants for treatment decisions. QI 24 addresses the compliance of management of patients after primary surgical treatment with the standards of care. QIs 25-29 highlight the need for a systematic assessment of surgical morbidity and oncologic outcome as well as standardized and comprehensive documentation of surgical and pathological elements. Each QI was associated with a score. An assessment form including a scoring system was built as basis for ESGO accreditation of centers for endometrial cancer surgery.

European Society of Gynaecological Oncology guidelines for the peri-operative management of advanced ovarian cancer patients undergoing debulking surgery.

The European Society of Gynaecological Oncology (ESGO) developed and established for the first time in 2016, and updated in 2020, quality indicators for advanced ovarian cancer surgery to audit and improve clinical practice in Europe and beyond. As a sequela of the continuous effort to improve oncologic care in patients with ovarian cancer, ESGO issued in 2018 a consensus guidance jointly with the European Society of Medical Oncology addressing in a multidisciplinary fashion 20 selected key questions in the management of ovarian cancer, ranging from molecular pathology to palliation in primary and relapse disease. In order to complement the above achievements and consolidate the promoted systemic advances and surgical expertise with adequate peri-operative management, ESGO developed, as the next step, clinically relevant and evidence-based guidelines focusing on key aspects of peri-operative care and management of complications as part of its mission to improve the quality of care for women with advanced ovarian cancer and reduce iatrogenic morbidity. To do so, ESGO nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of ovarian cancer (18 experts across Europe). To ensure that the guidelines are evidence based, the literature published since 2015, identified from a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 117 independent international practitioners in cancer care delivery and patient representatives.

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

OBJECTIVE: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded. RESULTS: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months). CONCLUSIONS: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.

Feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer during COVID-19 pandemic.

OBJECTIVE: This study aims to evaluate the effect of the COVID-19 pandemic and related restrictions on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer. METHODS: We retrospectively evaluated ovarian cancer patients who underwent HIPEC following complete cytoreductive surgery performed during the outbreak of the COVID-19 pandemic in three different centers specializing in gynecological oncology. All patients who underwent cytoreduction plus HIPEC for a primary, interval, and recurrent surgery were evaluated. Primary outcomes was postoperative 30-day morbidity and mortality. The secondary outcome was infection of patient and/or related staff with COVID-19 during the perioperative or early postoperative period. RESULTS: We performed a total of 35 HIPEC procedures during the pandemic: 15 (42.9%) patients underwent primary/interval surgery, while 20 (57.1%) patients had recurrent disease. Grade 3-4 complications occurred in one patient (2.9%) (chronic renal failure), while mortality did not occur in any patient. Neither the patients nor related staff were infected with the coronavirus during the perioperative or early postoperative period. One patient, who was diagnosed with COVID-19 pneumonia on postoperative day 80 died from the infection. Another patient died on postoperative day 85 due to progressive ovarian cancer, a disorder in vital functions, and organ failure. CONCLUSION: HIPEC during the COVID-19 pandemic seems a safe and feasible procedure, with acceptable morbidity and mortality rates. Careful selection of patients is important and precautions should be taken before the procedure.

Comparison of two intraoperative examination methods for the diagnosis of sentinel lymph node metastasis in clinically early stage endometrial cancer: A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-003).

OBJECTIVE: This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. STUDY DESIGN: Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. RESULTS: Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. CONCLUSION: Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.