Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Best original research presented at the 24th European Congress on Gynaecological Oncology-Best of ESGO 2023.

The 'Best of ESGO 2023' manuscript comprises a compilation of the best original research presented during the European Society of Gynaecologic Oncology annual congress held in Istanbul between September 28 and October 1, 2023. Out of 1030 submitted abstracts, 33 studies presented during the Best Oral Sessions, Mini Oral Sessions, and Young Investigator Session were selected by the ESGO Abstract Committee and the European Network of Young Gynae Oncologists (ENYGO) authors. There was a strong focus on surgical de-escalation, immunotherapy, maintenance therapy, and molecular profiling in gynecologic oncology. With this manuscript, ENYGO and ESGO aim to disseminate the valuable research results to readers interested in our field.

Impact of adjuvant treatments and risk factors on survival in 2023 FIGO stage IIB endometrial cancer patients: Turkish Gynecologic Oncology Group Study.

OBJECTIVE: The aim of this study was to investigate the impact of adjuvant treatments, factors influencing recurrence, and survival data in patients with 2023 International Federation of Gynecology and Obstetrics (FIGO) stage IIB endometrial cancer. METHODS: A retrospective analysis was conducted on patients with endometrial cancer who underwent surgery between 2005 and 2022 at seven different centers in Turkey. Demographic, clinicopathological, and survival data were collected and analyzed. RESULTS: Among 7323 patients, 565 (7.7%) were classified as 2023 FIGO stage IIB based on pathological results. Of 565 patients, 214 were followed without receiving adjuvant treatment, while 335 (95.4%) received adjuvant radiotherapy, and 16 (4.6%) received radiotherapy and chemotherapy. The locoregional recurrence rate was higher in patients with a tumor size >4 cm (p=0.038) and myometrial invasion >50% (p=0.045). In patients with distant metastasis, the recurrence rate was lower in those with myometrial invasion <50% compared with myometrial invasion ≥50% (p=0.031). The impact of adjuvant treatment on endometrial cancer patients revealed no significant differences for both disease free survival (p=0.85) and overall survival (p=0.54). Subgroup analyses showed that in patients with deep myometrial invasion, adjuvant treatment was associated with a significant increase in overall survival (p=0.044), but there was no effect on disease-free survival (p=0.12). CONCLUSIONS: Patients with stage IIB endometrial cancer with myometrial invasion ≥50% were more likely to have locoregional and distant metastases. Adjuvant radiotherapy or chemoradiotherapy did not demonstrate an overall survival benefit in these patients.

Role of adjuvant therapy in intermediate-risk cervical cancer patients - Subanalyses of the SCCAN study.

OBJECTIVE: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. METHODS: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. RESULTS: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; PDFS = 0.365) and overall survival (88.7% and 89.0%; POS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: PDFS = 0.365; POS = 0.282). CONCLUSION: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy.

Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study.

BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). CONCLUSION: For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.

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.

The expression of programmed death-ligand 1 and programmed death-ligand 2 in endometrial carcinosarcoma: Correlation with mismatch repair protein expression status, tumor-infiltrating lymphocyte infiltration, and clinical outcomes.

BACKGROUND: Endometrial carcinosarcomas have high malignant potential with a high recurrence rate and poor prognosis. Immunotherapy may be a promising treatment option. The aim of this study is to evaluate the expression of PD-L1/PD-L2 and its relationship to mismatch repair (MMR) protein status and tumor-infiltrating lymphocyte (TIL) density. METHODS: We performed immunohistochemical analyses of PD-L1 (clone 22C3), PD-L2 (clone TY25), MSH-2, MSH-6, PMS-2, and MLH-1 in 77 tumors. We count TILs using CD8 antibody. Clinicopathologic features were recorded and statistically correlated with immunohistochemical results. Kaplan-Meier analyses were used to analyze the prognosis. RESULTS: While PD-L1 positivity was seen more commonly in MMR protein deficient tumors (p = 0.010), PD-L2 positivity was seen more commonly in MMR protein proficient tumors (p = 0.003). PD-L1 positivity was also found to be more common in carcinosarcoma with high TIL infiltration. PD-L2 positivity was associated with decreased overall survival (OS) rates (p = 0.043, p = 0.043, respectively), whereas the PD-L1 positivity and TIL density were not significantly associated with OS rate. The OS rate of patients with MMR protein proficient tumors was significantly lower compared with those with MMR protein deficient tumors (p = 0.042). The lower TILs infiltration was associated with a shorter disease-free survival (DFS) rate. PD-L1 and PD-L2 positivity did not affect the DFS rate. CONCLUSIONS: PD-L1/PD-L2 might be a better target for immunotherapy in endometrial carcinosarcoma. PD-L2 positivity was also associated with a worse clinical outcome in patients with endometrial carcinosarcoma, suggesting that PD-L2 status can be used to predict clinical behavior. Further studies are needed to elucidate the relationship between PD-L1/PD-L2 expression and therapeutic response.

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.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Factors associated with the involvement of lymph nodes in low-grade serous ovarian cancer.

BACKGROUND AND OBJECTIVES: Evaluating nodal metastases in low-grade serous ovarian cancer (LGSOC) patients. METHODS: Women with LGSOC who had undergone primary cytoreductive surgery comprising systematic pelvic-paraaortic lymphadenectomy were included. Data were obtained retrospectively from 12 oncology centers. RESULTS: One hundred and forty-eight women with LGSOC who had undergone comprehensive surgical staging were included. Seventy-one (48.0%) patients had metastatic lymph nodes. Preoperative serum CA-125 levels of ≥170 U/ml (odds ratio [OR]: 3.84; 95% confidence interval [CI]: 1.22-12.07; p = 0.021) and presence of lymphovascular space invasion (LVSI) (OR: 13.72; 95% CI: 3.36-55.93; p < 0.001) were independent predictors of nodal metastasis in LGSOC. Sixty (40.5%) patients were classified to have apparently limited disease to the ovary/ovaries. Twenty (33.3%) of them were upstaged after surgical staging. Twelve (20.0%) had metastatic lymph nodes. Presence of LVSI (OR: 12.96; 95% CI: 1.14-146.43; p = 0.038) and preoperative serum CA-125 of ≥180 U/ml (OR: 7.19; 95% CI: 1.35-38.12; p = 0.02) were independent predictors of lymph node metastases in apparent Stage Ⅰ disease. CONCLUSIONS: Clinicians may consider to perform a reoperation comprising systematic lymphadenectomy in patients who had apparently limited disease to the ovary/ovaries and had not undergone lymphadenectomy initially. Reoperation may be considered particularly in patients whose preoperative serum CA-125 is ≥180 U/ml and/or whose pathological assessment reported the presence of LVSI.

Clinicopathologic and Prognostic Significance of CD47 Expression and Tumor-associated Macrophages in Endometrial Carcinoma.

Tumor-associated macrophages (TAMs) influence cancer progression. CD47 is an antiphagocytic molecule aiding tumor resistance against host immune surveillance. The relationship between CD47 expression and TAM-related microenvironment in endometrial carcinoma (EC) is poorly understood. The expression and prognostic significance of CD47 and CD163-labeled TAMs in 165 EC cases was assessed with CD47 and CD163 immunohistochemical studies. CD47 expression was found in 156/165 (94.6%) cases. CD47 expression was significantly higher in nonendometrioid carcinomas. CD47 overexpression was associated with histologic grade. High epithelial and stromal TAMs counts were also associated with high tumoral CD47 expression. High epithelial, stromal, and margin TAMs counts were associated with higher histologic grade and lymphovascular invasion. Epithelial TAMs counts were higher in patients with nonendometrioid carcinomas (P=0.0001) and cases with recurrence (P=0.018). High stromal TAMs counts were associated with deeper myometrial invasion (P=0.017) and the presence of distant metastasis (P=0.024). The counts of margin TAMs was significantly correlated with the depth of myometrial invasion, lymphovascular invasion, FIGO stage, lymph node metastases, distant metastasis, and recurrence (P=0.0001, 0.0001, 0.004, 0.005, 0.014, and 0.04, respectively). CD47 expression was not associated with overall survival (OS) and progression-free survival. However, high epithelial and stromal TAM counts were associated with shorter OS. Besides, high epithelial and margin TAM counts were associated with shorter progression-free survival. Furthermore, increased stromal and margin TAM counts were determined to be an independent prognostic marker of reduced OS. TAM count is, therefore, a significant prognostic factor in EC and the CD47 assessment has potential benefit for future clinical use.

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.

Survival impact of number of removed para-aortic lymph nodes in stage I epithelial ovarian cancer.

PURPOSE: The survival effect of presence or absence of lymphadenectomy in early-stage epithelial ovarian cancer (EOC) was priorly shown but the effect of number of removed lymph nodes kept in background. We aimed to evaluate the survival impact of number of removed lymph nodes and their localizations in stage I EOC. METHODS: This study included 182 patients. The best cut-off levels for number of pelvic and para-aortic lymph nodes (PaLN) were 24 and 10, respectively. Univariate and multivariate survival analyses were performed for these cut-offs and other prognostic factors. RESULTS: The median age of the patients was 49. The median number of removed pelvic and paraartic lymph nodes were 29 and 9, respectively. The median overall (OS) and progression-free survival (PFS) were 67 and 50 months, respectively. The 5-year OS rate was 89.6%. Recurrence occured in 24 (19.5%) patients. In univariate analyses tumor grade (p: 0.005), pelvic LN number (p: 0.041) and PaLN number (p: 0.004) were the factors that were significantly associated with PFS. Tumor grade and PaLN number were independently and significantly associated with PFS in multivariate analyses (p: 0.015 and p: 0.017, respectively). In OS analyses, age, tumor grade, presence of LVI, number of pelvic and PaLNs were the significantly associated factors (p < 0.05 for all). In multivariate analyses, age and PaLN number were independently and significantly associated with OS (p: 0.011 and p: 0.021, respectively). CONCLUSIONS: The number and localizations of removed lymph nodes may have a survival affect in stage I EOC. We also think that this study may constitute a kernel point for larger prospective series on lymph node number and lymphatic regions.

Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies.

AIM: This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). MATERIALS AND METHODS: The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. RESULTS: The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. CONCLUSION: Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.

Survival in recurrent ovarian cancer patients before and after the bevacizumab era: an observational single-centre study.

A retrospective observational study was carried out in Baskent University School of Medicine, Ankara, Turkey. Recurrent ovarian cancer patients treated between 2007 and 2017 were divided into two groups according to their bevacizumab status. The primary endpoints were overall survival (OS) and safety. Three hundred and ninety-six patients enrolled in this study, 200 (50.5%) received bevacizumab while 196 (49.5%) patients never received bevacizumab. The median follow-up time was 48.2 and 47.6 months, respectively. The 5-year OS was 61% and 46%, respectively (p=.007). In multivariate analysis, only platinum-sensitivity (HR: 3.75, 95% CI: 3.0-5.32; p<.001) was identified as independent prognostic factors. In subgroup analyses according to platinum status, bevacizumab did not affect the 5 year OS in platinum sensitive patients (64% versus 68% p=.28) but increased survival in platinum resistant patients (36% versus 44%, p=.00). The rate of grade III-IV haematologic toxicities was 13.7% in the bevacizumab group and 11% in the other group (p=.6).Impact StatementWhat is already known on this subject? Bevacizumab increases the progression-free survival in platinum-sensitive and resistant recurrent ovarian cancer patients without changing overall survival.What do the results of this study add? Bevacizumab did not affect OS in platinum sensitive recurrent ovarian cancer patients however improved OS in platinum resistant patients with mild toxicity.What are the implications of these findings for clinical practice and/or further research? This study emphasised the crucial role of bevacizumab in the treatment of recurrent ovarian cancer patients.

Incidence of unexpected leiomyosarcoma in a Turkish province: a retrospective multi-centre study in a low income setting.

The aim of the current study was to estimate the incidence of unexpected leiomyosarcoma (LMS) in patients who underwent surgery due to leiomyomas in Konya province, and to contribute to the literature discussing comparisons with similar studies. The digital archives of eight high-volume hospitals were studied for surgeries performed due to leiomyomas between January 2012 and January 2019, and leiomyosarcoma incidence was calculated based on the data obtained. Twenty-one patients in 3703 cases were found to have unexpected leiomyosarcoma, which means we can expect one leiomyosarcoma in 176 (0.56%) surgeries. Six more malignant tumours were detected among the remaining cases. Thus, our study estimated the incidence of unexpected leiomyosarcoma as 1/176 (0.56%), which is higher than most of the studies in the literature justifying the debate started by the FDA in 2014. As the tumour biology is not yet clear, and the incidence of unexpected leiomyosarcoma tends to be so high, the key focus must be to try to detect uterine leiomyosarcomas preoperatively for robust patient care.IMPACT STATEMENTWhat is already known on this subject? The incidence of unexpected leiomyosarcoma varies widely from 1/498 to 1/8300 depending on the study method and the type of procedure, and there is still controversy, even after the FDA statement that led to a major restriction in laparoscopic surgeries due to concerns about inadvertent morcellation of leiomyosarcomas.What do the results of this study add? To the best of our knowledge, the current study found the highest incidence of unexpected leiomyosarcoma, and consequently a serious evaluation of all patients undergoing surgery due to leiomyomas preoperatively considering a leiomyosarcoma candidate is recommended.What are the implications of these findings for clinical practice and/or further research? Studies on tumour biology and novel markers must be supported for accurate preoperative diagnosis of leiomyosarcoma.

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.

Low-grade endometrial stromal sarcoma: A Turkish uterine sarcoma group study analyzing prognostic factors and disease outcomes.

OBJECTIVE: To investigate factors associated with refractory disease, recurrence, or death as well as disease-free survival (DFS) and overall survival (OS) in low-grade endometrial sarcoma (LGESS). METHODS: A multi-institutional, retrospective study was conducted in a total of 124 patients, who received a curative-intent surgery. The exclusion criteria were as follows: i) history of any other invasive disease; ii) neoadjuvant therapy; iii) fertility sparing surgery; iv) a different diagnosis after review of the slides. RESULTS: All patients underwent hysterectomy, 96% had bilateral salpingo-oophorectomy, and 65% had lymphadenectomy. Twelve (14.8%) of 81 patients undergoing lymphadenectomy had lymph node (LN) metastasis. Of those, 8 (9.8%) had pelvic LN metastasis whereas 4 (5.6%) had isolated paraaortic LN metastasis. Six of 8 (75%) patients with positive pelvic LNs had concurrent paraaortic LN metastasis. Among 124 patients, 3 patients (2.4%) had refractory disease following primary therapy. During a median follow-up of 45.5 months, 27 (22.3%) of 121 patients who achieved complete remission after primary therapy developed recurrence, and 10 patients (8.1%) died of disease. The 3-year DFS and OS were 76.9% and 93.8%, respectively. Stage was the sole independent prognostic factor in the whole cohort. When analyzing factors within subgroups of stage I and stage ≥II, there was no significant prognostic factor for stage I; however, lymphadenectomy and adjuvant chemotherapy were significantly associated with disease outcomes for stage ≥II. While lymphadenectomy was related with improved DFS, chemotherapy was associated with poor DFS and OS. CONCLUSION: The risk of LN metastasis at pelvic as well as paraaortic lymphatic basins is not negligible to omit lymphadenectomy in stage ≥II LGESS. Moreover, lymphadenectomy provides significant DFS advantage in patients with extrauterine disease.

Perioperative SARS-CoV-2 infection among women undergoing major gynecologic cancer surgery in the COVID-19 era: A nationwide, cohort study from Turkey.

OBJECTIVE: The objective of this study was to determine the rate of perioperative SARS-CoV-2 infection among gynecologic cancer patients undergoing major surgery. METHODS: The database of the Turkish Ministry of Health was searched in order to identify all consecutive gynecologic cancer patients undergoing major surgery between March 11, 2020 and April 30, 2020 for this retrospective, nationwide, cohort study. The inclusion criteria were strictly founded on a final histopathological diagnosis of a malignant gynecologic tumor. COVID-19 cases were diagnosed by reverse transcriptase- polymerase chain reaction testing for SARS-CoV-2. The rate of perioperative SARS-CoV-2 infection and the 30-day mortality rate of COVID-19 patients were investigated. RESULTS: During the study period, 688 women with gynecologic cancer undergoing major surgery were identified nationwide. The median age of the patients was 59 years. Most of the surgeries were open (634/688, 92.2%). There were 410 (59.6%) women with endometrial cancer, 195 (28.3%) with ovarian cancer, 66 (9.6%) with cervical cancer, 14 (2.0%) with vulvar cancer and 3 (0.4%) with uterine sarcoma. The rate of SARS-CoV-2 infections confirmed within 7 days before or 30 days after surgery was 46/688 (6.7%). All but one woman was diagnosed postoperatively (45/46, 97.8%). The rates of intensive care unit admission and invasive mechanical ventilation were 4/46 (8.7%) and 2/46 (4.3%), respectively. The 30-day mortality rate was 0%. CONCLUSION: In the COVID-19 era, gynecologic cancer surgery may be performed with an acceptable rate of perioperative SARS-CoV-2 infection if the staff and the patients strictly adhere to the established infection control measures.

Impact of cytoreductive surgery on survival of patients with low-grade serous ovarian carcinoma: A multicentric study of Turkish Society of Gynecologic Oncology (TRSGO-OvCa-001).

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). METHODS: Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. RESULTS: Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. CONCLUSIONS: The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.