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Objective: The aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer., Methods: Individual data from three phase III, randomized controlled trials (AGO-OVAR 11, AGO-OVAR 12, and AGO-OVAR 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were classified as ever user if the specific co-medication was documented at least once during the trial, and were compared with never users as controls. Association of co-medications and outcomes were adjusted for potential confounders (age, International Federation of Gynecology and Obstetrics stage, histology, residual disease after surgery, Eastern Cooperative Oncology Group (ECOG) performance status, body mass index, Charlson Comorbidity Index, and assigned treatment within the trial) in multivariate Cox regression analyses., Results: Overall, n=2857 patients were included. Ever users were: 100 patients received metformin (3.5%), 226 patients received statins (7.9%), and 475 (16.6%) patients received beta blockers (n=391 selective beta blockers; 84 non-selective beta blockers) as co-medication. There were no significant differences regarding the baseline characteristics except that ever users were significantly older, more obese, and had more comorbidities, according to the Charlson Comorbidity Index, compared with controls. Multivariate analyses for progression free survival and overall survival revealed neither a significant impact of metformin on survival (progression free survival hazard ratio (HR) 0.94, 95% confidence interval CI 0.69 to 1.29, p=0.7; overall survival HR 0.82, 95% CI 0.58 to 1.17, p=0.28) nor for statins (progression free survival HR 0.98, 95% CI 0.82 to 1.18, p=0.87; overall survival HR 0.91, 95% CI 0.74 to 1.12, p=0.37). In contrast, ever users of selective beta blockers had a significantly higher risk for recurrence and death (progression free survival HR 1.22, 95% CI 1.05 to 1.41, p=0.009; overall survival HR 1.25 95% CI 1.06 to 1.47, p=0.009)., Conclusions: In this analysis, co-medication with metformin or statins had no significant impact on survival in patients with primary ovarian cancer. In contrast, co-medication with a beta blocker was associated with worse survival. However, whether this observation is related to the underlying condition rather than a direct negative impact on tumor biology remains unclear., Competing Interests: Competing interests: DD: honoraria: AstraZeneca, GSK, Intuitive, KLS Martin, Merck Sharp & Dohme (MSD); travel/accommodation/expenses: AstraZeneca; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Eisai, GSK, KLS Martin, MSD, PharmaMar, Seagen. FH: personal fees and non-financial support: AstraZeneca, Roche, Tesaro, GSK, Clovis; personal fees: Zailabs and PharmaMar, outside the submitted work. JF: honoraria: Medupdate, Decision Resources, Simon-Kucher and Partners, Juniper, Bionest Partner, Vox Bio, Axiam Healthcare Strategies, Prosapient, Lilly, MedPartners; research funding: Roche Pharma AG, GSK/Tesaro; travel/accommodation/expenses: Roche Pharma AG. PH: grants, personal fees and non-financial support: Astra Zeneca, GSK; grants and personal fees: Roche, MSD, Clovis, Immunogen; personal fees: Sotio, Stryker, Zai Lab, Mersana, Miltenyi; grants: Boehringer lngelheim, Medac, Genmab, Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft, outside the submitted work. PW: Advisory Board Member and received honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche Pharma, Eisai, Clovis, GSK, Daiichi Sankyo. MRM: honoraria: Astra Zeneca, Eisai, Genmab, GSK, Mersana, Takeda, Zailab; travel/accommodation/expenses: AstraZeneca, GSK, Takeda; Advisory Board: Allarity Therapeutics, Astra Zeneca, Biontech, Daiichi-Sankyo, Eisai, Genmab, GSK, lmmunogen, Incyte, Merck/MSD, Mersana, Regeneron, Zailab; Chairman (2020-2022) of the European Network of Gynaecological Oncology Trials group; Vice-President of the European Society of Gynaecological Oncology; Faculty member of the European Society of Medical Oncology; Scientific Chair of the International Gynecologic Cancer Society; stock options: Karyopharm Therapeutics, Sera Prognostics. IRC: grants/contracts: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD; honoraria: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, PharmaMar, Seagen, ESAI, Novartis; travel/accommodation/expenses: Roche, GSK, Astra Zeneca, PharmaMar, MSD; Data Safety Monitoring Board/Advisory Board: Clovis, Deciphera, AdaptImmune, Sutro, Immunogen. GS: grants: MSD Italia S.r.l; consulting fees: Tesaro Bio Italy S.r.l, Johnson & Johnson; payment for expert testimony: Clovis Oncology Italia S.r.l; NC: grants: GSK, Astrazeneca; consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche; honoraria: AstraZeneca, Novartis, Clovis Oncology,GSK, MSD/Merck; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche. AO: Grants to institution: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc., Eisai Ltd, F. Hoffmann-La Roche Ltd, Regeneron Pharmaceuticals, lmmunogen Inc, Merck, Sharp & Dohme de Esparsia SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; consulting fees and honoraria: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, lmmunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; travel/accommodation/expenses: AstraZeneca, PharmaMar, Roche; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; JS: study funding to institution: GSK, AstraZeneca, MSD, Clovis, Tesaro; consulting fees: GSK, Astra Zeneca, Tesaro, MSD, Elisei, Clovis, Riemser, Roche; travel/accomodation/expenses: Roche; Data Safety Monitoring Board/Advisory Board: GSK, PharmaMar, Novocure, Astra Zeneca, Clovis, GSK, Tesaro; ESGO Faculty; NOGGO President; PARSGO President. KL: grants: GSK; honoraria: Eisai; Data Safety Monitoring Board/Advisory Board: Eisai, MSD, Nycode, Astra Zeneca, GSK. CL: honoraria: IMSD, GSK, Eisai, Clovis Oncology; travel/accommodation/expenses: MSD, GSK; Data Safety Monitoring Board/Advisory Board: GSK. ME: stock/stock options: GSK. AdB: honoraria: Zodiac, AMGEN, GSK/Tesaro; Data Safety Monitoring Board/Advisory Board: AstraZeneca/MSD, AMGEN, Pfizer, GSK/Tesaro. All other authors declare no competing interests., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of first-line poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is increasing in advanced ovarian cancer. Understanding the efficacy of first subsequent therapy (FST) in patients experiencing disease progression in the first-line setting is important to optimize postprogression treatments. We evaluated the efficacy of FST in patients from PAOLA-1/ENGOT-ov25 (NCT02477644) who received first-line olaparib maintenance., Patients and Methods: This post hoc analysis evaluated the efficacy of subsequent chemotherapy following disease progression by assessing time from FST to second subsequent therapy (SST) according to whether progression occurred during versus after first-line olaparib maintenance and FST type. A multivariate Cox model was used in the olaparib plus bevacizumab arm to identify prognostic factors influencing the efficacy of subsequent chemotherapy., Results: Of 806 randomized patients, 544 (67.5%) progressed and received subsequent chemotherapy. The median time from FST to SST was shorter in patients in the olaparib plus bevacizumab arm who progressed during first-line olaparib maintenance (6.1 months) than in those who progressed after first-line olaparib maintenance (11.4 months). Multivariate analysis indicated that progression after (versus during) first-line olaparib maintenance influenced time from FST to SST (hazard ratio 0.65, 95% confidence interval 0.50-0.84; P = 0.0011) independently of platinum-free interval or clinical risk. Among patients who progressed and received platinum-based chemotherapy with a PARP inhibitor as FST, the efficacy of subsequent therapies was also dependent on whether progression occurred during versus after first-line olaparib maintenance., Conclusions: These results suggest that the timing of disease progression relative to first-line olaparib maintenance may impact the efficacy of subsequent platinum-based chemotherapy. Although results should be interpreted with caution, across all subgroups, including patients who received platinum-based chemotherapy with PARP inhibitor rechallenge as FST, the median time from FST to SST was longer if progression occurred after versus during first-line olaparib maintenance., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial., Methods: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression. Patient-reported outcomes, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Endometrial Cancer Module, were prespecified secondary endpoints. A mixed model for repeated measures analysis, a prespecified exploratory analysis, was conducted to generate least-squares means to compare between-treatment differences while adjusting for correlations across multiple time points within a patient and controlling for the baseline value. Results are provided with 2-sided, nominal p values., Results: Of 494 patients enrolled, 118 were mismatch repair-deficient/microsatellite instability-high. In this population, mean change from baseline to end of treatment showed visual improvements in global quality of life (QoL), emotional and social function, pain, and back/pelvis pain for dostarlimab+carboplatin-paclitaxel. Meaningful differences (least-squares mean [standard error]) favoring the dostarlimab arm were reported for change from baseline to end of treatment for QoL (14.7 [5.45]; p=0.01), role function (12.7 [5.92]); p=0.03), emotional function (14.3 [4.92]; p<0.01), social function (13.5 [5.43]; p=0.01), and fatigue (-13.3 [5.84]; p=0.03)., Conclusions: Patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer receiving dostarlimab+carboplatin-paclitaxel demonstrated improvements in several QoL domains over patients receiving placebo+carboplatin-paclitaxel. The observed improvements in progression free survival and overall survival while improving or maintaining QoL further supports dostarlimab+carboplatin-paclitaxel as a standard of care in this setting., Trial Registration: ClinicalTrials.gov NCT03981796., Competing Interests: Competing interests: GV reports consulting fees from GSK; honoraria from AstraZeneca, GSK, and MSD; travel support from AstraZeneca and PharmaMar; participation in advisory boards for AstraZeneca, Eisai, GSK, and MSD. MAP reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca. SH reports consulting fees from AstraZeneca, Eisai, GSK, and MSD and honoraria from AstraZeneca and GSK. EMM reports advisory board meeting fees from AstraZeneca, GSK, and Tempus; honoraria from OncLive and Opinions in Gyn Malignancies; and support for attending meetings from Opinions in Gyn Malignancies and OncLive. ZN reports honoraria from Sofmedica, AstraZeneca, and MSD; support for attending meetings from Sofmedica and Preglem; participation on a data safety monitoring board or advisory board for AstraZeneca and Richter Gedeon; stock options from Richter Gedeon; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from AstraZeneca. RH reports honoraria from GSK, AstraZeneca, Clovis Oncology, Eisai, and Merck. DD reports receiving consulting fees from AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; honoraria for advisory roles from Roche, AstraZeneca, GSK/Tesaro, Intuitive Surgical, KLS Martin, MSD, PharmaMar, and Seagen; and travel support from AstraZeneca. TM reports honoraria from Immunogen. LG reports institutional grants from Alkermes, AstraZeneca, Clovis Oncology, Esperas, IMV, ImmunoGen, Karyopharm, MSD, Mersana, Novocure, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK. BA reports honoraria from AstraZeneca, Eisai, GSK, MSD, Norartis, and Roche; support for attending meetings from AstraZeneca, GSK, and Roche; participation on a data safety monitoring board or advisory board for Eisai, GSK, MSD, Roche, and Sanofi Aventis. RG reports participation on a data safety monitoring board or advisory board for Pionyr Pharmaceuticals and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Bausch+Lomb. NC reports advisory board fees for Aadii, GSK, Kartos, Novita Pharmaceuticals, Tarveda Therapeutics, Toray, Umoja, and Zentalis. BJM reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers’ bureau honoraria from AstraZeneca, Clovis Oncology, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. TJH reports personal consulting fees from Aadi, AstraZeneca, Caris, Clovis Oncology, Eisai, Epsilogen, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen; participation on a data safety monitoring board or advisory board for Corcept; and leadership role on the GOG Foundation Board and President of GOG Partners. AS reports royalties as an UptoDate reviewer. BP reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, SeaGen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, I-Mab Biopharma, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, and Toray; support for attending meetings from GOG Foundation; advisory board fees from Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab Biopharma, Lilly, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutics; and noncompensated leadership fees from NYOB Society Secretary, SGO Clinical Practice Committee Chair, and SGO COVID-19 Taskforce Co-Chair. AAS reports support paid to her institution from GSK for the present IGCS abstract; institutional grant support from AbbVie, Aravive, AstraZeneca, Clovis Oncology, Eisai, Ellipses, I-Mab Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Roche/Genentech, Seagen, TapImmune, Tesaro/GSK, and VBL Therapeutics; honoraria from @Point of Care Clinical Care Options Curio Science, Peerview, Bio ASCEND, RTP, GOG Foundation (Highlight reel), and GOG Foundation Symposium; patent issued for 'blood based biomarkers in ovarian cancer'; noncompensated participation on a data safety monitoring board/advisory board from AstraZeneca, Clovis Oncology, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, and OncoQuest; uncompensated leadership roles with SGO, AAOGF, and NRG and compensated role from GOG; receipt of medical writing support from AstraZeneca; and uncompensated Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio). DC reports consultant fees from AstraZeneca and GSK and honoraria from AstraZeneca, GSK, Seagen/Genmab, and Immunogen. MRM reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, and Zai Lab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors). DB reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365. AMT, KPP, EF, OZ, LML, IP, and SS have nothing to disclose. OM, VV, and JG are employees of GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

The presentation of the results of the prospective randomized international multicenter GCIG INTERLACE trial at the 2023 congress of the European Society of Medical Oncology (ESMO) is likely to change the therapy for locally advanced cervical cancer. In the GCIG INTERLACE trial, six cycles of neoadjuvant chemotherapy administered weekly and consisting of carboplatin AUC2 and paclitaxel 80 mg/m 2 followed by definitive radiochemotherapy with pelvic radiotherapy (40 - 50.4 Gray) and cisplatin (40 mg/m 2 once a week for 5 weeks) and brachytherapy (total dose EQD2 at least 78 Gy at point A) (experimental arm) were compared with definitive radiochemotherapy alone (standard arm) in patients with locally advanced cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] 2008 stage IB1/node positive, IB2, II, IIIB and IVA) and was found to be significantly superior with significantly longer recurrence-free survival (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.64 - 0.91; p = 0.013) and significantly longer overall survival rates (HR 0.61; 95% CI: 0.40 - 0.91; p = 0.04) after 5 years' follow-up. After considering the results of the GCIG INTERLACE trial published at the congress, the Uterus Commission of the AGO is of the opinion that neoadjuvant chemotherapy with carboplatin AUC2 and paclitaxel 80 mg/m 2 d1, q7, x6 may be offered to patients with locally advanced cervical cancer (FIGO stage IB1/node positive, IB2, II, IIIB and IVA) in addition to the current standard therapy after the patient has been informed about the risks, with the decision taken on a case-by-case basis. However, before this approach can be discussed at guideline level or defined as the new therapy standard, it will be necessary to wait until the data from the full publication are available., Competing Interests: Conflict of Interest/Interessenkonflikt The authors state that they have no conflict of interest./ Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The presentation of the results of the prospective randomized international multicenter study AGO-OP.8 - CCTG CX.5 - SHAPE at the annual conference of the American Society of Clinical Oncology (ASCO) in 2023 will affect the surgical treatment of early-stage cervical cancer. In the SHAPE study, simple total hysterectomy (experimental arm) was found to be non-inferior to radical hysterectomy (standard arm) to treat patients with early-stage cervical cancer (FIGO stages [2018] IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm); after 3 years' follow-up the pelvic recurrence rate was 2.52% (experimental arm) compared to 2.17% (standard arm) with no statistically significant difference with regards to recurrence-free survival and overall survival rates. After weighing up the results of the SHAPE study published at the conference, the Uterus Organ Commission of AGO is of the opinion that, in addition to the use of radical hysterectomy to treat patients with invasive cervical cancer which is FIGO stage IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm, simple total hysterectomy may also be considered for primary surgical therapy on a case-by-case basis after suitable explanation of the associated risks. It will be necessary to wait for the data of the full publication before discussing whether this approach should be included in official guidelines and defining it as a new therapy standard., Competing Interests: Conflict of Interest/Interessenkonflikt The authors (T Fehm, MW Beckmann, D Denschlag, S Brucker, C Tempfer) state that they have no conflicts of interest relating to the contents of this publication. S Mahner is the German principal investigator of the SHAPE trial., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The publication of two large randomized studies - the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial and the NRG-GY018 trial - which investigated combining chemotherapy with immunotherapy to treat patients with primary advanced or recurrent endometrial cancer (EC) has transformed the clinical study landscape in terms of first-line therapy for affected patients and has set a new standard of therapy. In the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial, the addition of dostarlimab to standard chemotherapy with carboplatin and paclitaxel resulted in a significant and clinically relevant improvement of progression-free survival and overall survival in the overall population, a significant and clinically relevant improvement of progression-free survival and overall survival in the subgroup with dMMR/MSI-high tumors, and a significant and clinically relevant improvement of progression-free survival in the subgroup with pMMR/MSI-low tumors. In the NRG-GY018 trial, the addition of pembrolizumab to standard chemotherapy with carboplatin and paclitaxel resulted in a significant and clinically relevant improvement of progression-free survival in the group with dMMR tumors, and a significant and clinically relevant improvement of progression-free survival in the group with pMMR tumors. As expected, the effect in both trials was much more pronounced in the group of patients with dMMR/MSI-high tumors. According to the assessment of the Uterus Organ Commission of the AGO, all patients with dMMR/MSI-high tumors should receive chemoimmunotherapy and all patients with pMMR/MSI-low tumors who meet the inclusion criteria of the two trials discussed here may have chemoimmunotherapy. For dostarlimab this means: patients with EC recurrence who will not undergo surgery or radiotherapy, patients with stage IIIA, IIIB or IIIC1 disease and a measurable lesion postoperatively, patients with stage IIIA, IIIB or IIIC1 disease with histological findings of serous EC, clear-cell EC or carcinosarcoma with or without a measurable lesion postoperatively, and patients with stage IIIC2 or IV disease with or without a measurable lesion postoperatively. For pembrolizumab this means: patients with EC recurrence (except carcinosarcoma) who will not undergo surgery or radiotherapy, and patients with stage III or IVA disease (except carcinosarcoma) and a measurable lesion postoperatively or with stage IVB disease with or without a measurable lesion., Competing Interests: Conflict of Interest/Interessenkonflikt The authors state that they have no conflict of interests./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status., Patients and Methods: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis., Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms., Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure., Competing Interests: Disclosure IRC reports honoraria (personal) from AbbVie, Agenus, Advaxis, Bristol Myers Squibb (BMS), PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD), Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis; honoraria (institution) from GSK, MSD, Roche, and BMS; advisory/consulting fees from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis; research grant/funding (self) from MSD, Roche, and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca, and Merck Sereno; and travel support from Roche, AstraZeneca, and GSK. AL reports grants from AstraZeneca and Sanofi; consulting fees from Seattle Genetics; honoraria/reimbursement and advisory board fees from AstraZeneca; advisory board fees or continuing medical education from Ability Pharma, Biocad, Clovis Oncology, GSK, Medscape, Merck Serono, MSD, TouchCongress, and Zentalis; support for attending meetings and/or travel from AstraZeneca, Clovis Oncology, GSK, and Roche; and participation on a data safety monitoring board or advisory board for ARIEL4 and TROPHIMMUNE. SP reports honoraria from AstraZeneca, Roche, MSD, Pfizer, Tesaro, Clovis Oncology, GSK, and PharmaMar; and research funding (institution) from Roche, MSD, AstraZeneca, and Pfizer. AGM reports advisory/consultancy fees (personal) from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Eisai, Genmab, GSK, Hedera Dx, Illumina, ImmunoGen, MSD, Macrogenics, Mersana, Novartis, Oncoinvent, PharmaMar, Roche, Regeneron, Sotio, and Sutro; speaker bureau fees (personal) from AstraZeneca, Roche, GSK, MSD, Novocure, Takeda, Zai Lab, and Clovis; research grant/funding (institution) from Roche, Novartis, GSK, and Aravive; and steering committee member (personal) for MSD. CM reports honoraria/consulting fees (personal) from Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, and Seagen; participation on an advisory board from Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, and Seagen; and travel expenses from Roche and AstraZeneca. SN reports honoraria (self) from AstraZeneca, Chugai, Mochida, MSD, Takeda, and Terumo; and research grant (self) from AstraZeneca. IV reports consulting fees from Agenus, Akesobio, AstraZeneca, BMS, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Seagen, Sotio, Verastem Oncology, and Zentalis; contracted research funding (via KULeuven) from Oncoinvent AS; corporate sponsored research funding from Amgen and Roche; and accommodation and travel expenses from Karyopharm. NC reports research grants from AstraZeneca, PharmaMar, and Roche; honoraria for lectures from AstraZeneca, Tesaro, Novartis, Clovis Oncology, MSD, GSK, and Eisai; honoraria for advisory boards from Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GSK, Tesaro, Pfizer, BIOCAD, ImmunoGen, Mersana Therapeutics, Eisai, and OncXerna Therapeutics; and is a steering committee member on ESMO clinical guidelines and a scientific committee chair for Acto Onlus. JM reports honoraria from AstraZeneca and GSK. FS reports honoraria from AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology; and institutional financial support from Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. JS reports grants or contracts from Roche Pharma, AstraZeneca, Bayer, Clovis, GSK, Lilly, Tesaro, consulting fees from Tesaro, Merck, Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharma, GSK, MSD, Eisai, Novocure, Oncoinvent, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Tesaro, GSK, PharmaMar, AstraZeneca, Clovis, Bayer, Roche, PharmaMar, Vifor Pharma, Hexal AG, Novartis Pharma. DL reports consultancy fees (personal) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, Novartis, and Seagen; membership on an advisory board (personal) from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; research funding (institutional) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; and travel support from Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GSK. EMGA reports consulting fees from AstraZeneca–MSD, Clovis Oncology, GSK–Tesaro, PharmaMar, and Roche; speaker bureau/expert testimony honorarium from AstraZeneca–MSD, PharmaMar, Roche, GSK–Tesaro, and Clovis Oncology; and travel support from Roche, GSK–Tesaro, and Baxter. GB reports consulting or advisory board roles for AstraZeneca, Roche, and GSK; and has received funding for medical conferences from AstraZeneca, Roche, and GSK. CLP reports advisory/consultancy honoraria from Pfizer, AstraZeneca, Roche, and Daiichi–Sanko; and other travel/accommodation/medical congress expenses from Roche, Novartis, Pfizer, Pierre Fabre, and MSD. PB reports honoraria from Roche, AstraZeneca, and GSK; and congress and travel support from GSK and PharmaMar. AL reports advisory board fees from AstraZeneca, MSD, and Tesaro; speaker honoraria from Clovis Oncology and Roche; and participation in a medical congress for Novartis, Pfizer, MSD, Lilly, and Roche. AB reports honoraria for lectures and advisory boards from AstraZeneca, Roche, and Tesaro. JM reports advisory board fees (personal) from Daiichi Sankyo, Gilead, and Eli Lilly; and non-financial traveling facilities from Pfizer. AEB reports advisory board fees from AstraZeneca, MSD, and GSK; speaker honoraria from AstraZeneca and Olympus; and participation in a medical congress for PharmaMar and AstraZeneca. MR reports advisory board fees (personal) from AstraZeneca, GSK, and Immunocore; advisory board fees and research grant (personal/institution) from MSD; and research grant (institution) from BMS. TWPS reports honoraria (advisory role, expert testimony and lectures, participation in clinical trials, other financial relationships, e.g. travel) from AstraZeneca, Daiichi-Sankyo, Exact Sciences, Gilead, GSK, Lilly, MSD, NCO, Novartis, Pfizer, Roche, and Seagen. CD reports participation on a data safety monitoring board or advisory board for MSD, Eisai, and AstraZeneca. DD reports consulting or advisory roles (personal) for AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; travel expenses from AstraZeneca; and honoraria from Roche, AstraZeneca, GSK/Tesaro, MSD, Intuitive Surgical, and KLS Martin. BY reports consulting fees (personal) from MSD, AstraZeneca, GSK–Tesaro, Bayer, Roche–Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, and Myriad. EPL reports lecture fees, speaker’s bureau fees, and travel support from AstraZeneca, Tesaro, and Roche; lecture fees from Clovis Oncology, Incyte, and Pfizer; and is employed by ARCAGY Research. PH reports honoraria from AstraZeneca, Roche, Clovis Oncology, Stryker, MSD Oncology, Zai Lab, Lilly, Sotio, Eisai, and GSK; consulting/advisory roles from AstraZeneca, Roche, Tesaro, Merck, GSK, Clovis Oncology, and Immunogen; and research funding (institution) from AstraZeneca, Roche, Genmab, GSK, Immunogen, and Clovis Oncology. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The evidence-based (S3) guideline "Adult Soft Tissue Sarcomas" (AWMF Registry No. 032/044OL) published by the German Guideline Program in Oncology (GGPO) covers all aspects of sarcoma treatment with 229 recommendations. Representatives of all medical specialties involved in sarcoma treatment contributed to the guideline. This paper compiles the most important recommendations for surgeons selected by delegates from the surgical societies., Methods: A Delphi process was used. Delegates from the surgical societies involved in guideline process selected the 15 recommendations that were most important to them. Votes for similar recommendations were tallied. From the resulting ranked list, the 10 most frequently voted recommendations were selected and confirmed by consensus in the next step., Results: The statement "Resection of primary soft tissue sarcomas of the extremities should be performed as a wide resection. The goal is an R0 resection" was selected as the most important term. The next highest ranked recommendations were the need for a preoperative biopsy, performing preoperative MRI imaging with contrast, and discussing all cases before surgery in a multidisciplinary sarcoma committee., Conclusion: The evidence-based guideline "Adult Soft Tissue Sarcomas" is a milestone to improve the care of sarcoma patients in Germany. The selection of the top ten recommendations by surgeons for surgeons has the potential to improve the dissemination and acceptance of the guideline and thus improve the overall outcome of sarcoma patients., (© 2023. The Author(s).)

Objective: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease., Methods: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021., Results: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy., Conclusion: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer., Methods: In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m 2 plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability., Results: Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab., Conclusion: Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.

Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process. Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6. Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all of the authors are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

Background: Ovarian insufficiency is a major concern for long-term cancer survivors. Ovarian tissue cryopreservation for fertility preservation is an emerging technique that has proven successful over the past decade through transplantation of frozen-thawed ovarian tissue. Compared to other established techniques, such as oocyte freezing, ovarian tissue cryopreservation preserves actual organ function and thus the production of sex hormones. Endometriosis in perimenopausal women is rare, however it can be surprising diagnosis in the planned transplantation of cryopreserved ovarian tissue and the already thawed tissue may not be transplanted, so that it has to be refrozen., Results: Ovarian function returned in the patient two months after transplantation, as shown by estrogen production. Ten months after the ovarian tissue transplantation mild stimulation with FSH was initiated in accordance with a low-dose protocol. When ultrasonography revealed a follicle 17 mm in size in the ovarian graft, hCG was added and after follicular puncture one oocyte was obtained. The oocyte could be fertilized by IVF and transferred to the uterus. On day 14 after embryo-transfer, a positive hCG-Level was detected and after an uncomplicated pregnancy a healthy child was delivered., Conclusions: We report the first pregnancy and live birth achieved using transplantation of thawed and refrozen ovarian tissue in a woman treated by chemotherapy and subsequent endometriosis surgery. Refreezing of cryopreserved ovarian tissue is not a hindrance to successful transplantation of ovarian tissue. Against the background of increasing numbers of candidates for transplantation of ovarian tissue is expected that the combination chemotherapy followed by endometriosis will increase., (© 2022. The Author(s).)

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all the authors are listed in the long German-language version of the guideline report./Die Interessenkonflikte der Autoren sind im Leitlinienreport aufgelistet., (Thieme. All rights reserved.)

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all the authors are listed in the long German-language version of the guideline report./Die Interessenkonflikte der Autoren sind im Leitlinienreport aufgelistet., (Thieme. All rights reserved.)

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

Background: The impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident., Primary Objective: Evaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence., Study Hypothesis: Comprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65., Trial Design: Open label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended., Major Inclusion Criteria: Patients with histologically confirmed endometrial cancer stages pT1b-pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible., Exclusion Criteria: Patients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease., Primary Endpoint: Overall survival calculated from the date of randomization until death., Sample Size: 640 patients will be enrolled in the study., Estimated Dates for Completing Accrual and Presenting Results: At present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031., Trial Registration: NCT03438474., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Uterine sarcomas represent a heterogeneous group of rare malignancies, derived from the myometrium, the endometrial stroma, and very rarely from the nonspecialized uterine soft tissue. The actual incidence is about 1.5 for Caucasian and 3.0 for Afro-American women. There is no grading system for leimoysarcoma defined by the WHO classification; however, if clinicians request, the FNCLCC grading can be specified in analogy to soft tissue sarcomas. Adenosarcomas must be distinguished from adenofibromas (the existence of which is questionable)-with the vast majority of these tumors being uterine adenosarcomas. Within adenosarcomas, deep myometrial invasion (>50%), sarcomatous overgrowth, and a high-grade heterologous component are associated with a higher recurrence rate and poor survival. The immunohistochemical panel represents a very helpful tool for distinguishing low-grade from high grade endometrial stromal sarcomas (ESS) and may be supplemented by molecular analyses. Steroid hormone receptor analysis should be performed for all ESS due to the possible therapeutic relevance. Undifferentiated uterine sarcomas represent a diagnosis of exclusion and have a very poor prognosis. Carcinosarcomas represent a special subtype of endometrial carcinomas and are in fact not uterine sarcomas. Uterine sarcomas may present substantial intratumoral heterogeneity and adequate embedding is mandatory. Lesions ≤2 cm in the largest dimension should be processed completely and larger tumors should be processed with one block per centimeter for the largest tumor dimension.

Aims This is an official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of how they should be managed clinically, and treatment requires a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is the result of the consensus of a representative interdisciplinary group of experts who carried out a systematic search of the literature on uterine sarcomas in the context of the guidelines program of the DGGG, OEGGG and SGGG. Members of the participating professional societies achieved a formal consensus after a moderated structured consensus process. Recommendations The consensus-based recommendations and statements include the epidemiology, classification, staging, symptoms, general diagnostic work-up and general pathology of uterine sarcomas as well as the genetic predisposition to develop uterine sarcomas. Also included are statements on the management of leiomyosarcomas, (low and high-grade) endometrial stromal sarcomas and undifferentiated uterine sarcomas and adenosarcomas. Finally, the guideline considers the follow-up and morcellation of uterine sarcomas and the information provided to patients., (© Thieme Medical Publishers.)

Objective: To compare operating time and blood loss in patients undergoing total laparoscopic hysterectomies (TLH) for benign conditions with either the Marseal™ IQ 5 mm (MS) or the Ligasure™ 5 mm (LS) vessel-sealing device., Design and Setting: A randomized controlled clinical trial (RCT) in two German gynecology departments., Patients: 74 patients scheduled to undergo TLH for a symptomatic fibroid uterus, adenomyosis or severe meno-metrorrhagia., Interventions: Patients were randomized to receive a TLH with either the MS or the LS device. 27 variables were prospectively collected to address potential confounding issues., Measurement and Main Results: Operating time, defined as the time period between the first (round ligament dissection) and the last (uterine vessels sealing) use of the device, estimated and calculated intraoperative blood loss. The mean operating time (95% confidence interval, CI) was 22.7 min (95% CI 17.6-27.7) for LS and 26.4 min (95% CI 20-32.8) for the MS device (p = .89). The estimated intraoperative blood loss was 164 ml (95% CI 110-217) for LS and 160 ml (95% CI 116-203) for the MS device (p = .36). The multivariate analyses accounting for BMI, endometriosis, uterine weight and appearance of fibroids did not reveal any significant effect of the type of device used on operating time and estimated blood loss., Conclusion: In this RCT, both devices provided reliable and effective sealing and dissection. The reusable MS showed non-inferiority against the disposable LS device with regard to operating time and estimated intraoperative blood loss.

Uterine carcinosarcomas are rare tumors that account for less than 5% of all uterine malignancies. These tumors (previously called malignant mixed Müllerian tumors) are dedifferentiated carcinomas that comprise carcinomatous and sarcomatous elements and arise from a single malignant clone. They are considered a high-risk variant of endometrial adenocarcinoma because carcinosarcomas share more similarities in epidemiology, risk factors, and clinical behavior with endometrial carcinoma than with uterine sarcomas. The clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma will be discussed in this review., (© 2018 S. Karger GmbH, Freiburg.)

Uterine adenosarcoma is a rare malignancy. It is defined as a biphasic tumor composed of both sarcomatous stroma and benign epithelium. While the sarcomatous component usually is a low-grade homologous uterine sarcoma, the epithelium most often consists of endometrium-like cells. If the sarcomatous part occupies more than 25% of the tumor volume, the situation is referred to as sarcomatous overgrowth - accounting for about 10% of cases. While adenosarcoma usually may be considered a tumor of low malignant potential, the sarcomatous overgrowth most often presents as high-grade sarcoma and is associated with aggressive clinical behavior. Adenosarcomas stage I without sarcomatous overgrowth have a rather good prognosis, with a 5-year overall survival up to 80%. For treatment, complete surgical removal is advocated. Adjuvant chemotherapy and radiotherapy are not defined. Recurrences should again be treated surgically, attempting to achieve complete tumor resection. While the optimum medical treatment for relapsed and metastasized adenosarcomas has yet to be found, chemotherapy and endocrine therapy are potential options., (© 2018 S. Karger GmbH, Freiburg.)