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Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1 /2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non- BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer. • This publication provides European consensus recommendations from a multidisciplinary panel of experts from across Europe. • PRISMA guidelines and a systematic review of the literature were used to guide and support the consensus statements. • The statements provide guidance on BRCA and HRR deficiency testing for recently diagnosed patients with ovarian cancer. • The statements also provide considerations on how testing should be carried out in the clinic. • We believe that consensus documents are an effective means of focussing the opinions of a wide group of experts. [ABSTRACT FROM AUTHOR]

Abstract: Quality of surgery is one of the most important determinants of the outcome in ovarian cancer patients. Surgery by a gynaecological oncologist in a specialised, high-volume environment and removal of all visible tumours are associated with a higher likelihood of favourable outcome for patients with advanced-stage ovarian cancer. Population-based studies in Europe however show that a substantial number of patients do not receive optimal surgical care. Less than half of the patients suffering from advanced-stage ovarian cancer are operated by a gynaecological oncologists. Also the proportion of patients operated in a high-volume or specialised hospital is lower than 50%. In a substantial number of patients, minimum standard procedures are not performed and optimal tumor debulking is not achieved. To improve the quality of care, efforts are needed to develop and implement robust evidence-based European guidelines, provide surgical training for gynaecological oncologists and establish comprehensive cancer networks with sufficient resources. [ABSTRACT FROM AUTHOR]

Background Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients. Methods The cohort included 257 primary HGSOC patients treated by cytoreduction and platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples. BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction (PCR). Results 14.8% of patients presented hypermethylation within a selected region of the BRCA1 promoter. The rate of hypermethylation was significantly higher in younger patients (20.8% hypermethylation in the age group > 58years versus 8.7% hypermethylation in the age group >58years; p=0.008). Optimal tumour debulking could be reached in 63% of patients, without significant differences in the extent of residual disease with respect to the methylation status. No impact of BRCA1 gene promoter methylation status on progression free- and overall-survival rates was found. No significant differences within BRCA1 promoter methylation status between primary and metastatic tissue could be observed. These results on BRCA1 promoter methylation status were also confirmed in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations. Conclusions Our data suggest that BRCA1 methylation determines the earlier onset of HGSOC. Furthermore our study supports the idea that BRCAness is not only due to mutations but also to epigenetic changes in BRCA1 promoter gene. [ABSTRACT FROM AUTHOR]

Background: Quality of surgical care as a crucial component of a comprehensive multi-disciplinary management improves outcomes in patients with endometrial carcinoma, notably helping to avoid suboptimal surgical treatment. Quality indicators (QIs) enable healthcare professionals to measure their clinical management with regard to ideal standards of care., Objective: In order to complete its set of QIs for the surgical management of gynecological cancers, the European Society of Gynaecological Oncology (ESGO) initiated the development of QIs for the surgical treatment of endometrial carcinoma., Methods: QIs were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for the identification of potential QIs and documentation of the scientific evidence, two consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians and patient representatives. QIs were defined using a structured format comprising metrics specifications, and targets. A scoring system was then developed to ensure applicability and feasibility of a future ESGO accreditation process based on these QIs for endometrial carcinoma surgery and support any institutional or governmental quality assurance programs., Results: Twenty-nine structural, process and outcome indicators were defined. QIs 1-5 are general indicators related to center case load, training, experience of the surgeon, structured multi-disciplinarity of the team and active participation in clinical research. QIs 6 and 7 are related to the adequate pre-operative investigations. QIs 8-22 are related to peri-operative standards of care. QI 23 is related to molecular markers for endometrial carcinoma diagnosis and as determinants for treatment decisions. QI 24 addresses the compliance of management of patients after primary surgical treatment with the standards of care. QIs 25-29 highlight the need for a systematic assessment of surgical morbidity and oncologic outcome as well as standardized and comprehensive documentation of surgical and pathological elements. Each QI was associated with a score. An assessment form including a scoring system was built as basis for ESGO accreditation of centers for endometrial cancer surgery., Competing Interests: Competing interests: NC: advisory boards for Akesobio, Ensai, GSK, AstraZeneca, Mersana, Seattle Genetics, eTherRNA immunotherapies; NV grants for travelling from Roche, Genmab, Amgen and educational fees from MSD, Medscape Oncology, TouchIME. NRA-R: research grants (paid to his institution) from Stryker/Novadaq and GRAIL and funds from the NIH/NCI Cancer Center (support grant P30 CA008748). BA: advisory boards for Roche, Tesaro/GSK, Amgen, MSD; grants for traveling from Roche, Tesaro/GSK, Pharmamar; and educational fees from Roche, Tesaro/GSK, Celgene, Clovis, AstraZeneca, Novartis. DC: advisory boards for Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, Sotio. AF: advisory boards for AstraZeneca, MSD and grants for traveling from Pharmamar. CF: advisory boards for Roche, Ethicon, Sequana, GSK, MSD/AZ, Clovis, Tesaro. CM: advisory boards for Roche, Novartis, Amgen, MSD, AstraZeneca, Pfizer, Pharmamar, Cerulean, Vertex, Tesaro, GSK and grants for traveling from Roche, Novartis, Amgen, MSD, Pharmamar, AstraZeneca, Tesaro, GSK. DQ: advisory boards for Arquer Diagnostics Ltd. JS: advisory boards for Novocure, Roche, Pfizer, AstraZeneca, GSK, Clovis, Eisei and grants for traveling from Roche, GSK, AstraZeneca. IV: consulting activities for Agenus, Aksebio, Amgen (Europe) GmbH, AstraZeneca, Bristol Myers Squibb, Clovis Oncology Inc, Carrick Therapeutics, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffman-La Roche Ltd, Genmab, GSK, Immunogen Inc, Jazzpharma, Karyopharm, Mersana, Millenium Pharmaceuticals, MSD, Novocure, Novartis, Octimet Oncology, NV, Oncoinvent AS, Seagen, Sotio a.s., Verastem Oncology, Zentalis; contracted research (via KULeuven) for Oncoinvent AS, Genmab; corporate sponsored research for Amgen, Roche; and grants for traveling and accommodations from Amgen, MSD, Tesaro, AstraZeneca, Roche. PW: advisory boards for Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, Clovis, GSK and grants for traveling from Roche, Novartis, AstraZeneca. JP: advisory boards for Intuitive surgical, Medtronics., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement., Competing Interests: Competing interests: DT: senior investigator FWO (Fund for Scientific Research Flanders), and research sponsored by Roche Diagnostics. KU Leuven has consultancy agreements with GE Healthcare, Samsung Healthcare, GSK, and Canon. TB: research sponsored by Roche Diagnostics, Samsung Medison and Illumina, and grants for traveling from Samsung Medison. LC: advisory boards for AstraZeneca, GSK, Takeda, and Roche. DC: advisory boards for Genmab, AstraZeneca, Roche, and Sotio. NC: advisory boards for AstraZeneca, Seattle Genetics, Mersana and eTheRNA Immunotherapies NV, grants for traveling from Roche, Genmab and Amgen, and educational fees from MSD and Medscape Oncology. AdB: advisory boards for Roche, AstraZeneca, GSK/Tesaro, BIOCAD, Clovis, Genmab/Seattle Genetics, Pfizer, and Amgen, and grants for traveling from Roche and AstraZeneca. IV: consulting activities for Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Debiopharm International SA, Deciphera Pharmaceuticals, Elevar Therapeutics, F Hoffmann-La Roche Ltd, Genmab, GSK, Immunogen Inc, Medical University of Vienna, Mersana, Millenium Pharmaceuticals, MSD, Novocure, Octimet Oncology NV, Oncoinvent AS, Pharmamar, Sotioa.s, Tesaro Inc, Verastem Oncology, and Zentalis, contracted research (via KU Leuven) from Oncoinvent AS and Genmab, grants (corporate sponsored research) from Amgen and Roche, and accommodations/travel expenses from Amgen, MSD, Tesaro, AstraZeneca, and Roche. CF: advisory boards for Roche, GSK, Tesaro, AZ/MSD, Clovis, Sequana and Ethicon, and grants for traveling from GSK and Roche. FP, CL, DF, WF, GG, BL, AL, LM, PM, DQ, ACT, VV and GS: no conflicts of interest., (© IGCS and ESGO 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Introduction: Long-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more personalized therapeutic approach. The objective of this study is to determine further characteristics of long-term survivors with high-grade serous ovarian cancer., Methods: Long-term survivors were defined as patients living longer than 8 years after first diagnosis and were recruited within seven high volume centers across Europe from November 1988 to November 2008. The control group included patients with high-grade serous ovarian cancer with less than 5 years' survival identified from the systematic 'Tumorbank ovarian cancer' database. A subanalysis of Charité patients only was performed separately for in-depth analysis of tumor dissemination. Propensity score matching with nearest-neighbor caliper width was used to match long-term survivors and the control group regarding age, FIGO stage, and residual tumor., Results: A total of 276 patients with high-grade serous ovarian cancer were included, divided into 131 long-term survivors and 145 control group patients. After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favorable prognostic factor whereas recurrence (p<0.001) and ascites (p=0.021) were independent detrimental predictors for long-term survival. Significantly more long-term survivors tested positive for mutation in the BRCA1 gene than the BRCA2 gene (p=0.016). Intraoperatively, these patients had less tumor involvement of the upper abdomen at initial surgery (p=0.024). Complexity of surgery and surgical techniques were similar in both cohorts., Conclusion: Platinum sensitivity constitutes a favorable factor for long-term survival whereas tumor involvement of the upper abdomen, ascites, and recurrence have a negative impact. Based on clinical estimation, long-term survival is associated with combinations of clinical, surgical, and molecular factors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined., (Copyright © 2021 International Gynecologic Cancer Society and European Society of Gynecological Oncology [Published by BMJ]; Springer Verlag GmbH Berlin Heidelberg, part of Springer Nature. Published by Elsevier B.V. All rights reserved.)

Background: Maintenance therapy induces remission and prolongs disease free interval in primary and recurrent ovarian disease. For the treatment decision making process, aspects of quality of life and patients' preferences are crucial, despite the fact that scientific data are lacking. Therefore, we conducted this European-wide study in patients with ovarian cancer., Methods: A 25 item questionnaire was provided to ovarian cancer patients via the internet or as a paper version in 10 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland, Turkey, and Spain). Data recorded were demographics, tumor stage, therapy after firstline and recurrent disease, preferences for administration, and expectations concerning maintenance therapy., Results: Overall, 1954 patients participated from September 2013 to March 2016; 42% had recurrent disease. Most patients (98%) with primary epithelial ovarian cancer underwent surgery followed by chemotherapy (91%). Almost one-third of participants (29%) were receiving maintenance therapy whereas 45% had only heard of it. For 70% of patients with primary epithelial ovarian cancer, they heard about maintenance therapy from their doctor, 10% heard about maintenance therapy from other patients, and 8% from the internet. The main source of information about maintenance therapy in patients with epithelial ovarian cancer relapse was from the treating physician (72%), from other patients (8%), and from the internet (7%). For patients undergoing maintenance therapy, the four most disturbing adverse effects were polyneuropathy (37%), nausea (36%), hair loss (34%), and vomiting (34%). The main objective of maintenance treatment, as perceived by patients, was to increase the chances of cure (73%), improvement in quality of life (47%), and delay in tumor growth (37%). Many patients were willing to undergo maintenance therapy until tumor progression (38%) and 39% would prefer oral administration. No significant differences were detected in the cross country subanalysis regarding expectations of maintenance therapy and patients with primary or relapsed ovarian cancer., Conclusion: Patients with ovarian cancer were willing to accept maintenance therapy of prolonged duration and preferred oral administration. There is still a gap between the efficacy of maintenance therapy and patient expectations. Patients need more information on the adverse effects and treatment goals of maintenance therapy to avoid misunderstandings., Competing Interests: Competing interests: FJ is on the advisory board and symposium of Astra Zeneca, Roche, Tesaro, Ipsen Pharma GmbH, Janssen, Pfizer, Bristol-Myers Squibb and MSD, outside the submitted work. RB reports personal fees from Roche and from AstraZeneca, outside the submitted work. AdB reports personal fees from Astra Zeneca, Roche, BioCard, Tesaro, Pfizer, Clovis, Genmab, and MSD, outside the submitted work. IV reports consulting or advisory role (institution) for Advaxis Inc, Eisai Inc, MSD Belgium, Roche NV, Genmab A/S, Genmab US, F Hoffmann-La Roche Ltd, Pharmamar, Millennium Pharmaceuticals, Clovis Oncology Inc, AstraZeneca NV, Tesaro Bio GmbH, Tesaro Inc, Oncoinvent AS, Immunen Inc; research funding (via KU Leuven) from Oncoinvent AS, Genmab A/S-Genmab BV; corporate sponsored research grants from Amgen, Roche, and Stichting teen Kanker; travel, accommodation, and expenses from Takeda Oncology, Pharmamar, Genmab, Roche, AstraZeneca, and Tesaro, outside the submitted work. DL reports grants and personal fees from Tesaro, personal fees from Astra Zeneca, grants and personal fees from Merck, grants and personal fees from Clovis, and personal fees from Merrimack, outside the submitted work. JM reports personal fees and non-financial support from Roche, and personal fees from Tesaro, AstraZeneca, and Clovis, outside the submitted work. JS reports honoraria from Astra Zeneca, Eisai, Clovis, Olympus, Johnson&Johnson, PharmaMar, Pfizer, TEVA, TESARO, and MSD; consulting or advisory role for Astra Zeneca, Clovis, Lilly, PharmaMar, Pfizer, Roche, TESARO, and MSD; research funding from Astra Zeneca, Clovis, Merck, Bayer, PharmaMar, Pfizer, TESARO, and MSD; travel, accommodation, and expenses from Astra Zeneca, Clovis, PharmaMar, Roche, Pfizer, TESARO, and MSD, outside the submitted work., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of the Review: More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of <6 per 100,000) and such tumours represent an important challenge for clinicians., Recent Findings: Rare cancers account for more than one fifth of all new cancer diagnoses, more than any of the single common cancers alone. Reviewing the RARECAREnet database, some of the tumours occur infrequently, whilst others because of their natural history have a high prevalence, and therefore appear to be more common, although their incidence is also rare. Harmonization of medical practice, guidelines and novel trials are needed to identify rare tumours and facilitate the development of new treatments. Ovarian tumours are the focus of this review, but we comment on other rare gynaecological tumours, as the diagnosis and treatment challenges faced are similar., Future: This requires European collaboration, international partnerships, harmonization of treatment and collaboration to overcome the regulatory barriers to conduct international trials. Whilst randomized trials can be done in many tumour types, there are some for which conducting even single arm studies may be challenging. For these tumours alternative study designs, robust collection of data through national registries and audits could lead to improvements in the treatment of rare tumours. In addition, concentring the care of patients with rare tumours into a limited number of centres will help to build expertise, facilitate trials and improve outcomes., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Backround: The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician-patient relationship and treatment., Patients and Methods: A questionnaire was developed based on the experiences of the national German survey 'Expression II', and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version., Results: From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17-89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: 'the therapy should not induce alopecia' (42%), 'there must be more done to counter fatigue' (34.5%) and 'the therapy should be more effective' (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included., Conclusion: This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing. Based on this review of newly updated guidance and up-to-date evidence, the following is recommended: all patients with invasive epithelial OC (excluding borderline or mucinous), including those with fallopian tube and peritoneal cancers, should be considered as candidates for referral for BRCA genetic testing, irrespective of age; genetic testing should ideally be offered at diagnosis, although patients can be referred at any stage; retrospective testing should be offered to patients in long-term follow-up because of the implications for family members and individual future breast cancer risk; and germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumour tissue should be tested (to identify non-germline [somatic] BRCA PARPi therapy candidates)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The European Network for Gynaecological Oncological Trial groups (ENGOT) is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Earlier, we reported on the ENGOT minimal requirements for trials between academic groups and pharmaceutical companies. In this paper, we summarize the roadmap for performing trials in the ENGOT framework. In this roadmap, we define how an ENGOT trial should be set up and discuss the following items: What are the conditions to classify a study as an ENGOT trial? What is an ENGOT protocol? How are an ENGOT protocol, informed consent (ICF), and case report form (CRF) produced? How is the center selection and feasibility performed in ENGOT trials? How are regulatory and operational tasks handled? How should a confidentiality agreement between the industry and the whole ENGOT network be negotiated? How are contracts made between the industry and ENGOT and between ENGOT groups? How are funding, insurance, and communication flow arranged in ENGOT trials? What are the requirements for conducting substudies and what are the tasks for the leading group in an ENGOT trial? A template of a confidentiality agreement, a checklist of ENGOT criteria for new study proposals, and guidelines for authorship are also provided.

Introduction: The Sixth Framework Program European Union project OVCAD, "Ovarian Cancer-Diagnosis of a Silent Killer," aimed to investigate new predictors for early detection of minimal residual disease in epithelial ovarian cancer (EOC). Here we present the main pathologic, surgical, and chemotherapy characteristics of the OVCAD patient cohort., Methods: Between February 2005 and December 2008, 5 European gynecologic cancer centers (WP2 group) enrolled prospective 275 consecutive patients with EOC into this translational study. Inclusion criteria were as follows: advanced International Federation of Obstetrics and Gynecology II to IV stage, cytoreductive surgery, platinum-based chemotherapy, and collected tumor samples. WP2 coordinated the implementation, screening, and recruiting of the patients and tumor samples into a Web-based data bank according established standard operating procedures., Results: Median age at the time of diagnosis was 58 years. Most patients presented advanced high-grade EOC: International Federation of Obstetrics and Gynecology III/IV (94.5%), grade 2/3 (96%), serous histology (86.2%), ascites (76%), peritoneal carcinomatosis (67.6%), and lymph node involvement (52%). The most common surgical procedures were omentectomy (92.4%), bilateral salpingo-oophorectomy (90.9%), hysterectomy (77.3%), pelvic (69.5%) and paraaortic (66.9%) lymphadenectomy, and large (37.7%) or small bowel resection (13.4%). Patients were treated commonly with platinum-based therapy (98.2%). The macroscopic cytoreduction rate was 68.4%. After a median follow-up of 37 months, 70 patients (25.5%) developed a platinum-resistant recurrence. Biological materials such as tumor and paraffin tissue, ascites, and blood samples were collected consecutively., Conclusions: The implementation of the OVCAD cohort demonstrated the feasibility and advantages of an open, prospective, and multicenter recruitment inside a translational research study. Essential was the predefinition of all inclusion criteria, standard operating procedures, and Web-based software, which enabled the prospective patient recruitment and tissue sampling, minimizing institutional bias and variability in the quality of the biological samples. The translational concept of the OVCAD study does not conflict with the state-of-the-art surgical and chemotherapy management and guaranteed an improved outcome of patients with EOC.

Objective: The aim of this study is to evaluate the current opinion of the members of the European Society of Gynecological Oncology (ESGO) on the use of neoadjuvant chemotherapy (NACT) in stage IIIC and IV ovarian cancer., Methods: A link to a 21-item questionnaire, with questions about the management of patients with stage IIIC and IV ovarian cancer, was sent 3 times to the ESGO members (N = 1177)., Results: Of the 469 (40%) responding members, 70.2% believe there is sufficient evidence to use NACT followed by interval debulking for the treatment of stage IIIC and IV ovarian cancer. On the basis of a multivariable logistic regression analysis, no relationships between the belief in evidence for NACT and practice type (P = 0.15) or level of experience (P = 0.41) were observed. Only 5.3% of respondents never use NACT, and 30% uses NACT in less than 10% of their patients. Optimal debulking, defined as "no macroscopic residual tumor," is reported in more than 60% of the patients by 20% of the respondents at primary debulking, and by 34.6% of the respondents when interval debulking is performed. Whether a patient can be optimally primarily debulked is impossible to determine preoperatively according to 51.1% of the respondents. Computed tomographic scan (79.4%) and clinical examination (72.5%) are regarded as the most important modalities to predict operability. Diagnostic laparoscopy is used by 46.3% of the respondents. The most important reasons for choosing NACT are bulky disease in the upper abdomen (64.7%) and stage IV disease (58.7%)., Conclusions: Of the responding ESGO members, 70% believe there is sufficient evidence to treat patients with stage IIIC-IV ovarian cancer with NACT, and 30% uses NACT in less than 10% of their patients.

Background: Early ovarian cancer patients are often incompletely staged during initial surgery.(1-3) This omission can have serious adverse consequences for the prognosis of patients as the completeness of surgical staging has been identified as an independent prognostic parameter for survival.(4,5) The reasons for the problem of inadequate staging of early ovarian cancer are largely unknown. We have analysed the data of a large randomised trial in early ovarian cancer in which detailed information of the surgical staging procedure was monitored.(5), Methods: Data of the EORTC Adjuvant ChemoTherapy In Ovarian Neoplasm (ACTION) Trial were used in which 448 early ovarian cancer patients were randomised between postoperative chemotherapy in one arm and observation following surgery in the other. In this trial strict criteria for surgical staging were advised but optimal, complete staging was performed in only 1/3 of patients. Staging characteristics of the incompletely staged patients were analysed and factors that could explain the failure to perform a complete staging were studied., Results: Sampling of para-aortic nodes was omitted in 78% of the incompletely staged patients, while 52% of these patients had no pelvic lymph node dissection. Taking blind biopsies from different peritoneal sites was not performed in more than 1/3 of the incompletely staged group. Omission of the staging steps ranged from 3% (infracolic omentectomy) to 55% (biopsy of the right hemi-diaphragm). A significant difference (p=0.04) between the fraction of completely staged patients was found when comparing institutes who entered less than 5 patients (21%) versus those who included more than 20 patients (37%) in the trial., Conclusions: Even in a randomised trial in which comprehensive surgical staging was strongly advised in the study protocol the majority of patients (66%) were incompletely staged. Factors relating to a lack of surgical skills attributed most to the number of incompletely staged patients, but insufficient knowledge of the tumour behaviour and routes of spread of ovarian cancer also contributed substantially to this problem. Multicentre trials recruiting patients from many institutes with small volume contribution to the study, run the risk of inadequate adherence to the study protocol., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The Piver classification of radical hysterectomy for the treatment of cervical cancer is outdated and misused. The Surgery Committee of the Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer (EORTC) produced, approved, and adopted a revised classification. It is hoped that at least within the EORTC participating centers, a standardization of procedures is achieved. The clinical indications of the new classification are discussed.

Uterine adenosarcoma (UAS) is microscopically characterized by a biphasic growth pattern. By definition, the epithelial component is benign, whereas the stromal component typically has the appearance of a low-grade sarcoma, usually an endometrial stromal sarcoma. CD10 acts by reducing cellular response to peptide hormones and is currently regarded as a specific marker for endometrial stromal tumors. In this international multicenter study, we further explored CD10 immunoreactivity in 30 UASs. We encountered CD10 positivity of the sarcomatous component in 18/20 (90%) of UASs, in five of eight (63%) of UASs with sarcomatous overgrowth as well as in both cases of recurrent UAS. The epithelial component stained negative in all cases. These findings suggest that CD10 can be used to differentiate UAS from cellular leiomyoma, or in case endometrial stromal cells exhibit muscle differentiation. Furthermore, CD10 positivity in recurrent UAS might guide the pathologist toward an endometrial stromal origin.

Quality control of medical performance requires adequate 'state-of-the-art' data and this is currently not uniformly defined for radical hysterectomy. We have used data from a randomised multicentre clinical trial examining the clinical significance of surgical drains following radical hysterectomy (European Organisation for Research and Treatment of Cancer (EORTC)-55962). Although the study was not designed to analyse the quality of the surgical procedure per se, surgical data during and after the operation were carefully noted. A total of 234 patients from 12 European institutes were included in the study. We reported on the clinical and surgical characteristics, the radicality of surgery and short- and long-term complications of radical hysterectomy: median duration of surgery: 240 min; median number of nodes removed: 26; lymph node metastases: 22%; post-operative mortality: <1%; urinary tract infection: 42%; deep venous thrombosis: 3%; fistula: 2%. The data from our study provides an honest and realistic picture of the current practice of radical hysterectomy among European oncology centres and may be considered as the 'standard of care' in this part of the world.

In 1962, the European Organisation for Research and Treatment of Cancer (EORTC) was founded, and in the course of the years it developed into the leading European organisation in cancer research. Currently, the EORTC is organised into (Pre-)Clinical Groups and Task Forces consisting of scientists and/or clinicians. One of these groups with a specific area of interest in cancer research is the Gynaecological Cancer Group (GCG). The EORTC offers fellowship programmes to physicians and scientists from all over the world to create a possibility to be temporarily linked to an EORTC group or a specific research project. Over the past decade, 76 research fellowships have been appointed at the EORTC Data Center. This paper shows an overview of the activities of one EORTC/GCG medical fellow., (Copyright 2004 S. Karger AG, Basel)

First-line intravenous chemotherapy (CT) following debulking surgery is associated with prolonged survival, in particular in patients who achieve a pathological complete remission (pCR) at second-look surgery but in whom a high rate of relapses still occurs. Between 1988 and 1997, 153 patients in pCR following platinum-based intravenous CT were randomized between four courses of intraperitoneal cisplatin (P) (90 mg/m2 every 3 weeks) or observation. Overall survival (OS) was the primary endpoint, while progression-free survival (PFS) was a secondary endpoint. This intent-to-treat analysis includes 16 patients who were not eligible and 17 patients who had protocol violations. The two groups were well balanced in terms of age (median = 55 years), performance status (78% P.S. O), FIGO stage (96% stage III), histology (serous in 66%), grade (2 or 3 in 80%), and residuum before intravenous CT (>1 cm in 40%). Intraperitoneal CT was delivered mainly through intraperitoneal catheters (Port-a-Cath 61% and Tenckhoff 25%). Side effects of intraperitoneal cisplatin included vomiting [> or =grade 2 (82%)], rise in serum creatinine [> or =grade 2 (14%)], abdominal pain [grade 1-2 (38%)], and neurotoxicity [grade 2-3 (15%)]. After a median follow-up of 8 years, 80 patients (52%) have progressed with no difference in the pattern of relapse between the two groups and 75 patients (49%) have died; the respective hazard ratios for PFS and OS with 95% CI are 0.89 (0.59-1.33) and 0.82 (0.52-1.29). These results are suggestive of a treatment benefit but do not support a change in clinical practice. Other randomized clinical trials of intraperitoneal CT are reviewed and briefly discussed.

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European-Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin-paclitaxel regimen over cisplatin-cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Background: All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging., Methods: Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan-Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were two-sided., Results: After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.44 to 1.08; P =.10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P =.02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 [95% CI = 1.08 to 4.96]; P =.03 and HR = 1.82 [95% CI = 1.02 to 3.24] P =.04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 [95% CI = 1.04 to 2.95]; P =.03 and HR = 1.78 [95% CI = 1.15 to 2.77]; P =.009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen., Conclusion: Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.

Objective: To investigate the clinical activity and toxicity of a combination chemotherapy consisting of cyclophosphamide (C), adriamycin (A) and cisplatin (P) for patients with primary adenocarcinoma of the Fallopian tube having FIGO stage III-IV disease., Methods: The CAP-regimen consisted of cyclophosphamide 600 mg/m2, adriamycin 45 mg/m2, and cisplatin 50 mg/m2 administered intravenously on day one every 28 days., Results: Twenty-four eligible patients with histologically-confirmed Fallopian tube adenocarcinoma were entered in the trial. Fourteen patients had FIGO stage III, and ten had stage IV disease. The median number of CAP cycles was six. Ten patients had a complete and six had a partial response (response rate: 67%, 95% confidence limits: 45-84%). WHO grade III-IV side-effects included haematological toxicity, nausea/vomiting and alopecia. Furthermore, mild signs of cisplatin-related peripheral neurotoxicity were observed. At a median follow-up of 40 months, nine patients were alive and 15 had died due to malignant disease. The median time to progression was 13 months for all patients. The median overall survival was 24 months and the 1-, 3- and 5-year survival and their 95% confidence limits were 73% (54-92%), 25% (4-46%) and 19% (0-38%), respectively., Conclusion: The present data confirm the therapeutic activity of the CAP-regimen in primary Fallopian tube adenocarcinoma. The response rate is moderate and the toxicity profile is acceptable.