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Ovarian cancer survival in the UK lags behind comparable countries. Results from the ongoing National Ovarian Cancer Audit feasibility pilot (OCAFP) show that approximately 1 in 4 women with advanced ovarian cancer (Stage 2, 3, 4 and unstaged cancer) do not receive any anticancer treatment and only 51% in England receive international standard of care treatment, i.e., the combination of surgery and chemotherapy. The audit has also demonstrated wide variation in the percentage of women receiving anticancer treatment for advanced ovarian cancer, be it surgery or chemotherapy across the 19 geographical regions for organisation of cancer delivery (Cancer Alliances). Receipt of treatment also correlates with survival: 5 year Cancer survival varies from 28.6% to 49.6% across England. Here, we take a systems wide approach encompassing both diagnostic pathways and cancer treatment, derived from the whole cohort of women with ovarian cancer to set out recommendations and quality performance indicators (QPI). A multidisciplinary panel established by the British Gynaecological Cancer Society carefully identified QPI against criteria: metrics selected were those easily evaluable nationally using routinely available data and where there was a clear evidence base to support interventions. These QPI will be valuable to other taxpayer funded systems with national data collection mechanisms and are to our knowledge the only population level data derived standards in ovarian cancer. We also identify interventions for Best practice and Research recommendations.

Introduction/Background* Same-day discharge (SDD) has been found to be safe and attainable following minimally invasive surgery (MIS) for gynaecological cancer.1 We audited the compliance to SDD, opposed to 24 hours discharge, at the Royal London Hospital. Methodology We performed a retrospective audit of all minimally invasive hysterectomies performed at the Royal London Hospital in 2019 and 2020. All patients were identified for SDD at pre-op clinic and were followed up until 30 days post discharge. Data was collected from electronic patient to record demographic, operating time & outcome, postoperative recovery (+/- complication and readmission) and time of discharge. Following the first audit cycle in 2019, interventions were performed comprising of staff education to highlight the human factors that led to failed SDD (including delayed prescriptions, discharge summaries and removal of catheters). Result(s)* A total of 12 patients were selected for SDD in 2020 compared to 22 in 2019 with 30 day follow up for all patients. Numbers of patient in 2020 was reduced due to covid. Successful SDD was achieved in 42% of cases in 2020 compared to 56% in 2019. Of those planned for SDD, 50% of those that failed were due to unavoidable intraoperative complications. No SDD discharges in 2020 failed due to pharmacy, transport or discharge documentation delays (7 failed SDD in 2019 due to these factors). No re-admissions or complications were recorded. Conclusion* Same day discharge continues to be safe and achievable following minimally invasive surgery for gynecological cancer, despite disruption from the Covid-19 pandemic. Auditing and implementation of interventions helps improve this pathway. Reference Korsholm M, Mogensen O, Jeppesen MM, Lysdal VK, Traen K, Jensen PT. Systematic review of same-day discharge after minimally invasive hysterectomy. Int J Gynaecol Obstet 2017 Feb;136(2):128–137. doi: 10.1002/ijgo.12023. Epub 2016 Nov 11. PMID: 28099736.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed &gt, 1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p &lt, 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Key content Cervical cancer continues to affect many women in the UK with over half under the age of 45 years at the time of diagnosis; with a trend towards starting families later in life this raises fertility concerns. While the standard treatment for stage IA2 or IB1 cervical cancer is a radical hysterectomy, radical trachelectomy has been shown to have equivalent 5-year survival and is a surgical option if there is a wish to preserve fertility. Although trachelectomies are performed by gynaecological oncologists, the management of any subsequent pregnancies falls under the remit of obstetricians who therefore require a sound knowledge of the procedure and potential obstetric sequelae. Pregnancies following trachelectomy are high risk because of the increased rate of mid-trimester miscarriage and preterm delivery, often as a consequence of preterm prelabour rupture of membranes. Delivery is by caesarean section, traditionally by classical section as a permanent isthmic suture is placed at the time of trachelectomy, but nowadays a transverse incision may be used to reduce morbidity and the implications on future fertility. Learning objectives Management of a pregnancy following radical trachelectomy. Intrapartum care of post-radical trachelectomy pregnancy and complication risks. Impact of trachelectomy and subsequent pregnancy on the woman. Ethical issues Informed consent surrounding trachelectomy and future pregnancies.

Introduction/Background Obesity increases endometrial cancer risk; 1.6-fold with every 5 kg/m2 increase in BMI. High BMI is associated with additional surgical and anaesthetic risks and prolonged operating time. Robotic surgery is a promising route in obese women. Short-term data show no statistically significant difference in survival rates between robotic and abdominal (Hinshaw et al. 2016) and laparoscopic surgery for endometrial cancer (Corrado et al. 2018). The aims were to review whether the introduction of robotic surgery has increased minimally invasive surgery (MIS) rate in obese women and to assess the effect of BMI on console time. Methodology Data was prospectively collected for all women undergoing surgery for endometrial cancer in a London tertiary unit in 2016 and 2018 (robotic surgery was introduced in 2017) and analysed using Microsoft Excel. Results In 2016, 95 women had surgery. Following examination under anaesthetic, 53 (56%) had total abdominal hysterectomy (TAH) and 42 (44%) total laparoscopic hysterectomy (TLH). In 2018, 103 underwent surgery; 37 (35%) TAH and 66 (65%) MIS, of which 21 (31%) had TLH and 45 (69%) robotic hysterectomy (RAH). The mean BMI for MIS in 2018 was 36.2 kg/m2 vs 32.2 kg/m2 in 2016 (p=0.023). BMI range was 16–53 kg/m2 in 2016 and 25–62 kg/m2 in 2018. For BMI >30 kg/m2, 21/42 (50%) had MIS in 2016 vs 42/66 (64%) in 2018 (p=0.02). In 2016, the median length of stay (LOS) was 5 days for BMI >30 undergoing MIS vs 1 day in 2018 (p=0.04). BMI had no impact on console time (p=0.064). Conclusion The introduction of robotic surgery has significantly increased the MIS rate and reduced LOS for obese women with endometrial cancer; with no increase in operative time as BMI rises. Disclosure Nothing to disclose.

Purpose: The purpose of this study was to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSC), and its relationship to treatment response. Experimental Design: We obtained pre- and posttreatment omental biopsies and blood samples from a total of 54 patients undergoing platinum-based NACT and 6 patients undergoing primary debulking surgery. We measured T-cell density and phenotype, immune activation, and markers of cancer-related inflammation using IHC, flow cytometry, electrochemiluminescence assays, and RNA sequencing and related our findings to the histopathologic treatment response. Results: There was evidence of T-cell activation in omental biopsies after NACT: CD4+ T cells showed enhanced IFNγ production and antitumor Th1 gene signatures were increased. T-cell activation was more pronounced with good response to NACT. The CD8+ T-cell and CD45RO+ memory cell density in the tumor microenvironment was unchanged after NACT but biopsies showing a good therapeutic response had significantly fewer FoxP3+ T regulatory (Treg) cells. This finding was supported by a reduction in a Treg cell gene signature in post- versus pre-NACT samples that was more pronounced in good responders. Plasma levels of proinflammatory cytokines decreased in all patients after NACT. However, a high proportion of T cells in biopsies expressed immune checkpoint molecules PD-1 and CTLA4, and PD-L1 levels were significantly increased after NACT. Conclusions: NACT may enhance host immune response but this effect is tempered by high/increased levels of PD-1, CTLA4, and PD-L1. Sequential chemoimmunotherapy may improve disease control in advanced HGSC. Clin Cancer Res; 22(12); 3025–36. ©2016 AACR.

Background: The chemotherapy response score (CRS) has been recommended for reporting histological tumour response to neoadjuvant chemotherapy (NACT) in tubo-ovarian high-grade serous carcinoma (HGSC). The CRS reproducibly stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response. Studies have shown an association between CRS and progression-free survival (PFS) but not overall survival (OS). Methods: We undertook a systematic review and meta-analysis and established an international collaboration to pool individual patient data (IPD) from 16 sites in 11 countries. All patients had stage IIIC/IV HGSC, received 3-4 NACT cycles and a minimum 6-month follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and PFS and OS. Findings: 5 studies were identified that included 490 patients: 4 were at low-risk of bias. Unpublished IPD for 875 patients were obtained. 907 patients were included. Median PFS was 15 months (IQR 6-66) and median OS was 28 months (IQR 7-90). The pooled hazard ratio (HR) for PFS (CRS3 compared to CRS1/CRS2) was 0·52 (95%CI, 0·43 - 0·63; P

Tumours with profound copy-number aberration elude molecular stratification due to their genomic complexity. By representing this complexity as a mixture of copy-number signatures, we provide molecular explanations for differing clinical outcomes. Here we present a method for copy-number signature identification, deriving eight signatures in 117 shallow whole-genome sequenced high-grade serous ovarian cancers (HGSOC), which validated on independent cohorts of 95 deep whole-genome sequenced, and 402 SNP array-profiled cases. Three copy-number signatures predicted longer overall survival, while the others predicted poorer outcome. We found evidence for the mutational processes giving rise to copy-number change for six of the eight signatures via correlations with other genomic features. Our results provide insights into the pathogenesis of HGSOC by uncovering multiple mutational processes that shape genomes following TP53 mutation. Importantly, our work shows that most HGSOC have a mixture of mutational processes suggesting that targeting a single mutator phenotype may be therapeutically suboptimal.

BACKGROUND: The genomic complexity of profound copy-number aberration has prevented effective molecular stratification of high grade serous ovarian carcinoma (HGSOC). Recent algorithmic advances have enabled interpretation of complex genomic changes by identifying mutational signatures—genomic patterns that are the imprint of mutagenic processes accumulated over the lifetime of a cancer cell. We hypothesized that specific features of copy-number (CN) abnormalities could represent the imprints of distinct mutational processes, and developed methods to identify signatures from copy-number features in HGSOC. METHODS: We derived copy-number signatures from absolute copy number profiles from 253 primary and relapsed HGSOC samples from 132 patients in the BriTROC-1 cohort using low-cost shallow whole-genome sequencing (sWGS; 0.1×). A subset of 56 of these cases had deep whole-genome sequencing (dWGS) performed for mutation analysis and comparison with sWGS data. Independent validation was performed using 112 dWGS HGSOC cases from PCAWG and 415 HGSOC cases with SNP array and whole exome sequence from TCGA. CN signature exposures were correlated with mutation data, SNV signatures, and other measures derived from deep WGS and exome sequencing to identify statistically significant genomic associations using a false discovery rate RESULTS: We identified 7 CN signatures that provided a molecular framework to rederive the major defining elements of HGSOC genomes, including defective homologous recombination (HRD), tandem duplication, amplification of CCNE1 and amplification-associated fold-back inversions. Almost all patients with HGSOC demonstrated a mixture of signatures indicative of combinations of mutational processes, including those with early driver events such as BRCA2 mutation (in addition to HRD signatures). High exposure to CN signature 3, characterised by BRCA1/2-related HRD, was associated with improved overall survival. Conversely, high exposure to signature 1, which was characterised by oncogenic RAS signaling (including NF1, KRAS and NRAS mutation), predicted platinum-resistant relapse and poor survival. CONCLUSIONS: HGSOC lacks clinically-relevant patient stratification, which is reflected in poor survival and is a significant barrier to precision medicine. Copy-number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Our results suggest that early TP53 mutation, the ubiquitous initiating event in HGSOC, may permit multiple mutational processes to co-evolve, potentially simultaneously and that additional signature exposures may alter the risk of developing therapeutic resistance. Thus, our results suggest that HGSOC is a continuum of genomes. We derived signatures using inexpensive sWGS of DNA from core biopsies. These approaches are rapid and cost effective, thus providing a clear path to clinical implementation. By dissecting the mutational forces shaping HGSOC genomes, our study paves the way to understanding extreme genomic complexity, as well as revealing the evolution of tumors as they relapse and acquire resistance to therapy. Citation Format: Geoff Macintyre, Teodora E. Goranova, Dilrini De Silva, Darren Ennis, Anna M. Piskorz, Matthew Eldridge, Daoud Sie, Liz-Anne Lewsley, Aishah Hanif, Cheryl Wilson, Suzanne Dowson, Rosalind M. Glasspool, Michelle Lockley, Elly Brockbank, Ana Montes, Axel Walther, Sudha Sundar, Richard Edmondson, Geoff D. Hall, Andrew Clamp, Charlie Gourley, Marcia Hall, Christina Fotopoulou, Hani Gabra, James Paul, Anna Supernat, David Millan, Aoisha Hoyle, Gareth Bryson, Craig Nourse, Laura Mincarelli, Luis Navarro Sanchez, Bauke Ylstra, Mercedes Jimenez-Linan, Luiza Moore, Oliver Hofmann, Florian Markowetz, Iain A. McNeish, James D. Brenton. COPY-NUMBER SIGNATURES AND MUTATIONAL PROCESSES IN HIGH GRADE SEROUS OVARIAN CARCINOMA [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP09.

Risk-reducing-salpingectomy and Delayed-Oophorectomy (RRSDO) is being proposed as a two-staged approach in place of RRSO to reduce the risks associated with premature menopause in high-risk women. We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO. Baseline characteristics were described using descriptive statistics. A Chi square test was used to compare categorical, Kendal-tau-b test for ordinal and Mann–Whitney test for continuous variables between two groups. 173/708 (24.4 %) of invitees responded. 71 % respondents (CGG = 57 %/BGCS = 83 %, p = 0.005) agreed with the tubal hypothesis for OC, 55 % (CGG = 42 %/BGCS = 66 %, p = 0.003) had heard of RRSDO and 48 % (CGG = 46 %/BGCS = 50 %) felt evidence was not currently strong enough for introduction into clinical practice. However, 60 % respondents’ (CGG = 48 %/BGCS = 71 %, p = 0.009) favoured offering RRSDO to high-risk women declining RRSO, 77 % only supported RRSDO within a clinical trial (CGG = 78 %/BGCS = 76 %) and 81 % (CGG = 76 %/BGCS = 86 %) advocated a UK-wide registry. Vasomotor symptoms (72 %), impact on sexual function (63 %), osteoporosis (59 %), hormonal-therapy (55 %) and subfertility (48 %) related to premature menopause influenced their choice of RRSDO. Potential barriers to offering the two-stage procedure included lack of data on precise level of benefit (83 %), increased surgical morbidity (79 %), loss of breast cancer risk reduction associated with oophorectomy (68 %), need for long-term follow-up (61 %) and a proportion not undergoing DO (66 %). There were variations in perception between BGCS/CGG members which are probably attributable to differences in clinical focus/expertise between these two groups. Despite concerns, there is reasonable support amongst UK clinicians to offering RRSDO to premenopausal high-risk women wishing to avoid RRSO, within a prospective clinical trial.

Background Cervical cancer is the second most common cancer among women up to 65 years of age and is the most frequent cause of death from gynaecological cancers worldwide. Women with International Federation of Gynecology and Obstetrics (FIGO) stage IA2 cervical cancer have measured stromal invasion (when the cancer breaks through the basement membrane of the epithelium) of greater than 3 mm and no greater than 5 mm in depth with a horizontal surface extension of no more than 7 mm. For stage IA2 disease, radical hysterectomy with pelvic lymphadenectomy or radiotherapy is the standard treatment. In order to avoid complications of more radical surgical methods, less invasive options, such as simple hysterectomy, simple trachelectomy or conisation, with or without pelvic lymphadenectomy, may be feasible for stage IA2 disease, considering the relative low risk of local or distant metastatic disease. The evidence for less radical tumour excision and for the role of systematic lymphadenectomy in stage IA2 cervical cancer is not clear. Objectives To evaluate the effectiveness and safety of less radical surgery in stage IA2 cervical cancer. Search methods We searched the Cochrane Gynaecological Cancer Group trials register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to September 2013. We also searched registers of clinical trials and abstracts of scientific meetings. Selection criteria We searched for randomised controlled trials (RCTs) that compared surgical techniques in women with stage IA2 cervical cancer. Data collection and analysis Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, no data were analysed. Main results The search strategy identified 982 unique references, which were all excluded on the basis of title and abstract because it was clear that they did not meet the inclusion criteria. We identified one relevant large ongoing trial, so it is anticipated that we will be able to add this evidence to this review in the future. Authors' conclusions We found no evidence to inform decisions about different surgical techniques in women with stage IA2 cervical cancer. In the future, the results of one large ongoing RCT should allow comparison of different types of surgery.

BACKGROUND: This is an updated version of the original Cochrane review published in The Cochrane Library, Issue 4, 2011. Cervical cancer is the most common cause of death from gynaecological cancers worldwide. Locally advanced cervical cancer, FIGO stage (International Federation of Gynaecology and Obstetrics) equal or more than IB1 is treated with chemotherapy and external beam radiotherapy followed by brachytherapy. If there is metastatic para‐aortic nodal disease, radiotherapy is extended to cover this area. Due to increased morbidity, ideally extended‐field radiotherapy is given only when para‐aortic nodal disease is confirmed. Therefore, accurate assessment of the extent of the disease is very important for planning the most appropriate treatment. OBJECTIVES: To evaluate the effectiveness and safety of pre‐treatment surgical para‐aortic lymph node assessment for woman with locally advanced cervical cancer (FIGO stage IB2 to IVA). SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2012, Issue 10), MEDLINE and EMBASE (up to November 2012). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared surgical para‐aortic lymph node assessment and dissection with radiological staging techniques, in adult women diagnosed with locally advanced cervical cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant trials met the inclusion criteria, abstracted data and assessed risk of bias. One RCT was identified so no meta‐analyses were performed. MAIN RESULTS: We found only one trial, which included 61 women, that met our inclusion criteria. This trial reported data on surgical versus clinical staging and an assessment of the two surgical staging techniques; laparoscopic (LAP) versus extraperitoneal (EXP) surgical staging. The clinical staging was either a contrast‐enhanced computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the abdomen and pelvis to determine nodal status. In this trial, clinical staging appeared to significantly prolong overall and progression‐free survival compared to surgical staging. There was no statistically significant difference in the number of women who experienced severe (grade 3 or 4) toxicity. There was no statistically significant difference in the risk of death, disease recurrence or progression, blood loss, severe toxicity and the duration of the operational procedure between LAP and EXP surgical staging techniques. The strength of the evidence is weak in this review as it is based on one small trial that was at moderate risk of bias. AUTHORS' CONCLUSIONS: Since the last version of this review no new studies were found. From the one available RCT we found insufficient evidence that pre‐treatment surgical para‐aortic lymph node assessment for locally advanced cervical cancer is beneficial, and it may actually have an adverse effect on survival. However, this conclusion is based on analysis of a small single trial and therefore definitive guidance or recommendations for clinical practice cannot be made. Therefore, the decision to offer surgical pre‐treatment assessment of para‐aortic lymph nodes in locally advanced cervical cancer needs to be individualised. The uncertainty regarding any impact on survival from pre‐treatment para‐aortic lymph node assessment should be discussed openly with the women.

Background Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. Objectives To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. Main results We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). Authors' conclusions We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or recurrent endometrial cancer. However, a large number of patients would be needed to demonstrate an effect on survival and none of the included RCTs had a sufficient number of patients to demonstrate a significant difference. In the absence of a proven survival advantage and the heterogeneity of patient populations, the decision to use any type of hormonal therapy should be individualised and with the intent to palliate the disease. It is debatable whether outcomes such as quality of life, treatment response or palliative measures such as relieving symptoms should take preference over overall and PFS as the major objectives of future trials.