Esther L. Moss

Patient acceptability of circulating tumour DNA testing in endometrial cancer follow‐up

Abstract Objective Circulating tumour DNA (ctDNA) is emerging as a potential option to detect disease recurrence in many cancer types, however, ensuring patient acceptability of changing clinical practice and the introduction of new technology is paramount. Methods Patients enrolled in a non‐intervention cohort study determining the ability of ctDNA to detect recurrent endometrial cancer (EC) were invited to participate in a semi‐structured interview. Analysis was performed by Template Analysis. Results Eighteen patients were interviewed. A ctDNA blood test was viewed by participants as more physically and psychologically acceptable than clinical examination to monitor for EC recurrence. In particular, participants expressed overwhelming preference for a blood test rather than pelvic examination. Although participants acknowledged that an abnormal ctDNA result could cause anxiety, they expressed a preference to be informed of their results, even if a recurrence was too small to detect radiologically. Explanations for these opinions were a desire for certainty whether their cancer would recur or not, and knowledge would help them be more aware of symptoms that should be reported to their clinician. Conclusions ctDNA monitoring to identify EC recurrence appears to be acceptable to patients, and for many, it may be preferable to clinical examination.

Risk Stratified Follow-Up for Endometrial Cancer: The Clinicians’ Perspective

Risk-stratified follow-up for endometrial cancer (EC) is being introduced in many cancer centres; however, there appears to be diversity in the structure and availability of schemes across the UK. This study aimed to investigate clinicians’ and clinical specialist nurses’ (CNS) experiences of follow-up schemes for EC, including patient-initiated follow-up (PIFU), telephone follow-up (TFU) and clinician-led hospital follow-up (HFU). A mixed-methods study was conducted, consisting of an online questionnaire to CNSs, an audience survey of participants attending a national “Personalising Endometrial Cancer Follow-up” educational meeting, and qualitative semi-structured telephone interviews with clinicians involved in the follow-up of EC. Thematic analysis identified three main themes to describe clinicians’ views: appropriate patient selection; changing from HFU to PIFU schemes; and the future of EC follow-up schemes. Many participants reported that the COVID-19 pandemic impacted EC follow-up by accelerating the transition to PIFU/TFU. Overall, there was increasing support for non-HFU schemes for patients who have completed primary treatment of EC; however, barriers were identified for non-English-speaking patients and those who had communication challenges. Given the good long-term outcome associated with EC, greater focus is needed to develop resources to support patients post-treatment and individualise follow-up according to patients’ personal needs and preferences.

Innovative Follow-up Strategies for Endometrial Cancer

Increasing recognition of the heterogeneous nature of endometrial cancer, the excellent prognosis of low-risk cases and improvements in risk stratification offer opportunities for innovative, personalised follow-up strategies. This review article outlines the evidence base for alternative follow-up strategies in the different risk categories of endometrial cancer, cancer survivorship programmes and considers future directions in endometrial cancer follow-up, including emerging new techniques, such as the liquid biopsy, and opportunities for combining molecular and clinicopathological features to personalise endometrial cancer follow-up.

Economic evaluation of different routes of surgery for the management of endometrial cancer: a retrospective cohort study

ObjectivesThe benefits of minimally invasive surgery (MIS) for endometrial carcinoma (EC) are well established although the financial impact of robotic-assisted hysterectomy (RH) compared with laparoscopic hysterectomy (LH) is disputed.DesignRetrospective cohort study.SettingEnglish National Health Service hospitals 2011–2017/2018.Participants35 304 women having a hysterectomy for EC identified from Hospital Episode Statistics.Primary and secondary outcome measuresThe primary outcome was the association between route of surgery on cost at intervention, 30, 90 and 365 days for women undergoing an open hysterectomy (OH) or MIS (LH/RH) for EC in England. The average marginal effect was calculated to compare RH versus OH and RH versus LH which adjusted for any differences in the characteristics of the surgical approaches. Secondary outcomes were to analyse costing data for each surgical approach by age, Charlson Comorbidity Index (CCI) and hospital MIS rate classification.ResultsA total of 35 304 procedures were performed, 20 405 (57.8%) were MIS (LH: 18 604 and RH: 1801), 14 291 (40.5%) OH. Mean cost for LH was significantly less than RH, whereas RH was significantly less than OH at intervention, 30, 90 and 365 days (p<0.001). Over time, patients who underwent RH had increasing CCI scores and by the 2015/2016 year had a higher average CCI than LH. Comparing the cost of LH and RH against CCI score identified that the costs closely reflected the patients’ CCI. Increasing disparity was also seen between the MIS and OH costs with rising age. When exploring the association between provider volume, MIS rate and surgical costs, there was an association with the higher the MIS rate the lower the average cost.ConclusionsFurther research is needed to investigate costs in matched patient cohorts to determine the optimum surgical modality in different populations.

Surgical trends, outcomes and disparities in minimal invasive surgery for patients with endometrial cancer in England: a retrospective cohort study

Objective To examine surgical outcomes and trends in the implementation of minimally invasive surgery (MIS) use for endometrial cancer (EC). Design Retrospective cohort study. Setting English National Health Service hospitals 2011–2017/2018. Population 35 304 patients having a hysterectomy for EC identified from Hospital Episode Statistics. Methods Univariate and multivariate analyses compared MIS to open hysterectomy (OH) by assessing the association between demographic, clinical and hospital characteristics by using logistic regression. A propensity score was created, to control for confounding factors including demographics, clinical and hospital characteristics, from a logistic regression which enabled the inverse probability weighting of treatment to be applied in order to compare outcomes of treatment. Main outcome measures The association between route of surgery on perioperative morbidity and mortality. Results The MIS rate rose from 40.3% in 2011 to 68.7% in 2017/2018, however, there was significant geographical variation (p<0.001). The overall 90-day mortality was significantly higher with OH versus MIS (OR 0.34, 95% CI 0.18 to 0.62, p=0.0002). MIS rates were significantly lower in patients from the lowest socioeconomic group (LSEG) compared with patients from the highest group (HSEG) (55.4% vs 59.9%, p<0.01), and in the black population as compared with white and Asian populations (40.4% vs 58.6% and 56.0%, p<0.0001). When patients from LSEG and black patients were treated in hospitals with high MIS rates, the MIS rate increased close to that of the HSEG and white patients (81.0% and 74.1% vs 83.2% and 82.6%). Conclusions Further investigation is needed to understand the barriers to MIS and improve access so that as many patients as possible can benefit from the reduced morbidity/mortality associated with MIS.

Patient-initiated follow-up for low-risk endometrial cancer: a cost-analysis evaluation

Risk stratification has resulted in patient-initiated follow-up being introduced for low-risk endometrial cancer in place of routine hospital follow-up. The financial benefit to the patient and the healthcare economy of patient-initiated follow-up, as compared with hospital follow-up, has yet to be explored. In this study, we explored the potential impact for both the healthcare economy and patients of patient-initiated follow-up. Women diagnosed with low-risk endometrial cancer enrolled on a patient-initiated follow-up scheme between November 2014 and September 2018 were included. Data on the number of telephone calls to the nurse specialists and clinic appointments attended were collected prospectively. The number of clinic appointments that would have taken place if the patient had continued on hospital follow-up, rather than starting on patient-initiated follow-up, was calculated and costs determined using standard National Health Service (NHS) reference costs. The time/distance traveled by patients from their home address to the hospital clinic was calculated and used to determine patient-related costs. A total of 187 patients with a median of 37 (range 2-62) months follow-up after primary surgery were enrolled on the scheme. In total, the cohort were scheduled to attend 1673 appointments with hospital follow-up, whereas they only attended 69 clinic appointments and made 107 telephone contacts with patient-initiated follow-up. There was a 93.5% reduction in costs from a projected £194 068.00 for hospital follow-up to £12 676.33 for patient-initiated follow-up. The mean patient-related costs were reduced by 95.6% with patient-initiated follow-up. The total mileage traveled by patients for hospital follow-up was 30 891.4 miles, which was associated with a mean traveling time per patient of 7.41 hours and clinic/waiting time of 7.5 hours compared with 1165.8 miles and 0.46 hours and 0.5 hours, respectively, for patient-initiated follow-up. The introduction of a patient self-management follow-up scheme for low-risk endometrial cancer was associated with financial/time saving to both the patient and the healthcare economy as compared with hospital follow-up.

Patient-derived explants, xenografts and organoids: 3-dimensional patient-relevant pre-clinical models in endometrial cancer

The majority of endometrial cancers are detected early with a favourable prognosis. However, for patients with advanced disease, chemotherapy response rates and overall survival remains poor. The endometrial cancer population is typically elderly with multiple co-morbidities and aggressive cytotoxic therapy may be hazardous. Therefore, there is an urgent need to define optimal treatment strategies for advanced and recurrent disease and personalise therapy based on individual tumour and patient characteristics. Three-dimensional (3D) models that preserve the tumour microenvironment and tumour-stromal interactions are increasingly important for translational research with the advent of immunotherapy and molecularly targeted agents. 3D patient-relevant pre-clinical models in endometrial cancer include spheroids, patient-derived organoids, microfluidic systems, patient-derived xenografts and patient-derived explants. Here we present a review of available 3D modelling systems in endometrial cancers, highlighting their current use, advantages, disadvantages and applications to translational research with a focus on the power of the patient-derived explant platform.

Development of a blood test for uterine sarcoma—Diagnosis and monitoring (DOORS-D and DOORS-M) studies

Uterine sarcomas can be difficult to differentiate from uterine fibroids due to many shared symptoms and imaging features, which can result in delayed or missed diagnosis, or over treatment. The ‘Development of a blood test for uterine Sarcoma – Diagnosis’ (DOORS-D) (ISRCTN14800787) and ‘Development of a blood test for uterine Sarcoma – Monitoring’ (DOORS-M) (ISRCTN14174468) studies aim to explore the role for circulating tumour DNA (ctDNA) to diagnose and to monitor uterine sarcomas. DOORS-D will recruit patients who have a suspected uterine sarcoma or large fibroid and are due to undergo surgery (hysterectomy or myomectomy) for a blood sample prior to surgery whereas DOORS-M will recruit patients who have been diagnosed with a uterine sarcoma in the previous 10 years for longitudinal blood sampling every 3–6 months over the course of the study. Information will be collated on patient characteristics and symptoms, tumour characteristics and diagnostic imaging, with representative images selected and analysed using large language models. Analysis of genomic/methylation profile of ctDNA samples collected from DOORS-M will be used to design a ctDNA-based ‘test’. Analysis of the samples collected from the participants recruited to the DOORS-D study will enable the accuracy of the ‘test’ to differentiate uterine sarcomas from fibroids to be determined. In addition, the opinions of patients with a suspected or confirmed sarcoma will be explored through semi-structured qualitative interviews. Purposeful recruitment strategy will ensure that the experiences of women from diverse socioeconomic, cultural and ethnic backgrounds are included. The results of the studies will be shared through conference presentations and peer-reviewed publications.

Identification of European-wide clinical priorities for guideline development in the management of pre-invasive cervical disease

Addressing management controversies in the treatment of pre-invasive cervical disease is a key priority for the European Federation for Colposcopy/European Society of Gynaecologic Oncology who aim to develop a practical handbook of European centred guidelines to address areas where there is a lack of high-quality evidence or identifiable practice variation. Clinical opinion across the EFC network was sought to identify topics likely to have the most impact on clinical practice for systematic review and development of practice recommendations. A scoping exercise comprising of a three-iteration modified Delphi with representation from each member society of the EFC was conducted in 2018. Round one identified 19 potential topics which were scored for importance using a five-point Likert scale by EFC members in round two and ranked. Results from round two were discussed at an open EFC satellite meeting resulting in exclusion of five topics. A third round of the 14 remaining topics was conducted to allow members to modify scores after viewing the second-round rankings. Responses were analysed and topics were allocated a weighted score. Strategies for management of persistent HPV infection in the context of normal colposcopy and negative cytology was the highest overall weighted topic (4.40) followed by identification of appropriate length of follow up for ASCUS or LSIL prior to excisional treatment (3.95) and the impact of length of excision on patient outcomes (3.95). Topics to identify best practice for management of challenging topics scored highly including optimising follow up strategies for cervical stenosis (3.91) and management of HSIL in the under 25 year olds (3.64) or pregnancy (3.64). A European wide systematic modified-Delphi has prioritised six topics for systematic review and generation of clinical practice recommendations aiming to assist management in areas of controversy in pre-invasive cervical disease.

ACCEPTANCE: protocol for a feasibility study of a multicomponent physical activity intervention following treatment for cervical cancer

Introduction Cervical cancer treatment can have life changing sequelae and be associated with poor short-term and long-term quality of life. Physical activity (PA; that is, bodily movement) is known to improve health outcomes and quality of life for cancer survivors, both physically and psychologically. To date, no interventions to increase PA following cervical cancer have been evaluated. This study aims to (1) determine the feasibility of conducting a PA intervention after cervical cancer and (2) to explore the acceptability of the programme and evaluation measures. Methods and analysis The design is a pre study and post study design. Thirty participants aged between 18 and 60 years from the Midlands region, UK, who have completed primary treatment for cervical cancer at least 6 months previously and do not meet the national PA guidelines will be recruited. Identification of potential participants will take place through the University Hospitals of Leicester National Health Service (NHS) Trust. Participants will receive an intervention focused on increasing PA through the provision of education, action planning, goal setting, problem solving and self-monitoring of PA behaviour, particularly steps per day. Device assessed PA and questionnaires will be completed at baseline, week 6, week 12 and week 24. Feasibility will be assessed in terms of recruitment, retention, attrition, completion of measures and intervention compliance, for which specific feasibility criteria have been established. The process evaluation will explore the experiences and acceptability of the intervention components and evaluation measures. Ethics and dissemination Ethical approval has been granted by the West of Scotland Research Ethics Committee 1 for this study. Results will inform intervention refinement for the design of a definitive pilot trial. These results will be disseminated via peer-reviewed publications and international conferences while input from a patient and public involvement (PPI) group will inform effective ways to circulate results among the wider community. Trial registration number ISRCTN16349793 , Registered 30 September 2020.

Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer

Abstract Purpose Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. Methods A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. Results In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. Discussion This study provides important insights into patients’ views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.

Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.