Jo Morrison

Working together to shape the endometrial cancer research agenda: The top ten unanswered research questions

BACKGROUND Endometrial cancer (EC) is the most common gynaecological cancer in developed nations and its incidence is rising. As a direct consequence, more women are dying from EC despite advances in care and improved survivorship. There is a lack of research activity and funding, as well as public awareness about EC. We sought to engage patients, carers and healthcare professionals to identify the most important unanswered research questions in EC. METHODOLOGY The priority setting methodology was developed by the James Lind Alliance and involved four key stages: gathering research questions; checking these against existing evidence; interim prioritisation; and a final consensus meeting during which the top ten unanswered research questions were agreed using modified nominal group methodology. RESULTS Our first online survey yielded 786 individual submissions from 413 respondents, of whom 211 were EC survivors or carers, and from which 202 unique unanswered research questions were generated. 253 individuals, including 108 EC survivors and carers, completed an online interim prioritisation survey. The resulting top 30 questions were ranked in a final consensus meeting. Our top ten spanned the breadth of patient experience of this disease and included developing personalised risk scoring, refining criteria for specialist referral, understanding the underlying biology of different types of EC, developing novel personalised treatment and prevention strategies, prognostic and predictive biomarkers, increasing public awareness and interventions for psychological issues. CONCLUSION Having established the top ten unanswered research questions in EC, we hope this galvanises researchers, healthcare professionals and the public to collaborate, coordinate and invest in research to improve the lives of women affected by EC.

Lymphadenectomy for Treatment of Early-Stage Endometrial Cancer.

Clinical Question What is the association between lymphadenectomy and survival, disease recurrence, and surgical morbidity in women with presumed early-stage, low-grade endometrial carcinoma? Bottom Line The evidence from randomized clinical trials suggests that lymphadenectomy does not improve survival or decrease disease recurrence in women with early-stage, low-grade endometrial carcinoma. Furthermore lymphadenectomy is associated with an increase in both short- and long-term surgery-related systemic morbidity.

British Gynaecological Cancer Society (BGCS) epithelial ovarian/fallopian tube/primary peritoneal cancer guidelines: recommendations for practice

The remit of this guideline is to collate and propose evidencebased guidelines for the management of epithelial ovarian-type cancers (ovary, fallopian tube or peritoneal origin) and borderline tumours. This document covers all epithelial cancers with any j) GC and GT then made changes based on peer review comments; k) 4th draft was sent back to council for approval; l) 4th draft was sent to BGCS members for feedback; m) GC and GT then made changes based on members’ feedback; n) 5th draft was sent to public consultation including patient support groups; o) GCand GT thenmade changesbased onnon-members’ feedback; p) Final draft approved by council and officers.

Spotlight on … gynaecological cancer

In the 3 years since the last ‘Spotlight on . . . gynaecological cancer’ (TOG 2014;16:231) there have been several new TOG articles, which have been added to the Gynaecological Cancer collection on the TOG website for specialists’ CPD and review. Increasingly, subspecialist gynaecological oncologists, and medical and clinical oncologists deliver gynaecological cancer care. However, patients often present via other routes, hence why these new articles are also useful reading for the general obstetrician and gynaecologist, with topics ranging from human papillomavirus (HPV) in cervical cancer screening, new insights into ovarian cancer development and genetics, changes to surgical practice, and palliative care.

Borderline ovarian tumours: balancing risks of recurrence over decades

Borderline ovarian tumours account for 10–15% of epithelial tumours. Women affected are on average 10 years younger than those with invasive ovarian epithelial tumours (Morice et al. Lancet Oncol 2012;13:103–15) and many will have fertility as a major concern. Often women are unexpectedly diagnosed after conservative surgery, following either cystectomy or unilateral oophorectomy. Frozen section can be useful for intra-operative management (Ratnavelu et al. Cochrane Database Syst Rev 2016;(3): CD010360), informing a conservative surgical approach of a suspicious mass. However, what should we do about staging, if the diagnosis was unsuspected, and about management of remaining ovarian tissue, in the short and longer term? In this issue Ouldamer et al. analysed outcomes of 360 women with borderline tumours and devised a risk scoring system for recurrence. This may help patients when considering whether to have further surgery or fertility-conservation. However, it has a few major limitations. The results have not been externally validated in a separate patient population, posing a significant challenge to the validity and applicability of the conclusions. Another limitation is the median follow up of 60 months. Borderline tumours can recur decades after the initial diagnosis, so recurrence risks in this study are likely to be an underestimate of the longer term risks. In addition, hazard ratios of several variables (age, serous histology, age), incorporated into the multivariate analysis, have wide confidence intervals that cross 1. This implies that factors may not be independently significant, perhaps due to sample size, length of follow up and small number of recurrences. Previous studies have examined risks of recurrence and survival after a diagnosis of a borderline ovarian tumour. A nationwide study from Denmark of 1042 women, confirmed after central review of histology, diagnosed between 1978 and 2002, found that extra-ovarian implants, especially invasive implants, were associated with an increase in recurrence and reduction in overall survival (Hannibal et al. Gynecol Oncol 2014;134:267–73). The ROBOTS study of 950 German women, diagnosed between 1998 and 2008 (Trilsch et al. Ann Oncol 2014;25:1320-7), found that extraovarian implants, incomplete staging surgery, fertility-preservation and residual macroscopic tumour were associated with relapse. As yet there are no data for overall survival. However, of the 74 women who relapsed, 30% had invasive disease (2.3% of all women), although this was less frequent in women <40 years of age at diagnosis compared with those >40 (12.0 versus 66.7%, P < 0.001). The scoring system in this issue (Ouldamer et al. BJOG 2017;124: 935–42) should be tested in these large independent patient cohorts. Further information about histological and molecular risk factors are to be expected from ROBOTS and other on-going studies, although, as studies need prolonged follow-up periods, this is likely to be sometime hence. In the meantime, our recommendations should acknowledge the limitations in data that inform us. Current data suggest that completion surgery should be offered, especially in women who have finished their families. Younger women appear to have lower risk of malignant transformation in conserved ovaries, although the risk of recurrent borderline tumours in conserved ovaries is high, especially after cystectomy.

Current management of ovarian carcinoma

Epithelial ovarian cancer is a common gynecologic malignancy with an increasing incidence possibly due to the spread of ‘Westernized’ lifestyles. Currently most women present at an advanced stage, and despite radical surgery and chemotherapy, will eventually die from their disease. This article aims to review current surgical and medical management of women with ovarian cancer and the evidence which supports it. Finally, there will be a brief discussion of some of the novel therapies in development.