>.

Topic proposal .SIGN I understand that this proposal will be retained by the SIGN Programme Lead and be made available on the SIGN website for time period that the proposal is being considered. Only proposals with a completed Declaration of Interests for the principal proposer will bla considered

1. What is the problem/need for a guideline/clinical scenario?

Diagnosis and Management of Endometrial Cancer

2. Burden of the condition

3.

Mortality (from CRUK ) Number of Deaths, Crude and European Age-Standardised(AS) Mortality Rates per 1()O,OOO Population, Females, UK

Deaths Crude Rate AS Rate AS Rate - 95% LCL AS Rate - 95% UCL

Incidence

Eflg la n~ _. __ Wales _. 1,678

6.2 4

3.8 4.2

'120 7.7

4 3.3 4.7

Commonest female gynaecological cancer

Prevalence

Scotland N0I1hern Ire land

194 7.1 4.2

3.6 4.8

Rising due to rise in obesity, increase in elderly population

Variations In practice in Scotland '.

33 3.6 2.5 1.6 3.3

UK 2,025

6.3 4

3.8 4.1

There exists wide variation in diagnostic pathways, imaging (CT vs MRI, role of PET) surgical management (Iaparoscopic versus open, whether lymphadenectomy is performed) and post operative adjuvant therapy.

In health outcomes in Scotland

4. Areas of uncertainty to be covered Key question 1 In women with post-menopausal bleeding what are the best tests to diagnose or exclude endometrial cancer?

Key question 2 \ In women with a diagnosis of endometrial ' cancer, should pelvic or para-aortic lymphadenectomy be carried out.

Key question 3 In women who have had surgical management of endometrial cancer which patients require ,adjuvant radio or chemotherapy?

5. Areas that will not be covered Uterine sarcomas

6. Aspects of the proposed clinical topic that are key areas of' concern for patients, carers and/or the organisations that represent them Across Scotland the waiting times for diagnosis of endometrial cancer are longer than

recommended. There is a need to reduce patient anxiety by improving patient pathways to diagnosis and reassuring women Who do not have cancer. Methods of investigation of PMB vary across Scotland. The withdrawal of a previous SIGN guideline covering management of PMB means there is little guidance for ensuring

. equality and consistency across the country. Publication of guidance will likely lead to greater patient awareness and increase early detection of endometrial cancer.

7. Population Included All women presenting to their GP with PMB. All women with a diagnosis of endometrial cancer. _-

Not included Males !

'w

8. Healthcare setting Included Primary, secondary & tertiary care

Not included

9. Potential Potential to improve current practice A guideline will improve care in surgery (encouraging laparoscopic surgery over open), will set standards for diagnostic testing, and encourage uniformity of practice across the country.

Potential impact on important health outcomes (name measureable indicators) Reduce time to diagnosis. Unknown impact on survival.

Potential impact on resources (name measureable indicators) Unlikely to change resources, but may streamline use of currE~nt services .

10. What evidence based guidance is currently available? None Out-of-date (list) SIGN Publication No. 61 Investigation of Post-Menopausall Bleeding

Current (list) 1. Querleu et al (2011) . Clinical Practice Guidelines for the Management of Patients with

Endometrial cancer in France. Recommendations of the Institut National du Cancer and the Societe Francaise d'Oncologie Gynecologique. International Journal of Gynecological Cancer. .?,945-50.

2. American College of Obstetricians and Gynecologists (2005) . ACOG Practice Bulletin, Clinical Management Guidel ines for Obstetrician-Gynecologists, Number 65, August 2005: Management of Endometrial Cancer. Obstetrics & Gynecology. 106(2L 413-425.

11. Relevance to current Scottish Government policies Detecting Cancer Early

12. Who is this guidance for? GPs, Pratice Nurses, Gynaecologists, Gynaecological Oncologists, Clinical oncologists, Sexual health care physicians and nurses, Radiologists, Ultrasonographers j Trainee doctors i the above specialties.

13. 1m plementation Links with existing audit programmes Links with OPI in Endometrial Cancer

Existing educational initiatives None known

Strategies for monitoring implementation Regional impact assessment

14. Primary contact for topic proposal

Dr Scott Fegan

15. Group(s) or institution(s) supporting th~ proposal

SCAN Network Gynae Group

. Declaration of Interests Please complete all sections and if you have nothing to declare please put 'NIA

Having read the SIGN Policy on Declaration of Competing Interests I declare the following competing interests for the previous year, and the following year. I understand that this declaration will be retained by the SIGN Programme Lead and be made available on the SIGN website for time period that the proposal is being considered. . r:;y--

Signature: t\ k'~ Name: Dr Scon FegiaDJ

Relationship to SIGN: Topic proposal primary contact

Date: If> I oq I f ~ Date received at SIGN:

Personal Interests R f f t emunera Ion rom emp oymen

Name of Employer Nature of Business Self or partnerl Specific? and Post held relative

NHS Lothian, Hospital Doctor Details of Consultant employment hel,d Gynaecological which may be Oncologist significant to, or relevant to, or bear upon the work of SIGN

Remuneration from self employment · Name of Business Nature of Business Self or partner'- Specific?

relative

None Details of self employment held which may be significant to, or relevant to, or bear upon the work of SIGN

Remuneration as holder of paid office Nature of Office Organisation Self or partnerl Specific?

held re~lative ,

None Details of office held which may be significant to, or . . relevant to, or bear upon the work of SIGN

Remuneration as a director of an undertaking Name of Nature of Business Self elr partnerl Specific?

Undertaking rEllative

None Details of directorship held which may be , significant to, or relevant to, or bear upon the work of SIGN

Remuneration as a partner in a firm Name of Nature of Business Self or partnerl Specific?

Partnership relative

None Details of Partnership held which may be significant to, or :

relevant to, or bear upon the work of SIGN '

Shares and securities Description of Description of Self or partner! Specific? organisation nature of holding - relative

(value need not be disclosed)

None Details of interests in shares and securities in commercial healthcare -companies, organisations and undertakings

Remuneration from consultancy or other fee paid work commissioned by, or gifts from, commercial healthcare companies, organisations and undertakings

Nature of work Forwhom Self or partner! Specific? undertaken and relative

frequency

Details of None consultancy or other fee paid work )

which may be significant of to, or relevant to, or bear upon the work of SIGN '

....

Details of gifts which may be significant to, or relevant to, or bear upon the work of SIGN

Non-financial interests Description of interest Self or partner! relative

None Details of non-financial interests which may be significant to, or relevant to, or bear upon the work of SIGN

Non-personal interests Name of company, organisation or

undertaking

Details of non- None personal support from commercial healthcare companies, organisations or undertakings

Signature~. ~~.~1Jf'd\-f---_' _

Thank you for completing this form,

Please return to Roberta James SIGN Programme Lead SIGN Executive, Healthcare Improvement Scotland,

Date:

Gyle Square 11 South Gyle Crescent 1 Edinburgh 1 EH12 9EB

t: 0131 623 4735 e:roberta.james@nhs.net

Data Protection

Specific'?

Nature of interest

Your details will be stored on a database for the purposes of managing this guideline topic proposal. We may retain your details so . that we can contact you about future Healthcare Improvement Scotland activities. We will not pass these details on to any third parties. Please indicate if you do not want your details to be stored after the proposal is published .

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Initial screen

Purpose: initial screening by SIGN Senior Management Team to exclude proposals that are neither clinical, nor multi-professional, nor appropriate for the SIGN process.

1. Is this an appropriate clinical topic for a SIGN guideline? Is it a clinical topic, what is the breadth of the topic and is there a need for the guideline as identified in the proposal?

Yes, although there are concerns that questions 2 and 3 are soecialist while 1 is generalist and how the three questions would sit together in a single guideline. Perhaps it would be more obvious if the questions included outcomes.

2. Is there a suitable alternative product which would address this topic? Would another Healthcare Improvement Scotland product better address the topic?

No, this guideline would partially replace the withdrawn SIGN guideline on post-menopausal bleeding.

3. Has this topic been considered before and rejected? What were the reasons for rejection and are they still applicable

No

4. Outcome Go forward to the next stage of topic selection

YES

Reject

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Scope of recent evidence

Summary: Ten guidelines were identified with publication dates ranging from 2005–2017. The guidelines were from the UK, USA, Canada and Australia. The following topics were covered in the guidelines:

pretreatment evaluation laparoscopic hysterectomy adjuvant hormonal therapy postoperative radiation follow up advanced-stage cancer.

One Health technology assessment from Australia and New Zealand provided evidence for vaginal brachytherapy in women with high-intermediate risk of endometrial cancer. Eight Cochrane reviews provided evidence on:

adjuvant chemotherapy adjuvant radiotherapy hormonal therapy laparoscopy versus laparotomy lymphadenectomy

A further 99 systematic reviews and 521 randomised controlled trials were identified. See Annex 1 for further details

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Annex 1 Scope of recent evidence

Topic: Endometrial Cancer Resources searched: GIN 7 guidelines National Guidelines Clearinghouse – 2 Guidelines NICE 1 IPG Cochrane Library 138 results - 8 relevant reviews CRD databases (includes DARE, HTA, NHS EED) DARE (Up to 2014 only) – 44 relevant reviews NEED (Up to 2014 only) – 26 relevant studies HTA – 1 result (all other results non-english, too old, or broken links/unfindable) INAHTA / UKHTA – Only one item but really old so left out. Medline (SRs only 2014-2017) – 311 sifted to 55 CENTRAL – 521 RCTs (not sifted) Dates searched: 2005-2017 Guidelines 1 AHRQ - Agency for Healthcare Research + Quality. Management of endometrial cancer.

American College of Obstetricians and Gynecologists. NGC:005710. [cited Available from url: http://www.guidelines.gov/summary/summary.aspx?doc_id=10930&nbr=5710

2 AHRQ - Agency for Healthcare Research + Quality. Follow-up after primary therapy for endometrial cancer: a clinical practice guideline. Program in Evidence-based Care. NGC:004867. [cited Available from url: http://www.guideline.gov/summary/summary.aspx?doc_id=8821&nbr=4867

3 AHRQ - Agency for Healthcare Research + Quality. Adjuvant hormonal therapy for stage I endometrial cancer: recommendations. Program in Evidence-based Care. NGC:006237. [cited Available from url: http://www.guideline.gov/summary/summary.aspx?doc_id=12136&nbr=6237

4 AHRQ - Agency for Healthcare Research + Quality. ACR Appropriateness Criteria® pretreatment evaluation and follow-up of endometrial cancer. American College of Radiology. NGC:010172. [cited Available from url: http://www.guideline.gov/content.aspx?id=47687

5 Alberta Provincial Gynecologic Oncology Tumour Team. . Endometrial cancer. [cited Available from url: http://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-gyne002-endometrial.pdf

6 American College of Radiology (ACR). ACR Appropriateness Criteria® advanced stage endometrial cancer. [cited Available from url: https://acsearch.acr.org/docs/3083084/Narrative/

7 ASCO - American Society of Clinical Oncology. Postoperative Radiation Therapy for Endometrial Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline. [cited Available from url: http://www.instituteforquality.org/postoperative-radiation-therapy-endometrial-cancer-american-society-clinical-oncology-clinical

8 ASTRO (US) - American Society for Radiation Oncology. The role of post-operative radiation therapy for endometrial cancer: An ASTRO evidence-based guideline. [cited Available from url: http://www.practicalradonc.org/cms/attachment/2014676400/2036188629/mmc1.pdf

9 CCA - Cancer Council Australia. Clinical Practice Guidelines for the Treatment and Management of Endometrial Cancer. [cited Available from url: http://wiki.cancer.org.au/australia/Guidelines

10 NICE. Laparoscopic hysterectomy (including laparoscopic total hysterectomy and laparoscopically assisted vaginal hysterectomy) for endometrial cancer IPG 356. [cited Available from url: https://www.nice.org.uk/guidance/ipg356

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Health Technology Assessments Australia and New Zealand Horizon scanning Network (2010). Vaginal brachytherapy for treatment of women with high-intermediate risk of endometrial cancer. http://www.horizonscanning.gov.au/internet/horizon/publishing.nsf/Content/C8A5BA60BD01A93ECA257757000A2015/%24File/PS%20Vaginal%20Brachytherapy%20-%20endometrial%20cancer.pdf The included evidence for the safety and effectiveness contained one high-level study (Nout

et al 2010) which indicated VBT has similar oncological and survival outcomes, but lower toxic effects when compared to EBRT. Thus VBT potentially offers improved quality of life for endometrial cancer patients. Importantly, one included study (Byrd et al 2008) reported outcomes and cited further sources which suggest that the benefit of post-operative radiotherapy remains uncertain. Although EBRT and VBT provide similar improvement in vaginal recurrence, it is not clear that this outcome translates to overall or disease-free survival exceeding surgery alone. If radiotherapy is to be performed at all, the indication at present is that prophylactic VBT should be sufficient to reduce the majority of vaginal recurrence following total abdominal hysterectomy with bilateral salpingo-oophorectomy while resulting in fewer toxic effects than EBRT.

Cochrane reviews Frost Jonathan A, Webster Katie E, Bryant A,Morrison J. Lymphadenectomy for the management of endometrial cancer. Cochrane Database of Systematic Reviews. 2015; 9. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007585.pub3/abstract Background: This is an update of a previous Cochrane review published in Issue 1, 2010. The

role of lymphadenectomy in surgical management of endometrial cancer remains controversial. Lymph node metastases can be found in approximately 10% of women who clinically before surgery have cancer confined to the womb. Removal of all pelvic and para-aortic lymph nodes (lymphadenectomy) at initial surgery has been widely advocated, and pelvic and para-aortic lymphadenectomy remains part of the FIGO (International Federation of Gynaecology and Obstetrics) staging system for endometrial cancer. This recommendation is based on data from studies that suggested improvement in survival following pelvic and para-aortic lymphadenectomy. However, these studies were not randomised controlled trials (RCTs), and treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, the Cochrane review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer found no survival advantage. Surgical removal of pelvic and para-aortic lymph nodes has serious potential short-term and long-term sequelae. Therefore it is important to investigate the clinical value of this treatment.Objectives: To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer.Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Gynaecological Cancer Review Group Trials Register, MEDLINE and EMBASE to June 2009 for the original review and extended the search to June 2015 for this version of the review. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field.Selection criteria: RCTs and quasi-RCTs that compared lymphadenectomy versus no lymphadenectomy in adult women diagnosed with endometrial cancer.Data collection and analysis: Two review authors independently extracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy versus those with no lymphadenectomy were pooled in random-effects meta-analyses. We assessed the quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.Main results: Three RCTs met the inclusion criteria; for one small RCT, data were insufficient for inclusion in the meta-analysis. The two RCTs included in the analysis randomly assigned 1945 women, reported HRs for survival adjusted for prognostic factors and based on 1851 women and had an overall low risk of bias, as they satisfied four of the assessment criteria. The third study had an overall unclear risk of bias, as

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information provided was not adequate concerning random sequence generation, allocation concealment, blinding or completeness of outcome reporting.Results of the meta-analysis remain unchanged from the previous version of this review and indicate no differences in overall and recurrence-free survival between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy (pooled HR 1.07, 95% CI 0.81 to 1.43; HR 1.23, 95% CI 0.96 to 1.58 for overall and recurrence-free survival, respectively) (1851 participants, two studies; moderate-quality evidence).We found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy. However, women who underwent lymphadenectomy had a significantly higher risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation than those who did not undergo lymphadenectomy (RR 3.72, 95% CI 1.04 to 13.27; RR 8.39, 95% CI 4.06 to 17.33 for risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation, respectively) (1922 participants, two studies; high-quality evidence).Authors' conclusions: This rev ew found no evidence that lymphadenectomy decreases risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. Evidence on serious adverse events suggests that women who undergo lymphadenectomy are more likely to experience surgery-related systemic morbidity or lymphoedema/lymphocyst formation. Currently, no RCT evidence shows the impact of lymphadenectomy in women with higher-stage disease and in those at high risk of disease recurrence.

Galaal K, Al Moundhri M, Bryant A, Lopes Alberto D,Lawrie Theresa A. Adjuvant chemotherapy for advanced endometrial cancer. Cochrane Database of Systematic Reviews. 2014; 5. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010681.pub2/abstract Background: Approximately 13% of women diagnosed with endometrial cancer present with

advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective.Objectives: To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV).Search methods: We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials.Selection criteria: Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer.Data collection and analysis: Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software.Main results: We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS

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between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison.Authors' conclusions: There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regi ens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.

Galaal K, Bryant A, Fisher Ann D, Al-Khaduri M, Kew F,Lopes Alberto D. Laparoscopy versus laparotomy for the management of early stage endometrial cancer. Cochrane Database of Systematic Reviews. 2012; 9. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006655.pub2/abstract Background: Traditionally, surgery for endometrial cancer (hysterectomy with removal of both

fallopian tubes and ovaries) is performed through laparotomy. It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last 10 to 15 years there has been a steady increase of laparoscopy for endometrial cancer. This review investigates the evidence of benefits and harms of laparoscopic surgery compared with laparotomy for presumed early stage endometrial cancer.Objectives: To compare the overall survival (OS) and disease-free survival (DFS) for laparoscopic surgery versus laparotomy in women with presumed early stage endometrial cancer.Search methods: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2012, MEDLINE, EMBASE and CINAHL up to April 2012. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies. Trial registers we searched included NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocol, as well as abstracts of scientific meetings.Selection criteria: Randomised controlled trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial cancer.Data collection and analysis: We independently abstracted data and assessed risk of bias. Hazard ratios (HRs) were used for OS and recurrence-free survival (RFS), risk ratios (RR) for severe adverse events and the mean difference (MD) method was used for continuous outcomes in women who received laparoscopy or laparotomy and these were then pooled in random-effects meta-analyses.Main results: Eight RCTs comparing laparoscopy with laparotomy for the surgical management of early stage endometrial cancer were identified.All eight trials met the inclusion criteria, 3644 women were assessed at the end of the trials. Three trials assessing 359 participants with early stage endometrial cancer, found no statistically significant difference in the risk of death and disease or recurrence between women who underwent laparoscopy and those who underwent laparotomy (HR = 1.14, 95% confidence interval (CI): 0.62 to 2.10) and HR = 1.13, 95% CI: 0.90 to 1.42 for OS and RFS respectively). There was no statistically significant difference in the rate of peri-operative death, women requiring a blood transfusion, and bladder, ureteric, bowel and vascular injury. However, a meta-analysis of two trials found that women in the laparoscopy group lost significantly less blood than those in the laparotomy group (MD = -106.82 mL, 95% CI: -141.59 to -72.06). A further meta-analysis of two trials, which assessed 2923 women and included one very large trial of over 2500 participants, found that the rate of severe post-operative adverse events was significantly lower in the laparoscopy group compared with the laparotomy group (RR = 0.58, 95% CI: 0.37 to 0.91). The large trial did not give a breakdown of these severe post-operative adverse events into different adverse event categories. Most trials were at moderate risk of bias. Hospital stay was reported in all of the trials and results show that on average, laparoscopy was associated with a significantly shorter hospital stay.Authors' conclusions: This review has found evidence to support the role of laparoscopy for the management of early endometrial cancer.For presumed early stage primary endometrioid adenocarcinoma of the endometrium, laparoscopy is associated with similar overall and disease-free survival. Laparoscopy is associated with reduced operative morbidity and

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hospital stay. There is no significant difference in severe post-operative morbidity between the two modalities.

Johnson N, Bryant A, Miles T, Hogberg T,Cornes P. Adjuvant chemotherapy for endometrial cancer after hysterectomy. Cochrane Database of Systematic Reviews. 2011; 10. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003175.pub2/abstract Background: Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining

(endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer.Objectives: To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer.Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, 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) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment.Data collection and analysis: We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse.Main results: Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly favouring the addition of postoperative platinum based chemotherapy. The HR for progression-free survival is 0.75 (0.64 to 0.89). This means that chemotherapy reduces the risk of being dead at any censorship by a quarter. Chemotherapy reduces the risk of developing the first recurrence outside the pelvis (RR = 0.79 (0.68 to 0.92), 5% absolute risk reduction; NNT = 20). The analysis of pelvic recurrence rates is underpowered but the trend suggests that chemotherapy may be less effective than radiotherapy in a direct comparison (RR = 1.28 (0.97 to 1.68)) but it may have added value when used with radiotherapy (RR = 0.48 (0.20 to 1.18)).Authors' conclusions: Postoperative platinum based chemotherapy is associated with a small benefit in progression-free survival and overall survival irrespective of radiotherapy treatment. It reduces the risk of developing a metastasis, could be an alternative to radiotherapy and has added value when used with radiotherapy.

Kokka F, Brockbank E, Oram D, Gallagher C,Bryant A. Hormonal therapy in advanced or recurrent endometrial cancer. Cochrane Database of Systematic Reviews. 2010; 12. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007926.pub2/abstract 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

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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.

Kong A, Johnson N, Kitchener Henry C,Lawrie Theresa A. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database of Systematic Reviews. 2012; 4. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003916.pub4/abstract Background: This is an updated version of the original Cochrane review published in Issue 2,

2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial.Objectives: To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer.Search methods: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update.Selection criteria: We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer.Data collection and analysis: Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1.Main results: We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95% CI 0.83 to 1.15) or improved endometrial cancer-related survival (time-to-event data: five trials, 2965 women; HR 0.96, 95% CI 0.72 to 1.28; and dichotomous data: seven trials, 3628 women; RR 1.02, 95% CI 0.81 to 1.29) or improved distant recurrence rates (dichotomous data: seven trials, 3628 women; RR 1.04, 95% CI 0.80 to1.35).EBRT did not improve survival outcomes in either the intermediate-risk or high-risk subgroups, although high-risk data were limited, and a benefit of EBRT for high-risk women could not be excluded. One trial (PORTEC-2) compared EBRT with VBT in the high-intermediate risk group and reported that VBT was effective in ensuring vaginal control with a non-significant difference in loco-regional relapse rate compared to EBRT (5.1% versus 2.1%; HR 2.08, 95% CI 0.71 to 6.09; P = 0·17). In the subgroup of low-risk patients (IA/B and grade 1/2), EBRT increased the risk of endometrial carcinoma-related deaths (including treatment-related deaths) (two trials, 517 women; RR 2.64, 95% CI 1.05 to 6.66) but there was a lack of data on overall survival. We considered the evidence for the low-risk subgroup to be of a low quality.EBRT was associated with significantly increased severe acute toxicity (two trials, 1328 patients, RR 4.68, 95% CI 1.35 to 16.16), increased severe late toxicity (six trials, 3501 women; RR 2.58, 95% CI 1.61 to 4.11) and significant reductions in quality of life scores and rectal and bladder function more than 10 years after randomisation (one trial, 351 women) compared with no EBRT.One trial of VBT versus no additional treatment in women with low-risk lesions reported a non-significant reduction in locoregional recurrence in the VBT

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group compared with the no additional treatment group (RR 0.39, (95% CI 0.14 to 1.09). There were no significant differences in survival outcomes in this trial.Authors' conclusions: EBRT reduces the risk of locoregional recurrence but has no significant impact on cancer-related deaths or overall sur ival. It is associated with significant morbidity and a reduction in quality of life. There is no demonstrable survival advantage from adjuvant EBRT for high-risk stage I endometrial cancer, however, the meta-analyses of this subgroup were underpowered and also included high-intermediate risk women, therefore we cannot exclude a small benefit in the high-risk subgroup. EBRT may have an adverse effect on endometrial cancer survival when used to treat uncomplicated low-risk (IA/B grade 1/2) endometrial cancer. For the intermediate to high-intermediate risk group, VBT alone appears to be adequate in ensuring vaginal control compared to EBRT. Further research is needed to guide practice for lesions that are truly high risk. In addition, the definitions of risk should be standardised.

Martin-Hirsch Pierre PL, Bryant A, Keep Sarah L, Kitchener Henry C,Lilford R. Adjuvant progestagens for endometrial cancer. Cochrane Database of Systematic Reviews. 2011; 6. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001040.pub2/abstract Background: Endometrial cancer is the most common genital tract carcinoma among women

in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease.Objectives: To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer.Search methods: We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009.Selection criteria: Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer.Data collection and analysis: Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses. .Main results: Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27).Authors' conclusions: There is no evidence to support the use of adjuvant progestagen therapy in the primary treatment of endometrial cancer. There have now been several RCTs which have failed to establish a role for adjuvant progestagen therapy after primary treatment for endometrial cancer and therefore, further trials in this field are probably not justified.

Vale Claire L, Tierney J, Bull Sarah J,Symonds Paul R. Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma. Cochrane Database of Systematic Reviews. 2012; 8. [cited: url: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003915.pub4/abstract Background: Although endometrial adenocarcinoma is a common gynaecological cancer, a

comparatively small proportion of patients present with, or develop, recurrent or advanced disease. However, for those women whose disease does progress or recur the prognosis is poor and the best treatment is yet to be identified. Co-morbidity, including obesity and cardiac disease, and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.Objectives: To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.Search methods: Systematic searches of MEDLINE, EMBASE, CENTRAL and the Cochrane Gynaecological Cancer specialist trials register were conducted to identify all eligible randomised controlled trials (RCTs).Databases were searched from 1966 to January 2012. Literature searches were supplemented with searches of relevant trials registers and conference proceedings.Selection criteria: RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced

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disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded.Data collection and analysis: Data were extracted from the papers by review authors and authors of included studies contacted for further information.Main results: Fourteen eligible trials, which recruited patients between 1974 and 2005, were identified, eight of which compared 'more' with 'less' chemotherapy. Results from these eight trials, including 1519 patients, showed that treatment consisting of 'more' chemotherapy was associated with longer overall survival (OS) (hazard ratio (HR) 0.86; 95% confidence intervals (CI) 0.77 to 0.96; P = 0.005) and with longer progression-free survival (PFS) (n = 1526; HR 0.82; 95% CI 0.74 to 0.90; P < 0.0001). However, serious acute toxicities were more common in women randomised to the more-intense chemotherapy regimens.There was no evidence to suggest that any particular doublet chemotherapy was better (or worse) than any other, or that any single-agent chemotherapy was better (or worse) than another; however, data for these two comparisons were limited. There were no comparative trials of chemotherapy with endocrine therapy or best supportive care alone.Authors' conclusions: This review suggests that more-intense chemotherapy regimens may improve both OS and PFS for women with advanced or recurrent endometrial cancer. However, owing to inconsistencies between cytotoxic drug combinations that have been assessed in randomised trials to date, the optimum regimen has still to be defined. Future trials should aim to include measures of quality of life (QoL) and symptom control in addition to survival and progression outcomes.

Other Systematic reviews 1 Abdullah NA, Huang KG, Casanova J, Artazcoz S, Jarruwale P, Benavides DR, et al. Sentinel

lymph node in endometrial cancer: a systematic review on laparoscopic detection (Provisional abstract). Gynecology and Minimally Invasive Therapy 2013; 2: 75-8.

2 Alcazar JL, Dominguez-Piriz J, Juez L, Caparros M, Jurado M. Intraoperative Gross Examination and Intraoperative Frozen Section in Patients With Endometrial Cancer for Detecting Deep Myometrial Invasion: A Systematic Review and Meta-analysis. International Journal of Gynecological Cancer 2016;26(2):407-15.

3 Alcazar JL, Orozco R, Martinez-Astorquiza Corral T, Juez L, Utrilla-Layna J, Minguez JA, et al. Transvaginal ultrasound for preoperative assessment of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis. Ultrasound in Obstetrics & Gynecology 2015;46(4):405-13.

4 Andreano A, Rechichi G, Rebora P, Sironi S, Valsecchi MG, Galimberti S. MR diffusion imaging for preoperative staging of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis. European Radiology 2014;24(6):1327-38.

5 Ansari M, Ghodsi Rad MA, Hassanzadeh M, Gholami H, Yousefi Z, Dabbagh VR, et al. Sentinel node biopsy in endometrial cancer: systematic review and meta-analysis of the literature (Provisional abstract). European Journal of Gynaecological Oncology 2013; 34: 387-401.

6 Barlin JN, Puri I, Bristow RE. Cytoreductive surgery for advanced or recurrent endometrial cancer: a meta-analysis (Structured abstract). Gynecologic Oncology 2010; 118: 14-8.

7 Bie Y, Zhang Z. Diagnostic value of serum HE4 in endometrial cancer: a meta-analysis. World Journal of Surgical Oncology 2014;12:169.

8 Bie Y, Zhang Z, Wang X. Adjuvant chemo-radiotherapy in the "sandwich" method for high risk endometrial cancer--a review of literature. BMC Women's Health 2015;15:50.

9 Bogliolo S, Gardella B, Dominoni M, Musacchi V, Cassani C, Zanellini F, et al. Effectiveness of aromatase inhibitors in the treatment of advanced endometrial adenocarcinoma. Archives of Gynecology & Obstetrics 2016;293(4):701-8.

10 Bollineni VR, Ytre-Hauge S, Bollineni-Balabay O, Salvesen HB, Haldorsen IS. High Diagnostic Value of 18F-FDG PET/CT in Endometrial Cancer: Systematic Review and Meta-Analysis of the Literature. Journal of Nuclear Medicine 2016;57(6):879-85.

11 Bourdel N, Chauvet P, Tognazza E, Pereira B, Botchorishvili R, Canis M. Sampling in Atypical Endometrial Hyperplasia: Which Method Results in the Lowest Underestimation of Endometrial Cancer? A Systematic Review and Meta-analysis. Journal of Minimally Invasive Gynecology 2016;23(5):692-701.

12 Bourgin C, Saidani M, Poupon C, Cauchois A, Foucher F, Leveque J, et al. Endometrial cancer in elderly women: Which disease, which surgical management? A systematic review of the literature. European Journal of Surgical Oncology 2016;42(2):166-75.

13 Bouwman F, Smits A, Lopes A, Das N, Pollard A, Massuger L, et al. The impact of BMI on

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surgical complications and outcomes in endometrial cancer surgery--an institutional study and systematic review of the literature. Gynecologic Oncology 2015;139(2):369-76.

14 Breijer MC, Peeters JA, Opmeer BC, Clark TJ, Verheijen RH, Mol BW, et al. Capacity of endometrial thickness measurement to diagnose endometrial carcinoma in asymptomatic postmenopausal women: a systematic review and meta-analysis (Structured abstract). Ultrasound in Obstetrics and Gynecology 2012; 40: 621-9.

15 Carey MS, Gawlik C, Fung-Kee-Fung M, Chambers A, Oliver T. Systematic review of systemic therapy for advanced or recurrent endometrial cancer (Provisional abstract). Gynecologic Oncology 2006; 101: 158-67.

16 Chang MC, Chen JH, Liang JA, Yang KT, Cheng KY, Kao CH. 18F-FDG PET or PET/CT for detection of metastatic lymph nodes in patients with endometrial cancer: a systematic review and meta-analysis (Provisional abstract). European Journal of Radiology 2012; 81: 3511-7.

17 Chang YN, Zhang Y, Wang YJ, Wang LP, Duan H. Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer cells: a meta-analysis (Provisional abstract). Fertility and Sterility 2011; 96: 957-61.e2.

18 Chen SH, Li ZA, Huang R, Xue HQ. Robot-assisted versus conventional laparoscopic surgery for endometrial cancer staging: A meta-analysis. Taiwanese Journal of Obstetrics & Gynecology 2016;55(4):488-94.

19 Chen Y, Ren YL, Li N, Yi XF, Wang HY. Serum human epididymis protein 4 vs. carbohydrate antigen 125 and their combination for endometrial cancer diagnosis: a meta-analysis. European Review for Medical & Pharmacological Sciences 2016;20(10):1974-85.

20 Chen Z, Wang SH, Zhou J, Wu T, Li J. Contribution of PGR genetic polymorphisms to the pathogenesis of endometrial cancer: A meta-analysis. Journal of Cancer Research & Therapeutics 2015;11(4):810-7.

21 Cheng D, Sun Y, He H. Diagnostic role of circulating YKL-40 in endometrial carcinoma patients: a meta-analysis of seven related studies. Medical Oncology 2014;31(12):326.

22 Clark LH, Soper JT. Endometrial Cancer and the Role of Lymphadenectomy. Obstetrical & Gynecological Survey 2016;71(6):353-60.

23 Collaborative Group on Epidemiological Studies on Endometrial C. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncology 2015;16(9):1061-70.

24 Cormier B, Rozenholc AT, Gotlieb W, Plante M, Giede C, Communities of Practice Group of Society of Gynecologic Oncology of C. Sentinel lymph node procedure in endometrial cancer: A systematic review and proposal for standardization of future research. Gynecologic Oncology 2015;138(2):478-85.

25 Das SK, Niu XK, Wang JL, Zeng LC, Wang WX, Bhetuwal A, et al. Usefulness of DWI in preoperative assessment of deep myometrial invasion in patients with endometrial carcinoma: a systematic review and meta-analysis. Cancer Imaging 2014;14:32.

26 de Rijk SR, Steenbergen ME, Nieboer TE, Coppus SF. Atypical Endometrial Polyps and Concurrent Endometrial Cancer: A Systematic Review. Obstetrics & Gynecology 2016;128(3):519-25.

27 Deng L, Wang QP, Chen X, Duan XY, Wang W, Guo YM. The Combination of Diffusion- and T2-Weighted Imaging in Predicting Deep Myometrial Invasion of Endometrial Cancer: A Systematic Review and Meta-Analysis. Journal of Computer Assisted Tomography 2015;39(5):661-73.

28 Diaz-Padilla I, Romero N, Amir E, Matias-Guiu X, Vilar E, Muggia F, et al. Mismatch repair status and clinical outcome in endometrial cancer: A systematic review and meta-analysis (Provisional abstract). Critical Reviews in Oncology/Hematology 2013; 88: 154-67.

29 Gala RB, Margulies R, Steinberg A, Murphy M, Lukban J, Jeppson P, et al. Systematic review of robotic surgery in gynecology: robotic techniques compared with laparoscopy and laparotomy. Journal of Minimally Invasive Gynecology 2014;21(3):353-61.

30 Gao H, Zhang Z. Sequential chemotherapy and radiotherapy in the sandwich method for advanced endometrial cancer: a meta-analysis. Medicine 2015;94(16):e672.

31 Ghooshkhanei H, Treglia G, Sabouri G, Davoodi R, Sadeghi R. Risk stratification and prognosis determination using (18)F-FDG PET imaging in endometrial cancer patients: a systematic review and meta-analysis. Gynecologic Oncology 2014;132(3):669-76.

32 Gkrozou F, Dimakopoulos G, Vrekoussis T, Lavasidis L, Koutlas A, Navrozoglou I, et al. Hysteroscopy in women with abnormal uterine bleeding: a meta-analysis on four major endometrial pathologies. Archives of Gynecology & Obstetrics 2015;291(6):1347-54.

33 Granado de la Orden S, Reza MM, Blasco JA, Andradas E, Callejo D, Perez T. Laparoscopic

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hysterectomy in the treatment of endometrial cancer: a systematic review (Structured abstract). Journal of Minimally Invasive Gynecology 2008; 15: 395-401.

34 Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. International Journal of Gynaecology & Obstetrics 2015;131(3):234-9.

35 Gu H, Li J, Gu Y, Tu H, Zhou Y, Liu J. Survival Impact of Ovarian Preservation on Women With Early-Stage Endometrial Cancer: A Systematic Review and Meta-analysis. International Journal of Gynecological Cancer 2017;27(1):77-84.

36 Gupta V, McGunigal M, Prasad-Hayes M, Kalir T, Liu J. Adjuvant radiation therapy is associated with improved overall survival in high-intermediate risk stage I endometrial cancer: A national cancer data base analysis. Gynecologic Oncology 2017;144(1):119-24.

37 Hanna TP, Delaney GP, Barton MB. The population benefit of radiotherapy for gynaecological cancer: Local control and survival estimates. Radiotherapy & Oncology 2016;120(3):370-7.

38 He HY, Zeng DY, Ou HL, Tang YZ, Li JJ, Zhong H. Laparoscopic treatment of endometrial cancer: systematic review (Structured abstract). Journal of Minimally Invasive Gynecology 2013; 20: 413-23.

39 Hu L, Du S, Guo W, Chen D, Li Y. Comparison of Serum Human Epididymis Protein 4 and Carbohydrate Antigen 125 as Markers in Endometrial Cancer: A Meta-Analysis.[Erratum appears in Int J Gynecol Cancer. 2016 May;26(4):807]. International Journal of Gynecological Cancer 2016;26(2):331-40.

40 Humber CE, Tierney JF, Symonds RP, Collingwood M, Kirwan J, Williams C, et al. Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration (Structured abstract). Annals of Oncology 2007; 18: 409-20.

41 Iavazzo C, Gkegkes ID. Port-site metastases in patients with gynecological cancer after robot-assisted operations. Archives of Gynecology & Obstetrics 2015;292(2):263-9.

42 Iavazzo C, Gkegkes ID. Robotic assisted hysterectomy in obese patients: a systematic review. Archives of Gynecology & Obstetrics 2016;293(6):1169-83.

43 Iavazzo C, Gkegkes ID, Vrachnis N. Early recurrence of early stage endometrioid endometrial carcinoma: possible etiologic pathways and management options. Maturitas 2014;78(3):155-9.

44 Johnson N, Cornes P. Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis (Provisional abstract). BJOG. An International Journal of Obstetrics and Gynaecology 2007; 114: 1313-20.

45 Joo WD, Schwartz PE, Rutherford TJ, Seong SJ, Ku J, Park H, et al. Microscopic Omental Metastasis in Clinical Stage I Endometrial Cancer: A Meta-analysis. Annals of Surgical Oncology 2015;22(11):3695-700.

46 Ju W, Myung SK, Kim Y, Choi HJ, Kim SC. Comparison of laparoscopy and laparotomy for management of endometrial carcinoma: a meta-analysis (Structured abstract). International Journal of Gynecological Cancer 2009; 19: 400-6.

47 Kadkhodayan S, Shahriari S, Treglia G, Yousefi Z, Sadeghi R. Accuracy of 18-F-FDG PET imaging in the follow up of endometrial cancer patients: systematic review and meta-analysis of the literature (Provisional abstract). Gynecologic Oncology 2013; 128: 397-404.

48 Kakhki VR, Shahriari S, Treglia G, Hasanzadeh M, Zakavi SR, Yousefi Z, et al. Diagnostic performance of fluorine 18 fluorodeoxyglucose positron emission tomography imaging for detection of primary lesion and staging of endometrial cancer patients: systematic review and meta-analysis of the literature (Provisional abstract). International Journal of Gynecological Cancer 2013; 23: 1536-43.

49 Kamalpour L, Brindise RT, Nodzenski M, Bach DQ, Veledar E, Alam M. Primary cutaneous mucinous carcinoma: a systematic review and meta-analysis of outcomes after surgery. JAMA Dermatology 2014;150(4):380-4.

50 Kang S, Yoo HJ, Hwang JH, Lim MC, Seo SS, Park SY. Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies (Structured abstract). Gynecologic Oncology 2011; 123: 522-7.

51 Kassem L, Abdel-Rahman O. Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data. Critical Reviews in Oncology-Hematology 2016;108:1-12.

52 Kim HS, Suh DH, Kim MK, Chung HH, Park NH, Song YS. Systematic lymphadenectomy for survival in patients with endometrial cancer: a meta-analysis (Structured abstract). Japanese Journal of Clinical Oncology 2012; 42: 405-12.

53 Klopp A, Smith BD, Alektiar K, Cabrera A, Damato AL, Erickson B, et al. The role of

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postoperative radiation therapy for endometrial cancer: executive summary of an American society for radiation oncology evidence-based guideline (Provisional abstract). Database of Abstracts of Reviews of Effects 2014; 137-44.

54 Koskas M, Uzan J, Luton D, Rouzier R, Darai E. Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis. Fertility & Sterility 2014;101(3):785-94.

55 Koutoukidis DA, Knobf MT, Lanceley A. Obesity, diet, physical activity, and health-related quality of life in endometrial cancer survivors. Nutrition Reviews 2015;73(6):399-408.

56 Latif NA, Haggerty A, Jean S, Lin L, Ko E. Adjuvant therapy in early-stage endometrial cancer: a systematic review of the evidence, guidelines, and clinical practice in the U.S. Oncologist 2014;19(6):645-53.

57 Lee B, Suh DH, Kim K, No JH, Kim YB. Influence of positive peritoneal cytology on prognostic factors and survival in early-stage endometrial cancer: a systematic review and meta-analysis. Japanese Journal of Clinical Oncology 2016;46(8):711-7.

58 Li MY, Hu XX, Zhong JH, Chen LL, Lin YX. Therapeutic role of systematic lymphadenectomy in early-stage endometrial cancer: A systematic review. Oncology Letters 2016;11(6):3849-57.

59 Lin F, Zhang QJ, Zheng FY, Zhao HQ, Zeng QQ, Zheng MH, et al. Laparoscopically assisted versus open surgery for endometrial cancer: a meta-analysis of randomized controlled trials (Structured abstract). International Journal of Gynecological Cancer 2008; 18: 1315-25.

60 Lin Y, Zhou J, Cheng Y, Zhao L, Yang Y, Wang J. Comparison of Survival Benefits of Combined Chemotherapy and Radiotherapy Versus Chemotherapy Alone for Uterine Serous Carcinoma: A Meta-analysis. International Journal of Gynecological Cancer 2017;27(1):93-101.

61 Lukka H, Chambers A, Fyles A, Thephamongkhol K, Fung-Kee-Fung M, Elit L, et al. Adjuvant radiotherapy in women with stage I endometrial cancer: a systematic review (Provisional abstract). Gynecologic Oncology 2006; 102: 361-8.

62 Luomaranta A, Leminen A, Loukovaara M. Magnetic resonance imaging in the assessment of high-risk features of endometrial carcinoma: a meta-analysis. International Journal of Gynecological Cancer 2015;25(5):837-42.

63 Matsuo K, Moeini A, Machida H, Scannell CA, Casabar JK, Kakuda M, et al. Tumor Characteristics and Survival Outcome of Endometrial Cancer Arising in Adenomyosis: An Exploratory Analysis. Annals of Surgical Oncology 2016;23(3):959-67.

64 Mavromatis ID, Antonopoulos CN, Matsoukis IL, Frangos CC, Skalkidou A, Creatsas G, et al. Validity of intraoperative gross examination of myometrial invasion in patients with endometrial cancer: a meta-analysis (Structured abstract). Acta Obstetricia et Gynecologica Scandinavica 2012; 91: 779-93.

65 Nevis IF, Vali B, Higgins C, Dhalla I, Urbach D, Bernardini MQ. Robot-assisted hysterectomy for endometrial and cervical cancers: a systematic review. Journal of Robotic Surgery 2016;16:16.

66 Orekoya O, Samson ME, Trivedi T, Vyas S, Steck SE. The Impact of Obesity on Surgical Outcome in Endometrial Cancer Patients: A Systematic Review. Journal of Gynecologic Surgery 2016;32(3):149-57.

67 Palomba S, Falbo A, Mocciaro R, Russo T, Zullo F. Laparoscopic treatment for endometrial cancer: a meta-analysis of randomized controlled trials (RCTs) (Structured abstract). Gynecologic Oncology 2009; 112: 415-21.

68 Park D. Clinical Effectiveness And Safety Of Robot-Assisted Laparoscopic Hysterectomy Versus Traditional Laparotomy For Endometrial Cancer: A Systematic Review. Value in Health 2015;18(7):A433.

69 Park DA, Lee DH, Kim SW, Lee SH. Comparative safety and effectiveness of robot-assisted laparoscopic hysterectomy versus conventional laparoscopy and laparotomy for endometrial cancer: A systematic review and meta-analysis. European Journal of Surgical Oncology 2016;42(9):1303-14.

70 Park HJ, Nam EJ, Kim S, Kim YB, Kim YT. The benefit of adjuvant chemotherapy combined with postoperative radiotherapy for endometrial cancer: a meta-analysis (Provisional abstract). Database of Abstracts of Reviews of Effects 2013; 39-44.

71 Pelikan HM, Trum JW, Bakers FC, Beets-Tan RG, Smits LJ, Kruitwagen RF. Diagnostic accuracy of preoperative tests for lymph node status in endometrial cancer: a systematic review (Provisional abstract). Cancer Imaging 2013; 13: 314-22.

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72 Polyzos NP, Mauri D, Tsioras S, Messini CI, Valachis A, Messinis IE. Intraperitoneal dissemination of endometrial cancer cells after hysteroscopy: a systematic review and meta-analysis (Structured abstract). International Journal of Gynecological Cancer 2010; 20: 261-7.

73 Polyzos NP, Pavlidis N, Paraskevaidis E, Ioannidis JP. Randomized evidence on chemotherapy and hormonal therapy regimens for advanced endometrial cancer: an overview of survival data (Structured abstract). European Journal of Cancer 2006; 42: 319-26.

74 Qin Y, Yu Z, Yang J, Cao D, Yu M, Wang Y, et al. Oral Progestin Treatment for Early-Stage Endometrial Cancer: A Systematic Review and Meta-analysis. International Journal of Gynecological Cancer 2016;26(6):1081-91.

75 Ran L, Jin J, Xu Y, Bu Y, Song F. Comparison of robotic surgery with laparoscopy and laparotomy for treatment of endometrial cancer: a meta-analysis. PLoS ONE [Electronic Resource] 2014;9(9):e108361.

76 Rocha A, Dominguez AM, Lecuru F, Bourdel N. Indocyanine green and infrared fluorescence in detection of sentinel lymph nodes in endometrial and cervical cancer staging - a systematic review. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2016;206:213-9.

77 Ruscito I, Gasparri ML, Braicu EI, Bellati F, Raio L, Sehouli J, et al. Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes-A Meta-Analysis. Annals of Surgical Oncology 2016;23(11):3749-56.

78 Secord AA, Hasselblad V, Von Gruenigen VE, Gehrig PA, Modesitt SC, Bae-Jump V, et al. Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis. Gynecologic Oncology 2016;140(1):184-90.

79 Selman TJ, Mann CH, Zamora J, Khan KS. A systematic review of tests for lymph node status in primary endometrial cancer (Structured abstract). BMC Women's Health 2008; 8:8:

80 Shim SH, Lee SJ, Kim SN. Effects of hormone replacement therapy on the rate of recurrence in endometrial cancer survivors: a meta-analysis. European Journal of Cancer 2014;50(9):1628-37.

81 Singh SS, Scott S, Bougie O, Leyland N, Committee SCP-G, Leyland N, et al. Technical update on tissue morcellation during gynaecologic surgery: its uses, complications, and risks of unsuspected malignancy.[Erratum appears in J Obstet Gynaecol Can. 2015 Feb;37(2):107]. Journal of Obstetrics & Gynaecology Canada: JOGC 2015;37(1):68-81.

82 Smith AJ, Fader AN, Tanner EJ. Sentinel Lymph Node Assessment in Endometrial Cancer: A Systematic Review and Meta-analysis. American Journal of Obstetrics & Gynecology 2016;18:18.

83 Smits A, Lopes A, Bekkers R, Galaal K. Body mass index and the quality of life of endometrial cancer survivors--a systematic review and meta-analysis. Gynecologic Oncology 2015;137(1):180-7.

84 Smits A, Lopes A, Das N, Bekkers R, Massuger L, Galaal K. The effect of lifestyle interventions on the quality of life of gynaecological cancer survivors: A systematic review and meta-analysis. Gynecologic Oncology 2015;139(3):546-52.

85 Timmermans A, Opmeer BC, Khan KS, Bachmann LM, Epstein E, Clark TJ, et al. Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis (Structured abstract). Obstetrics and Gynecology 2010; 116: 160-7.

86 Upala S, Anawin S. Bariatric surgery and risk of postoperative endometrial cancer: a systematic review and meta-analysis. Surgery for Obesity & Related Diseases 2015;11(4):949-55.

87 van der Steen-Banasik E, Christiaens M, Shash E, Coens C, Casado A, Herrera FG, et al. Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma. European Journal of Cancer 2016;65:172-81.

88 van Hanegem N, Prins MM, Bongers MY, Opmeer BC, Sahota DS, Mol BW, et al. The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2016;197:147-55.

89 Wang D, Ma CL, Ye YZ, Srijana S. Clinical effectiveness and safety of laparoscopy versus laparotomy for endometrial cancer: a meta-analysis (Provisional abstract). Chinese Journal of Evidence-Based Medicine 2013; 13: 596-604.

90 Wang HL, Ren YF, Yang J, Qin RY, Zhai KH. Total laparoscopic hysterectomy versus total abdominal hysterectomy for endometrial cancer: a meta-analysis (Structured abstract). Asian

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carcinoma: a systematic review (Provisional abstract). Chinese Journal of Evidence-Based Medicine 2008; 8: 244-51.

92 Wei DM, Mei L, Fang F, Wu TX, Liu GJ. Adjuvant radiotherapy for endometrial cancer: a systematic review (Provisional abstract). Chinese Journal of Evidence-Based Medicine 2009; 9: 465-75.

93 White ID, Sangha A, Lucas G, Wiseman T. Assessment of sexual difficulties associated with multi-modal treatment for cervical or endometrial cancer: A systematic review of measurement instruments. Gynecologic Oncology 2016;143(3):664-73.

94 Wiltink LM, Nout RA, Fiocco M, Meershoek-Klein Kranenbarg E, Jurgenliemk-Schulz IM, Jobsen JJ, et al. No Increased Risk of Second Cancer After Radiotherapy in Patients Treated for Rectal or Endometrial Cancer in the Randomized TME, PORTEC-1, and PORTEC-2 Trials. Journal of Clinical Oncology 2015;33(15):1640-6.

95 Wu LM, Xu JR, Gu HY, Hua J, Haacke EM, Hu J. Predictive value of T2-weighted imaging and contrast-enhanced MR imaging in assessing myometrial invasion in endometrial cancer: a pooled analysis of prospective studies (Provisional abstract). European Radiology 2013; 23: 435-49.

96 Xie W, Cao D, Yang J, Shen K, Zhao L. Robot-assisted surgery versus conventional laparoscopic surgery for endometrial cancer: a systematic review and meta-analysis. Journal of Cancer Research & Clinical Oncology 2016;142(10):2173-83.

97 Zhang H, Cui J, Jia L, Hong S, Kong B, Li D. Comparison of laparoscopy and laparotomy for endometrial cancer (Structured abstract). International Journal of Gynecology and Obstetrics 2012; 116: 185-91.

98 Zhang ZJ, Li S. The prognostic value of metformin for cancer patients with concurrent diabetes: a systematic review and meta-analysis. Diabetes, Obesity & Metabolism 2014;16(8):707-10.

99 Zullo F, Falbo A, Palomba S. Safety of laparoscopy vs laparotomy in the surgical staging of endometrial cancer: a systematic review and metaanalysis of randomized controlled trials (Structured abstract). American Journal of Obstetrics and Gynecology 2012; 207: 94-100.

CENTRAL search for RCTs 521 – number only. Not sifted for relevance.