• Scottish Intercollegiate Guidelines Network (SIGN). Epithelial ovarian cancer. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Oct. 36 p. (SIGN publication; no. 75). [182 references]

Epithelial ovarian cancer

Note: The management of borderline tumours is not included within these recommendations.

Diagnosis
Evaluation
Management
Screening
Treatment

Colon and Rectal Surgery
Family Practice
Internal Medicine
Medical Genetics
Obstetrics and Gynecology
Oncology
Pathology
Radiology
Surgery

Advanced Practice Nurses
Allied Health Personnel
Clinical Laboratory Personnel
Nurses
Pharmacists
Physician Assistants
Physicians

To provide evidence-based recommendations for the screening, diagnosis and management of patients with epithelial ovarian cancer

Women with epithelial ovarian cancer

Screening

1. Family history
2. Genetic testing
3. Prophylactic oophorectomy
4. Counselling and support services

Diagnosis

Primary care

1. Evaluation of signs and symptoms
2. Serum CA125

Secondary care

1. Ultrasound
2. Risk of malignancy index (RMI)
3. Computed tomography (CT) after ultrasound

Management

Surgical

1. Colonic surgery
   • Preoperative bowel preparation
   • Stoma counseling and marking
2. Venous thromboembolic (VTE) prophylaxis with unfractionated heparin (UFH) or low molecular weight heparin (LMWH)
3. Preoperative serum CA125 levels, alpha fetoprotein (AFP), and human chorionic gonadotropin (hCG)
   • Assessment of carcinoembryonic antigen (CEA) is considered but not recommended
4. Intraoperative frozen section assessment
5. Comprehensive staging
6. Fertility conserving surgery (unilateral salpingo-oophorectomy)
7. Aggressive surgical cytoreduction
8. Optimal cytoreduction
9. Interval debulking surgery (IDS)
10. Specialist nursing involvement

Chemotherapy

1. Adjuvant chemotherapy in early stage disease (carboplatin)
2. Neoadjuvant chemotherapy
3. Platinum agents (cisplatin & carboplatin)
4. Taxanes (paclitaxel)
5. Cyclophosphamide
6. Anthracyclines (doxorubicin)
7. Topoisomerase inhibitors (topotecan)
8. Tamoxifen
9. Erythropoietin for chemotherapy-related anemia
10. Intraperitoneal chemotherapy
11. Patient education on adverse effects of chemotherapy
12. Administration of chemotherapy

Management of malignant bowel obstruction in relapsed disease

1. Surgery
2. Non-surgical management
   • Pharmacological
     • Corticosteroids
     • Antiemetics
     • Antisecretory
     • Analgesics

Patient management

1. Specialist palliative care
2. Patient education
3. Referral for counselling

• Accuracy of diagnostic tests
• Overall survival rates
• Response rates
• Progression-free survival rates
• Disease-free survival rates
• Quality of life
• Adverse effects of treatment (e.g., toxicity)

Searches of Electronic Databases

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Levels of Evidence

1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias

1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2++: High quality systematic reviews of case control or cohort studies; high quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+: Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal

3: Non-analytic studies, e.g. case reports, case series

4: Expert opinion

Review of Published Meta-Analyses
Systematic Review

Expert Consensus

The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.

A: At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results

B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++

D: Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

The national open meeting is the main consultative phase of Scottish Intercollegiate Guidelines Network (SIGN) guideline development, at which the guideline development group presents their draft recommendations for the first time. The national open meeting for this guideline was held in June 2002 and was attended by representatives of all key specialties relevant to the guideline. The draft guideline was also available on the SIGN website for a limited period at this stage to allow those unable to attend the meeting to contribute to the development of the guideline.

Four general practitioners were also invited to review the draft guideline but did not submit any comments.

As a final quality control check, the guideline is reviewed by an Editorial Group comprising the relevant specialty representatives on SIGN Council to ensure that the peer reviewers’ comments have been addressed adequately and that any risk of bias in the guideline development process as a whole has been minimised.

Note from the Scottish Intercollegiate Guidelines Network (SIGN) and National Guideline Clearinghouse (NGC): In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.

The strength of recommendation grading (A-D) and level of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) are defined at the end of the "Major Recommendations" field.

Screening

D - Screening for ovarian cancer in high risk groups should only be offered in the context of a research study designed to gather data on:

• sensitivity and specificity of the screening tool
• The International Federation of Gynaecology and Obstetrics (FIGO) stages of cancers detected through screening
• residual risk of primary peritoneal cancer following prophylactic oophorectomy

D - Screening programmes for women at increased risk of ovarian cancer should include mechanisms for providing emotional and psychological support.

C - Women with genetic mutations of BRCA1 or BRCA2 genes should be counselled regarding prophylactic oophorectomy and removal of Fallopian tubes at a relevant time of their life.

Diagnosis

D - Women with a pelvic mass should be referred to gynaecology irrespective of the CA125 test result.

C - The risk of malignancy index (RMI) scoring system is the method of choice for predicting whether or not an ovarian mass is likely to be malignant.

C - Women with a risk of malignancy index score >200 should be referred to a centre with experience in ovarian cancer surgery.

Surgery

C - Preoperative bowel preparation in ovarian cancer patients should be undertaken where clinical findings and imaging reveal that advanced disease with bowel involvement is present.

B - Patients for whom preoperative bowel preparation is indicated should see a trained stoma nurse for counselling and potential stoma site marking.

D - Serum CA125 levels are useful in predicting disease bulk and should be assayed preoperatively in women with pelvic masses.

D - Routine preoperative carcinoembryonic antigen (CEA) estimation should not be performed in patients with ovarian cancer.

D - To minimise the need for a second operative staging procedure, intraoperative frozen section assessment can be used to diagnose malignancy and to exclude metastatic disease.

In Advanced Disease

C - If aggressive cytoreduction is not possible then optimal cytoreduction is the recommended surgical procedure if performance status allows this to take place.

D - Patients with stage III disease should be operated on by a gynaecological oncologist rather than a general gynaecologist or general surgeon.

C - Interval debulking surgery is recommended, if performance status allows, where there is evidence of response to chemotherapy as determined by CA125 and imaging.

Chemotherapy

B - Carboplatin can be offered to all early stage epithelial ovarian cancer patients.

In Advanced Disease

A - First line chemotherapy treatment of epithelial ovarian cancer should include a platinum agent either in combination or as a single agent, unless specifically contraindicated.

A - Carboplatin is the platinum drug of choice in both single and combination therapy.

A - Paclitaxel is recommended in combination therapy with platinum in the first line postsurgery treatment of epithelial ovarian cancer where the potential benefits justify the toxicity of the therapy.

A - Patients who choose less toxic therapy or who are unfit for taxanes should be offered single agent carboplatin.

A - Cyclophosphamide is not recommended in the first line chemotherapy treatment of epithelial ovarian cancer.

A - The use of anthracyclines in first line chemotherapy treatment of epithelial ovarian cancer is not recommended outside randomised controlled trials (RCTs).

In Relapsed Disease

B - Chemotherapy for recurrent ovarian cancer should be regarded as palliative in intent and should be reserved for symptomatic recurrence of disease.

B - Symptomatic platinum-sensitive cancer recurrence can be treated with further platinum and paclitaxel.

C - Tamoxifen should be considered in patients for whom chemotherapy is not appropriate.

B - If erythropoietin is used to treat anaemia it should only be when the haemoglobin concentration is <10 g/dL and the dose should not exceed 450 units/kg/week.

D - Staff should be experienced, trained in the safe administration of chemotherapy, and involved in ongoing continuing professional development (CPD) and reappraisal.

D – Hospital-based administration of chemotherapy should take place during the working day in designated areas equipped to deal with any medical emergencies.

D - Women should be given accurate information on their likely response to chemotherapy, including adverse effects, so that they can make an informed decision about whether or not to proceed with treatment.

D - The impact of chemotherapy toxicities on patients’ quality of life must be balanced against their anticipated response to treatment.

C - Clinical trials should have appropriate inclusion criteria and should incorporate recognised standard treatment.

Management of Malignant Bowel Obstruction

C - Surgery for malignant bowel obstruction in patients with advanced ovarian cancer must be justified on the basis of achieving a significant benefit.

C - Symptoms of bowel obstruction can be relieved by using the following drug categories either alone or in combination:

• antiemetic
• antisecretory
• analgesic
• corticosteroids

Specialist Palliative Care

B - Patients with advanced ovarian cancer require a coordinated, multiprofessional approach with access to a specialist palliative care team.

D - Patients with persistent poorly controlled symptoms should be referred to specialist palliative care.

Information for Patients

C - Patients should be offered verbal and written information throughout their journey of care and should be made aware of the support mechanisms that are in place and how to access them.

C - Structured emotional support should be available to all patients and carers.

Definitions:

Grades of Recommendation

A: At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results

B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++

D: Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Levels of Evidence

1++: High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias

1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2++: High quality systematic reviews of case control or cohort studies; high quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+: Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal

3: Non-analytic studies, e.g. case reports, case series

4: Expert opinion

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

• Improved screening, diagnosis and management of epithelial ovarian cancer
• Reduced surgical complications
• Improved response to treatment
• Improved survival (overall, progression-free, and disease-free)
• Improved patient quality of life including:
  • Better symptom control
  • Structured emotional support

• False positive results from screening
• Surgical complications
• Side effects associated with chemotherapy including:
  • Anaemia
  • Deterioration in quality of life

Contraindications to surgery for malignant bowel obstruction in patients with advanced ovarian cancer

Absolute contraindications:

• Patient refusal
• Previous abdominal surgery which showed diffuse metastatic cancer
• Involvement of proximal stomach
• Intra-abdominal carcinomatosis demonstrated radiologically with a contrast study revealing a severe motility problem
• Diffuse palpable intra-abdominal masses (having excluded faecal masses)
• Massive ascites which rapidly recurs after drainage

Relative contraindications:

• Non-symptomatic extensive extra-abdominal malignant disease (e.g., widespread metastases and pleural effusion)
• Poor general performance status
• Poor nutritional status (e.g., marked weight loss/cachexia, marked hypoalbuminaemia, and low lymphocyte count)
• Severe cachexia
• Small bowel obstruction
• Previous radiotherapy of the abdomen or pelvis

This guideline is not intended to be construed or to serve as a standard of medical care. Standards of care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge and technology advance and patterns of care evolve. These parameters of practice should be considered guidelines only. Adherence to them will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor, following discussion of the options with the patient, in light of the diagnostic and treatment choices available. It is advised however that significant departures from the national guideline or any local guidelines derived from it should be fully documented in the patient’s case notes at the time the relevant decision is taken.

Implementation of national clinical guidelines is the responsibility of local National Health System (NHS) organizations and is an essential part of clinical governance. It is acknowledged that not every guideline can be implemented immediately on publication, but mechanisms should be in place to ensure that the care provided is reviewed against the guideline recommendations and the reasons for any differences assessed and, where appropriate, addressed. These discussions should involve both clinical staff and management. Local arrangements may then be made to implement the national guideline in individual hospitals, units and practices, and to monitor compliance. This may be done by a variety of means including patient-specific reminders, continuing education and training, and clinical audit.

Living with Illness

Effectiveness
Patient-centeredness

• Scottish Intercollegiate Guidelines Network (SIGN). Epithelial ovarian cancer. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Oct. 36 p. (SIGN publication; no. 75). [182 references]

Not applicable: The guideline was not adapted from another source.

2003 Oct

Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]

Scottish Executive Health Department

Not stated

Guideline Development Group: Dr Nadeem Siddiqui (Chairman), Consultant Gynaecologist and Oncologist, Stobhill Hospital, Glasgow; Dr Chris Hardwick (Secretary), Specialist Registrar in Obstetrics and Gynaecology, North Glasgow Hospitals National Health System (NHS) Trust; Dr Ian Aitken, General Practitioner, Glasgow; Mr Andrew Anderson, National Coordinator, Maggie’s Centres, Western General Hospital, Edinburgh; Mr Roger Black, Head, Scottish Cancer Intelligence Unit, Information and Statistics Division (ISD), Common Services Agency, Edinburgh; Ms Sandra Bredin, Clinical Nurse Specialist, Stobhill Hospital, Glasgow; Mrs Anne Coote, Patient Helpline Coordinator, Argyll and Clyde Health Council, Paisley; Mrs Inez Crow, District Nurse, Falkirk; Ms Linda Davidson, Staff Nurse, Crosshouse Hospital, Kilmarnock; Dr Heather Deans, Consultant Radiologist, Aberdeen Royal Infirmary; Dr Sonia Devereux, General Practitioner, Forfar; Mr Craig Eriksen, Consultant Colorectal Surgeon, Perth Royal Infirmary; Dr Marie Fallon, Senior Lecturer in Palliative Medicine, Western General Hospital, Edinburgh; Dr Hani Gabra, Consultant in Medical Oncology, Western General Hospital, Edinburgh; Professor David Hole, Professor of Epidemiology and biostatistics, West of Scotland Cancer Surveillance Unit, Department of Public Health, University of Glasgow; Dr Brian Magowan, Consultant Gynaecologist, Borders General Hospital, Melrose; Mrs Jean McAllister, Principal Biochemist, North Glasgow University Hospitals NHS Trust; Dr David W. M. Millan, Consultant in Pathology, Western Infirmary, Glasgow; Miss Kath Nattress, Macmillan Clinical Nurse Specialist, Western General Hospital, Edinburgh; Dr David Parkin, Consultant Gynaecological Oncologist, Aberdeen Royal Infirmary; Mr Mark Parsons, Principal Clinical Pharmacist, Ninewells Hospital, Dundee; Dr Denny Phillips, Consultant Gynaecologist, Perth Royal Infirmary; Dr Nicholas Reed, Clinical Director, Beatson Oncology Centre, Glasgow; Mr Duncan Service, Information Services, Scottish Intercollegiate Guidelines Network; Dr Sally Stearns, Health Economist, Health Economics Research Unit, University of Aberdeen; Professor Michael Steele, Professor in Medical Science, University of St. Andrews; Mrs Diane Stirling, Macmillan Clinical Nurse Specialist, Western General Hospital, Edinburgh; Ms Joanne Topalian, Programme Manager, SIGN; Dr Sara Twaddle, Health Economist, North Glasgow Hospital NHS Trust

All members of the Scottish Intercollegiate Guidelines Network (SIGN) guideline development groups are required to complete a declaration of interests, both personal and non-personal. A personal interest involves payment to the individual concerned (e.g., consultancies or other fee-paid work commissioned by or shareholdings in the pharmaceutical industry); a non-personal interest involves payment which benefits any group, unit or department for which the individual is responsible (e.g., endowed fellowships or other pharmaceutical industry support). Details of the declarations of interest of any guideline development group member(s) are available from the Scottish Intercollegiate Guidelines Network executive.

This NGC summary was completed by ECRI on May 3, 2004. The information was verified by the guideline developer on July 15, 2004. This summary was updated by ECRI on January 29, 2007, following the U.S. Food and Drug Administration advisory on erythropoiesis stimulating agents. This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on July 9, 2007, following the FDA advisory on erythropoiesis stimulating agents. This summary was updated by ECRI Institute on March 13, 2008 following the updated FDA advisory on heparin sodium injection. This summary was updated by ECRI Institute on March 21, 2008 following the FDA advisory on Erythropoiesis Stimulating Agents. This summary was updated by ECRI Institute on August 15, 2008 following the U.S. Food and Drug Administration advisory on Erythropoiesis Stimulating Agents (ESAs).