CTF Structured Abstract: Screening for ovarian cancer

Canadian Task Force on Preventive Health Care

Structured Abstract

Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made. (Formerly, these situations were captured under a "C Recommendation".) This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade. For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.

Screening for Ovarian Cancer

Prepared by Cindy Quinton Gladstone, MHSc, MD, FRCPC, Research Associate, Department of Preventive Medicine and Biostatistics, University of Toronto, Ontario

These recommendations were finalized by the Task Force in January 1994

Contents

Objective

Burden of Suffering

Options

Outcomes

Evidence

Values

Benefits, Harms, and Costs

Recommendations

Validation

Sponsors

Selected References

Objective

To make recommendations about screening for ovarian cancer in pre- and post-menopausal asymptomatic women, and women with a familial history of ovarian cancer in Canada.

Burden of Suffering

Ovarian cancer is the sixth most common female malignancy, after cancers of the breast, colon, lung, and uterus. The estimated incidence in Canada in 1993 was approximately 2100 new cases per year, about 4% of all new cancers in women. Yet, because it is so lethal, it remains the leading cause of gynecologic cancer mortality in both Canada and the U.S. Risk factors for ovarian cancer include familial history (familial instances account for 5-15% of all ovarian cancers), advanced age, low parity, and nonuse of the oral contraceptive pill. At least one case-control report has shown a protective effect after as little as 3 - 6 months of oral contraceptive use.

At present, because of late and nonspecific symptomatology, and the relative inaccessibility of the ovaries to physical examination, only 25% of women with ovarian cancer have disease confined to the ovary at the time of diagnosis. While in recent studies the five-year survival rate for this group nears 90%, the comparable rate is 35% or worse for the majority of women, who have disseminated disease when diagnosed.

Options

Screening measures included pelvic examination, abdominal ultrasound, transvaginal sonography (TVS), serum antigen CA 125 and combinations of ł 2 measures.

Outcomes

Sensitivity and specificity of screening measures; 5-year disease-free survival; adverse effects of screening.

Evidence

MEDLINE was searched from 1975 forward to January 1994 using the MeSH headings "screening", "ovarian neoplasms" and 1 of either "ultrasonography", "CA125 antigen", "neoplasms-staging", "surgery", "chemotherapy" or "radiotherapy". Articles in languages other than English, review articles and those dealing with advanced stages of cancer or nonepithelial tumours were excluded. Content experts were consulted to ensure inclusion of all relevant papers.

Recommendations were graded as:

A Good evidence to support the recommendation that the condition be specifically considered in a PHE.

B Fair evidence to support the recommendation that the condition be specifically considered in a PHE.

C Poor evidence regarding inclusion or exclusion of the condition in a PHE, but recommendations may be made on other grounds.

D Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

E Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

Quality of evidence was rated according to 5 levels:

I Evidence from at least 1 properly randomized controlled trial (RCT).

II-1 Evidence from well-designed controlled trials without randomization.

II-2 Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group.

II-3 Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.

III Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.

Values

The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs

Evidence on the test properties of various screening measures is summarized in the table below.

Test	Sensitivity	Specificity	Positive Predictive Value	Study Description
Pelvic exam	67%	96%	--	case series; women with pelvic masses
Ultrasound	83% 100%	94% 98%	-- 1.5% 7.7%	case series; women with pelvic masses case series; asymptomatic women >45 y (prevalence 0.09%) case series; asymptomatic women with ł 1 first degree relative with ovarian cancer (prevalence 0.39%)
TVS	100%	98%	--	case series
CA 125	93% 30%-35%	80% 95%	-- --	case-control; 3 groups (healthy, benign masses, malignant masses) blind retrospective case-control analysis of CA 125 serum samples from 2 y prior to diagnosis
Multimodal (pelvic exam, CA 125, ultrasound)	--	poorer results for pre-menopausal women 99%-100%	High in post-menopausal women --	case series; women with ovarian masses case series; post-menopausal volunteers

Effectiveness of surgical treatment was examined in 2 case series studies involving watchful waiting following surgery. There was 100% 5-year disease-free survival among patients with early stage tumours. An RCT of post-operative randomization of patients with Stage I tumours to watchful waiting or pelvic irradiation found that relapse rates depended more on degree of tumour differentiation than treatment.

An RCT found no significant difference in 5-year disease-free survival for patients with early stage cancer randomized to chemotherapy with melphalan or compared to those receiving no treatment (91% and 98%). A companion study also found no significant difference for between patients randomized to melphalan or to a single dose of intraperitoneal Chromic Phosphate (80% for both groups). Concerns exist about the toxicity of both of these agents. Evidence on radiotherapy is scarce.

A case series involving asymptomatic women with ł 1 first degree relative with ovarian cancer reported a prevalence of 3.9%, a positive predictive value of 7.7%, and higher false positive rates due to a higher incidence of benign masses.

There are no RCTs on screening for ovarian cancer. Potential adverse effects related to false positive results (e.g., patient anxiety) or false negative results (e.g., false sense of security) have not been quantified. Studies have reported a number of adverse outcomes following diagnostic laparotomy. The potential costs of screening all women over 45 are prohibitive.

Recommendations

Recommendation grade [A, B, C, D, E] and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

Fair evidence exists to exclude (from the PHE) screening of asymptomatic pre- and post-menopausal women using pelvic examination, ultrasound, TVS, CA 125 or a combination of measures [D, I, II-2, III] However, if pelvic examination is done for other purposes (e.g., pap smear), it may be prudent to examine the adnexa as well.
There is insufficient evidence to recommend for or against multimodal screening (pelvic examination, TVS, CA 125) of women with more than 1 first degree relative with ovarian cancer [C, III].

Validation

This report was externally peer reviewed. This report was externally peer-reviewed. The 1989 U.S. Preventive Services Task Force and the American College of Physicians do not recommend routine screening of asymptomatic women. The latter group recommends specialist referral of women with hereditary ovarian cancer syndrome, and decision-making based on additional risk factors for women with a family history.

Selected References

Source Document

Gladstone CQ. Screening for ovarian cancer. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 870-81.

Link to Full Text of this review

Link to Summary Table of Recommendations of this review

Link to Selected References list of this review

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A	Good evidence to support the recommendation that the condition be specifically considered in a PHE.
B	Fair evidence to support the recommendation that the condition be specifically considered in a PHE.
C	Poor evidence regarding inclusion or exclusion of the condition in a PHE, but recommendations may be made on other grounds.
D	Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.
E	Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

I	Evidence from at least 1 properly randomized controlled trial (RCT).
II-1	Evidence from well-designed controlled trials without randomization.
II-2	Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group.
II-3	Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.
III	Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.