Screening for familial ovarian cancer: failure of current protocols to detect ovarian cancer at an early stage according to the international Federation of gynecology and obstetrics system.
OBJECTIVE
To assess the effectiveness of annual ovarian cancer screening (transvaginal ultrasound and serum CA-125 estimation) in detecting presymptomatic ovarian cancer in women at increased genetic risk.


METHODS
A cohort of 1,110 women at increased risk of ovarian cancer were screened between January 1991 and March 2004; 553 were moderate-risk individuals (4% to 10% lifetime risk) and 557 were high-risk individuals (> 10% lifetime risk). Outcome measurements include the number and stage of screen-detected cancers, the number and stage of cancers not detected at screening, the number of equivocal screening results requiring recall/repetition, and the number of women undergoing surgery for benign disease.


RESULTS
Thirteen epithelial ovarian malignancies (12 invasive and one borderline), developed in the cohort. Ten tumors were detected at screening: three International Federation of Gynecology and Obstetrics (FIGO) stage I (including borderline), two stage II, four stage III, and one stage IV. Of the three cancers not detected by screening, two were stage III and one was stage IV; 29 women underwent diagnostic surgery but were found not to have ovarian cancer.


CONCLUSIONS
Annual surveillance by transvaginal ultrasound scanning and serum CA-125 measurement in women at increased familial risk of ovarian cancer is ineffective in detecting tumors at a sufficiently early stage to influence prognosis. With a positive predictive value of 17% and a sensitivity of less than 50%, the performance of ultrasound does not satisfy the WHO screening standards. In addition, the combined protocol has a particularly high false-positive rate in premenopausal women, leading to unnecessary surgical intervention.
Stirling
Diane
D
Macmillan Nurse Specialist in Genetics, Southeast of Scotland Clinical Genetic Services, Western General Hospital, Crewe Rd, Edinburgh, EH4 2XU Scotland. diane.stirling@luht.scot.nhs.uk
Evans
D Gareth R
DG
Pichert
Gabriella
G
Shenton
Andrew
A
Kirk
Elaine N
EN
Rimmer
Sylvia
S
Steel
C Michael
CM
Lawson
Sheila
S
Busby-Earle
R M Camille
RM
Walker
Jane
J
Lalloo
Fiona I
FI
Eccles
Diana M
DM
Lucassen
Anneke M
AM
Porteous
Mary E
ME
D000328:Adult; D018394:CA-125 Antigen / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008403:Mass Screening / Q000592:standards*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging* / Q000235:genetics; D018570:Risk Assessment; D014463:Ultrasonography
D018394:CA-125 Antigen