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

Diane Stirling, D Gareth R Evans, Gabriella Pichert, Andrew Shenton, Elaine N Kirk, Sylvia Rimmer, C Michael Steel, Sheila Lawson, R M Camille Busby-Earle, Jane Walker, Fiona I Lalloo, Diana M Eccles, Anneke M Lucassen, Mary E Porteous
Journal of Clinical Oncology 2005 August 20, 23 (24): 5588-96

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: 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.

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