Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule

Abstract

Purpose: To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention.

Patients and methods: Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated ≥ 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries.

Results: Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have ≥ stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC.

Conclusion: These results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection.

Fig 1.

Flow of participants through study. All percentages refer to proportion of population defined in preceding row. UK FOCSS, United Kingdom Familial Ovarian Cancer Screening Study; FTC, fallopian tube cancer; OC, ovarian cancer; PPC, primary peritoneal cancer; RRSO, risk-reducing salpingo-oophorectomy. (*) Ineligible on basis of new information regarding diagnoses in family history becoming available subsequent to recruitment. (†)Lost to follow-up: unable to establish current whereabouts; nonresponders: failed to respond despite confirmation of correct contact details. (‡) Reason for surgery pending, but known not to have had OC, FTC, or PPC.

Fig A1.

Annual transvaginal ultrasound scan (TVS) and CA125 screening. Normal, equivocal, and abnormal scan definitions provided in Appendix. Elevated CA125: ≥ 35 and > 30 IU/mL in premenopausal and postmenopausal women, respectively. (*) Earlier intervention if clinical suspicion warrants. These represent guidelines only; clinical management of the women remained at the discretion of collaborating local gynecologists. When an elevated CA125 or non-normal scan was found at an annual screen, it was the local gynecologist's decision whether the test should be repeated before surgical investigation. If the test was repeated, the interval before repeat testing was also at his or her discretion. The study guidelines recommended that intervention be considered earlier if there was clinical suspicion of cancer to discourage unnecessary delays when screening test results were clearly concerning.