Abstract
PurposeTo establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC).Patients and MethodsWomen whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO.ResultsBetween June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09).ConclusionROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women.
Highlights
Inherited mutations in BRCA1 and BRCA2 and Lynch syndrome (LS) account for a significant minority (15% to 25%) of ovarian cancers (OCs)[1,2] and confer a high risk for OC: 11% to 37% by age 70 years in BRCA2 carriers and 39% to 65% in BRCA1 carriers.[3,4] Other lower-penetrance homologous repair pathway genes have been implicated in familial OC.[5,6] medium-term survival with BRCAassociated OC exceeds that of sporadic OC,[7,8] the long-term outlook remains poor.[9]
To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC)
Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at Risk-reducing salpingooophorectomy (RRSO))
Summary
Medium-term survival with BRCAassociated OC exceeds that of sporadic OC,[7,8] the long-term outlook remains poor.[9] Risk-reducing salpingo-oophorectomy (RRSO) for women older than 35 years of age to prevent OC or fallopian tube cancer (FTC) and to detect occult neoplasia is recommended as the only proven mortalityreducing intervention.[10,11] effective when used premenopausally,[10,11] RRSO causes infertility and premature menopause, with associated cardiovascular risks,[12] osteoporosis,[13] and neurologic risks[14] ( premature menopause can be treated with hormone replacement therapy). Some women decline RRSO regardless of OC risk, and others prefer to defer it (eg, until menopause). Effective OC screening would be a welcome option for such women
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