title: Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.
abstract: Purpose:Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design:Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history orBRCA1/2mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results:Specificity for ultrasound referral was 92% versus 90% (P= 0.0001), and PPV was 4.6% versus 10% (P> 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historicalBRCA1controls;P= 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions:For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation.Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Skates
authors.affiliation: National Cancer Institute, Rockville, Maryland.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.affiliation: Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Buys
authors.affiliation: National Cancer Institute, Rockville, Maryland.
authors.forename: Phuong L
authors.initials: PL
authors.lastname: Mai
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Powel
authors.initials: P
authors.lastname: Brown
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Marion
authors.initials: M
authors.lastname: Piedmonte
authors.affiliation: NorthShore University Health System, Evanston, Illinois.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Rodriguez
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: John O
authors.initials: JO
authors.lastname: Schorge
authors.affiliation: National Cancer Institute, Rockville, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Sherman
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.affiliation: University of South Florida, Tampa, Florida.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rutherford
authors.affiliation: University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Brewster
authors.affiliation: Ohio State University and the James Cancer Center, Columbus, Ohio.
authors.forename: David M
authors.initials: DM
authors.lastname: O'Malley
authors.affiliation: University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Edward
authors.initials: E
authors.lastname: Partridge
authors.affiliation: Rex Cancer Center, Raleigh, North Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Boggess
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Drescher
authors.affiliation: Georgetown University Medical Center, Lombardi Cancer Center, Washington, District of Columbia.
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.affiliation: Duke University Medical Center, Division of Gynecologic Oncology, Durham, North Carolina.
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.affiliation: University of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Susan
authors.initials: S
authors.lastname: Domchek
authors.affiliation: Denver Health Medical Center, Denver, Colorado.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Davidson
authors.affiliation: Magee-Womens Hospital, Pittsburgh, Pennsylvania.
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
authors.affiliation: The Iowa Clinic, Gynecologic Oncology, Des Moines, Iowa.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Elg
authors.affiliation: Dana-Farber Cancer Center in Clinical Affiliation with South Shore Hospital, South Weymouth, Massachusetts.
authors.forename: Katie
authors.initials: K
authors.lastname: Wakeley
authors.affiliation: Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
authors.affiliation: Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Armstrong
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Ira
authors.initials: I
authors.lastname: Horowitz
authors.affiliation: The University of Kansas Cancer Center, Westwood, Kansas.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Fabian
authors.affiliation: Stephenson Cancer Center, University of Oklahoma HSC, Oklahoma City, Oklahoma.
authors.forename: Joan
authors.initials: J
authors.lastname: Walker
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sluss
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: William
authors.initials: W
authors.lastname: Welch
authors.affiliation: National Cancer Institute, Rockville, Maryland.
authors.forename: Lori
authors.initials: L
authors.lastname: Minasian
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Nora K
authors.initials: NK
authors.lastname: Horick
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Carol H
authors.initials: CH
authors.lastname: Kasten
authors.affiliation: University of Florida, Gainesville, Florida.
authors.forename: Susan
authors.initials: S
authors.lastname: Nayfield
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona.
authors.forename: David
authors.initials: D
authors.lastname: Alberts
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Finkelstein
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D018394:CA-125 Antigen / Q000097:blood*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D012307:Risk Factors
chemical_list: D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins