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Supplementary Materials from 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

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posted on 2023-03-31, 20:02 authored by Steven J. Skates, Mark H. Greene, Saundra S. Buys, Phuong L. Mai, Powel Brown, Marion Piedmonte, Gustavo Rodriguez, John O. Schorge, Mark Sherman, Mary B. Daly, Thomas Rutherford, Wendy R. Brewster, David M. O'Malley, Edward Partridge, John Boggess, Charles W. Drescher, Claudine Isaacs, Andrew Berchuck, Susan Domchek, Susan A. Davidson, Robert Edwards, Steven A. Elg, Katie Wakeley, Kelly-Anne Phillips, Deborah Armstrong, Ira Horowitz, Carol J. Fabian, Joan Walker, Patrick M. Sluss, William Welch, Lori Minasian, Nora K. Horick, Carol H. Kasten, Susan Nayfield, David Alberts, Dianne M. Finkelstein, Karen H. Lu

Supplementary Materials describing "Inclusion and Exclusion Criteria" for the two studies, a detailed description of the "ROCA methods", "Sample Handling and CA125 Assay Instrumentation", and derivation of standards for "Specificity and Positive Predictive Values" for a cohort of women at increased risk.

Funding

NCI

Gynecologic Oncology Group's

Gynecologic Oncology Group

National Cancer Institute

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GOG

CCOP

National Breast Cancer Foundation

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ARTICLE 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 or BRCA1/2 mutations, 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% historical BRCA1 controls; 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.

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    Clinical Cancer Research

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    Keywords

    Cancer InterceptionBiomarkers and interventionCancer surveillance and screeningCancer PreventionEarly DetectionGynecological CancersOvarian cancer

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