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. 2017 Jul 15;23(14):3628-3637.
doi: 10.1158/1078-0432.CCR-15-2750. Epub 2017 Jan 31.

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

Steven J Skates  1 , Mark H Greene  2 , Saundra S Buys  3 , Phuong L Mai  2 , Powel Brown  4 , Marion Piedmonte  5 , Gustavo Rodriguez  6 , John O Schorge  1 , Mark Sherman  2 , Mary B Daly  7 , Thomas Rutherford  8 , Wendy R Brewster  9 , David M O'Malley  10 , Edward Partridge  11 , John Boggess  12 , Charles W Drescher  13 , Claudine Isaacs  14 , Andrew Berchuck  15 , Susan Domchek  16 , Susan A Davidson  17 , Robert Edwards  18 , Steven A Elg  19 , Katie Wakeley  20 , Kelly-Anne Phillips  21   22   23 , Deborah Armstrong  24 , Ira Horowitz  25 , Carol J Fabian  26 , Joan Walker  27 , Patrick M Sluss  1 , William Welch  28 , Lori Minasian  2 , Nora K Horick  1 , Carol H Kasten  29 , Susan Nayfield  30 , David Alberts  31 , Dianne M Finkelstein  1 , Karen H Lu  4
Affiliations

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

Steven J Skates et al. Clin Cancer Res. .

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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Conflict of interest statement

Conflicts of Interest: Steven Skates is a co-developer of the risk of ovarian cancer algorithm. Massachusetts General Hospital has licensed software implementing the algorithm.

Figures

Figure 1
Figure 1
Early detection of ovarian cancer via ROCA even though CA125 remains below 35 U/mL. The consistent increase in CA125 from the nadir (blue arrow) increases the calculated risk of having ovarian cancer with each additional CA125 test until the risk is elevated (red circles) with a recommendation of a trans-vaginal ultrasound. Surgery was recommended at the second ultrasound and a mixed endometrioid and serous ovarian cancer (stage IIB) detected.
See this image and copyright information in PMC

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Supplementary concepts