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. 2013 Oct 1;119(19):3454-61.
doi: 10.1002/cncr.28183. Epub 2013 Aug 26.

A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value

Karen H Lu  1 , Steven Skates, Mary A Hernandez, Deepak Bedi, Therese Bevers, Leroy Leeds, Richard Moore, Cornelius Granai, Steven Harris, William Newland, Olasunkanmi Adeyinka, Jeremy Geffen, Michael T Deavers, Charlotte C Sun, Nora Horick, Herbert Fritsche, Robert C Bast Jr
Affiliations

A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value

Karen H Lu et al. Cancer. .

Abstract

Background: A 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS).

Methods: A single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk).

Results: A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels.

Conclusions: ROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer.

Keywords: CA125; cancer screening; ovarian cancer screening; positive predictive value; transvaginal ultrasound.

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Conflict of interest statement

Conflicts of Interest

Steven Skates is a co-inventor of the Risk of Ovarian Cancer Algorithm, patent number US5800347, which Massachusetts General Hospital has licensed. Deepak Bedi is an unpaid consultant and an unpaid member of the speaker’s bureau for Philips Healthcare. Richard Moore has received research funding from Fujirebio Diagnostics Inc and Abbott Diagnostics Inc.

Robert C Bast Jr. receives royalties for the discovery of CA 125 from Fujirebio Diagnostics Inc and serves on the advisory board for Vermillion. None of the other authors declared any conflicts of interest.

Figures

Figure 1
Figure 1
Overall flow diagram for participants through December 1, 2011 showing the number of patients by most acute ROCA category. TVS = transvaginal ultrasound
Figure 2
Figure 2
CA125 values over time for invasive ovarian cancers. (a) Stage 1C mixed grade endometrioid and clear cell carcinoma (b) Stage IC high grade mixed mucinous and endometrioid type with clear cell carcinoma (c) Stage lA high grade serous carcinoma (d) Stage IIB high grade serous carcinoma and high grade endometrioid
See this image and copyright information in PMC

References

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