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Ovarian Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Description of the Evidence


Other Potential Markers

Research continues to find other biomarkers that either alone or in combination with CA-125 concentrations may lead to the early detection of ovarian cancer. A panel of biomarkers that included CA-125, HE4, transthyretin, CA15.3, and CA72.4 was evaluated using specimens assembled from multiple cohort and randomized trials, including the PLCO trial.[23] The phase II and III biomarker studies concluded that CA-125 remained the "single-best biomarker" for ovarian cancer. Another retrospective study, nested within the PLCO trial and included 118 ovarian cancer cases and 8 controls per case, evaluated 7 proteomic biomarkers (apolipoprotein A1, truncated transthyretin, transferrin, hepcidin, beta-2 microglobulin, connective tissue activating protein III, and inter-alpha-trypsin inhibitor heavy-chain) in addition to CA-125.[33] The addition of the seven protein biomarkers to CA-125 did not improve the sensitivity beyond the use of CA-125 levels alone. This contrasted with this same group's preliminary evaluation of these markers using postdiagnostic rather than prediagnostic blood samples.[34]

Harms From Screening

The PLCO trial provides the most reliable data to date on screening-related harms.[26] The rate of minor complications associated with CA-125 and TVU such as bruising or fainting occurred at a rate of 58.3 cases per 10,000 women screened with CA-125 and 3.3 cases per 10,000 women screened with TVU. Major complications associated with the diagnostic procedures among women diagnosed with ovarian cancer included infections, blood loss, bowel injury, and cardiovascular events. At least one major complication was reported among 52% of women diagnosed in the usual care group and 45% among women diagnosed with ovarian cancer in the screened group.

False-positive tests occurred among 3,285 women, translating to a rate of about 5% at each screening round. The majority of false-positive tests (60%) result from TVU. Of the 3,285 women with false-positive results, 33% underwent surgery. Of the 1,080 women who underwent surgery, 15% had 222 major complications, for a rate of 20.6 complications per 100 surgical procedures.[26]

Women in the intervention group were more likely to have had an oophorectomy than those in the control group. Rates of oophorectomy were 85.7 per 10,000 person-years in the screened group compared with 64.2 per 10,000 person-years in the usual care group (rate ratio, 1.33; 95% CI, 1.24–1.43).[26]


  1. American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed March 13, 2013.
  2. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda, Md: National Cancer Institute, 2012. Also available online. Last accessed February 21, 2013.
  3. Cramer DW: The epidemiology of endometrial and ovarian cancer. Hematol Oncol Clin North Am 26 (1): 1-12, 2012.
  4. Prat J: Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch 460 (3): 237-49, 2012.
  5. Hunn J, Rodriguez GC: Ovarian cancer: etiology, risk factors, and epidemiology. Clin Obstet Gynecol 55 (1): 3-23, 2012.
  6. Smith LH, Oi RH: Detection of malignant ovarian neoplasms: a review of the literature. I. Detection of the patient at risk; clinical, radiological and cytological detection. Obstet Gynecol Surv 39 (6): 313-28, 1984.
  7. Hall DJ, Hurt WG: The adnexal mass. J Fam Pract 14 (1): 135-40, 1982.
  8. Goff BA, Mandel LS, Melancon CH, et al.: Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA 291 (22): 2705-12, 2004.
  9. Lim AW, Mesher D, Gentry-Maharaj A, et al.: Predictive value of symptoms for ovarian cancer: comparison of symptoms reported by questionnaire, interview, and general practitioner notes. J Natl Cancer Inst 104 (2): 114-24, 2012.
  10. Higgins RV, van Nagell JR Jr, Woods CH, et al.: Interobserver variation in ovarian measurements using transvaginal sonography. Gynecol Oncol 39 (1): 69-71, 1990.
  11. Sharma A, Apostolidou S, Burnell M, et al.: Risk of epithelial ovarian cancer in asymptomatic women with ultrasound-detected ovarian masses: a prospective cohort study within the UK collaborative trial of ovarian cancer screening (UKCTOCS). Ultrasound Obstet Gynecol 40 (3): 338-44, 2012.
  12. Menon U, Gentry-Maharaj A, Hallett R, et al.: Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 10 (4): 327-40, 2009.
  13. Bast RC Jr, Feeney M, Lazarus H, et al.: Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 68 (5): 1331-7, 1981.
  14. Bast RC Jr, Klug TL, St John E, et al.: A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 309 (15): 883-7, 1983.
  15. Jacobs I, Stabile I, Bridges J, et al.: Multimodal approach to screening for ovarian cancer. Lancet 1 (8580): 268-71, 1988.
  16. Buys SS, Partridge E, Greene MH, et al.: Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial. Am J Obstet Gynecol 193 (5): 1630-9, 2005.
  17. Gohagan JK, Levin DL, Prorok JC, et al., eds.: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Control Clin Trials 21(6 suppl): 249S-406S, 2000.
  18. Niloff JM, Knapp RC, Schaetzl E, et al.: CA125 antigen levels in obstetric and gynecologic patients. Obstet Gynecol 64 (5): 703-7, 1984.
  19. Haga Y, Sakamoto K, Egami H, et al.: Evaluation of serum CA125 values in healthy individuals and pregnant women. Am J Med Sci 292 (1): 25-9, 1986.
  20. Jacobs I, Bast RC Jr: The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 4 (1): 1-12, 1989.
  21. Zurawski VR Jr, Orjaseter H, Andersen A, et al.: Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer. Int J Cancer 42 (5): 677-80, 1988.
  22. Helzlsouer KJ, Bush TL, Alberg AJ, et al.: Prospective study of serum CA-125 levels as markers of ovarian cancer. JAMA 269 (9): 1123-6, 1993.
  23. Cramer DW, Bast RC Jr, Berg CD, et al.: Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 4 (3): 365-74, 2011.
  24. Jacobs I, Davies AP, Bridges J, et al.: Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. BMJ 306 (6884): 1030-4, 1993.
  25. Einhorn N, Sjövall K, Knapp RC, et al.: Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol 80 (1): 14-8, 1992.
  26. Buys SS, Partridge E, Black A, et al.: Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 305 (22): 2295-303, 2011.
  27. Partridge E, Kreimer AR, Greenlee RT, et al.: Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol 113 (4): 775-82, 2009.
  28. Kobayashi H, Yamada Y, Sado T, et al.: A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 18 (3): 414-20, 2008 May-Jun.
  29. Jacobs IJ, Skates SJ, MacDonald N, et al.: Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 353 (9160): 1207-10, 1999.
  30. Pinsky PF, Zhu C, Skates SJ, et al.: Potential effect of the risk of ovarian cancer algorithm (ROCA) on the mortality outcome of the Prostate, Lung, Colorectal and Ovarian (PLCO) trial. Int J Cancer 132 (9): 2127-33, 2013.
  31. Drescher CW, Shah C, Thorpe J, et al.: Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule. J Clin Oncol 31 (3): 387-92, 2013.
  32. Xu JL, Commins J, Partridge E, et al.: Longitudinal evaluation of CA-125 velocity and prediction of ovarian cancer. Gynecol Oncol 125 (1): 70-4, 2012.
  33. Moore LE, Pfeiffer RM, Zhang Z, et al.: Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cancer 118 (1): 91-100, 2012.
  34. Clarke CH, Yip C, Badgwell D, et al.: Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer. Gynecol Oncol 122 (3): 548-53, 2011.

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
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