The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer


      Epithelial ovarian cancer kills more women than all other gynecologic malignancies combined because of our inability to detect early-stage disease. Ultrasonography has demonstrated usefulness in the detection of ovarian cancer in asymptomatic women, but its value for the detection of early-stage epithelial ovarian cancer in women of increased risk is uncertain. We examined the usefulness of sonography in the detection of early-stage epithelial ovarian cancer in asymptomatic high-risk women who participated in the National Ovarian Cancer Early Detection Program.

      Study design

      Only asymptomatic women of increased risk for the development of ovarian cancer with initial normal gynecologic and ultrasound examinations were eligible to participate in the institutional review board–approved National Ovarian Cancer Early Detection Program. Participants underwent comprehensive gynecologic and ultrasound examinations every 6 months. Increased risk includes women with at least 1 affected first-degree relative with ovarian cancer; a personal history of breast, ovarian, or colon cancer; ≥1 affected first- and second-degree relatives with breast and or ovarian cancer; inheritance of a breast cancer mutation from an affected family member, or membership within a recognized cancer syndrome.


      The average age of the 4526 women who were evaluated was 46 years; 2610 women were premenopausal, and 1916 women were postmenopausal. A total of 12,709 scans have been performed since 1990. Visualization of both ovaries was noted in 98% of premenopausal and in 94% of postmenopausal women. Fourteen women had undergone unilateral salpingo-oophorectomy. Recall rates at less than the routine 6-month interval were 0.4% in the premenopausal and 0.3% in postmenopausal women. A total of 98 women with persistent adnexal masses were identified, and 49 invasive surgical procedures were performed that diagnosed 37 benign ovarian tumors and 12 gynecologic malignancies. All cancers were detected in asymptomatic women who had normal ultrasound and physical examinations 12 and 6 months before the cancer diagnosis. The detected malignancies were fallopian tube carcinoma (stage IIIC; n = 4 women), primary peritoneal carcinoma (n = 4 women; stage IIIA, 1 woman; stage IIIB, 2 women; stage IIIC, 1 woman), epithelial ovarian cancer (stages IIIA and IIIB; n = 2 women), and endometrial adenocarcinoma (stage IA; n = 2 women). Additionally 37 primary and 12 recurrent breast carcinomas were detected by physical examination. A total of 184 women with genetic predisposition (breast cancer positive) have undergone a prophylactic bilateral salpingo-oophorectomy; 23% of these procedures found atypical hyperplasia, and unexpectedly, 2 women (1%) were found to have stage III (A and B) primary peritoneal carcinoma.


      This study demonstrates the limited value of diagnostic ultrasound examination as an independent modality for the detection of early-stage epithelial ovarian cancer in asymptomatic women who are at increased risk for disease.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jemal A.
        • Murray T.
        • Samuels A.
        • Ghafoor A.
        • Ward E.
        • Thun M.J.
        • et al.
        Cancer statistics, 2003.
        CA Cancer J Clin. 2003; 53: 5-26
        • Yancik R.
        Ovarian cancer. age contrasts in incidence, histology, disease stage at diagnosis, and mortality.
        Cancer. 1993; 71: 517-523
        • Cohen L.S.
        • Escobar P.F.
        • Scharm C.
        • Glimco B.
        • Fishman D.A.
        Three-dimensional power Doppler improves the diagnostic accuracy for ovarian cancer prediction.
        Gynecol Oncol. 2001; 82: 40-48
        • Bourne T.H.
        • Campbell S.
        • Reynolds K.M.
        • Whitehead M.I.
        • Hampson J.
        • Royston P.
        • et al.
        Screening for early familial ovarian cancer with transvaginal ultrasonography and color blood low imaging.
        BMJ. 1993; 306: 1025-1029
        • Bell R.
        • Petticrew M.
        • Sheldon T.
        The performance of screening tests for ovarian cancer: results of a systematic review.
        BJOG. 1998; 105: 1136-1147
        • Karlan B.Y.
        • Baldwin R.L.
        • Lopez-Luevanos E.
        • Raffel L.J.
        • Barbuto D.
        • Narod S.
        • et al.
        Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: implications for ovarian cancer screening.
        Am J Obstet Gynecol. 1999; 180: 917-928
        • Liede A.
        • Karlan B.Y.
        • Baldwin R.L.
        • Platt L.D.
        • Kuperstein G.
        • Narod S.A.
        Cancer incidence in a population of Jewish women at risk for ovarian cancer.
        J Clin Oncol. 2002; 20: 1570-1577
        • van Nagell Jr., J.R.
        • DePriest P.D.
        • Reedy M.B.
        • Gallion H.H.
        • Ueland F.R.
        • Pavlik E.J.
        • et al.
        The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer.
        Gynecol Oncol. 2000; 77: 350-356
        • Fishman D.
        • Cohen L.
        Is transvaginal ultrasound effective for screening asymptomatic women for the detection of early stage epithelial ovarian carcinoma?.
        Gynecol Oncol. 2000; 77: 347-349
        • Jacobs I.J.
        • Skates S.J.
        • MacDonald N.
        • Menon U.
        • Rosenthal A.N.
        • Davies A.P.
        • et al.
        Screening for ovarian cancer: a pilot randomised controlled trial.
        Lancet. 1999; 353: 1207-1210
        • Jacobs I.
        • Stabile I.
        • Bridges J.
        • Kemsley P.
        • Reynolds C.
        • Grudzinskas J.
        • et al.
        Multimodal approach to screening for ovarian cancer.
        Lancet. 1988; 1: 268-271
        • Jacobs I.
        • Davies A.P.
        • Bridges J.
        • Stabile I.
        • Fay T.
        • Lower A.
        • et al.
        Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.
        BMJ. 1993; 306: 1030-1033
        • Einhorn N.
        • Sjovall K.
        • Knapp R.C.
        • Hall P.
        • Scully R.E.
        • Bast Jr., R.C.
        • et al.
        Prospective evaluation of serum CA125 levels for early detection of ovarian cancer.
        Obstet Gynecol. 1992; 80: 14-18
        • Campbell S.
        • Bhan V.
        • Royston P.
        • Whitehead M.I.
        • Collins W.P.
        Transabdominal screening for early ovarian cancer.
        BMJ. 1989; 299: 1363-1367
        • Kinkel K.
        • Hricak H.
        • Lu Y.
        • Kyo T.
        • Filly R.A.
        US characterization of ovarian masses: a meta-analysis.
        Radiology. 2000; 217: 803-811
        • Kurjak A.
        • Zalud I.
        • Alfirevic Z.
        Evaluation of adnexal masses with transvaginal color ultrasound.
        J Ultrasound Med. 1991; 10: 295-297
        • Fleischer A.
        • Jones III, H.
        Color Doppler sonography of ovarian masses: the importance of a multiparameter approach.
        Gynecol Oncol. 1993; 50 ([editorial]): 1-2
        • Karlan B.Y.
        • Platt L.D.
        The current status of ultrasound and color Doppler in imaging in screening for ovarian cancer.
        Gynecol Oncol. 1994; 55: S28-S33
        • Consensus Development Panel
        Ovarian cancer.
        JAMA. 1995; 273: 491-497
        • Tailor A.
        • Jurkovic D.
        • Bourne T.
        Sonographic prediction of malignancy in adnexal masses using multivariate logistic regression analysis.
        Ultrasound Obstet Gynecol. 1997; 10: 41-47
        • Timmerman D.
        • Bourne T.H.
        • Tailor A.
        • Collins W.P.
        • Verrelst H.
        • Vandenberghe K.
        • et al.
        A comparison of methods for preoperative discrimination between malignant and benign masses: the development of a new logistic regression model.
        Am J Obstet Gynecol. 1999; 181: 57-65
        • Schelling M.
        • Braun M.
        • Kuhn W.
        • Bogner G.
        • Gruber R.
        • Gnirs J.
        • et al.
        Combined transvaginal B-mode and color Doppler sonography for differential diagnosis of ovarian tumors: results of a multivariate logistic regression analysis.
        Gynecol Oncol. 2000; 77: 78-86
        • Alcazar J.
        • Jurado M.
        Prospective evaluation of a logistic model based on sonographic morphologic and color Doppler findings developed to predict adnexal malignancy.
        J Ultrasound Med. 1999; 18: 837-842
        • Aslam N.
        • Banerjee S.
        • Carr J.V.
        • Savvas M.
        • Hooper R.
        • Jurkovic D.
        Prospective evaluation of logistic regression models for the diagnosis of ovarian cancer.
        Obstet Gynecol. 2000; 96: 75-80
        • Valentin L.
        • Hagen B.
        • Tingulstad S.
        • Eik-Nes S.
        Comparison of `pattern recognition' and logistic regression models for discrimination between benign pelvic masses: a prospective cross-validation.
        Ultrasound Obstet Gynecol. 2001; 18: 357-365
        • Guerriero S.
        • Ajossa S.
        • Risalvato A.
        • Lai M.P.
        • Mais V.
        • Angiolucci M.
        • et al.
        Diagnosis of adnexal malignancies by using color Doppler energy imaging as a secondary test in persistent masses.
        Ultrasound Obstet Gynecol. 1998; 11: 277-282
        • Kurjak A.
        • Kupesic S.
        • Breyer B.
        The assessment of ovarian tumor angiogenesis: What does three-dimensional power Doppler add?.
        Ultrasound Obstet Gynecol. 1998; 12: 136-146
        • Kurjak A.
        • Kupesic S.
        • Tomislav A.
        • Kosuta D.
        Three-dimensional ultrasound and power Doppler improve the diagnosis of ovarian lesions.
        Gynecol Oncol. 2000; 76: 28-32
        • Guerriero S.
        • Alcazar J.L.
        • Ajossa S.
        • Lai M.P.
        • Errasti T.
        • Mallarini G.
        • et al.
        Comparison of conventional color and power Doppler imaging for the diagnosis of ovarian cancer: results of a European study.
        Gynecol Oncol. 2001; 83: 299-304
        • Guerriero S.
        • Alcazar J.L.
        • Coccia M.E.
        • Ajossa S.
        • Scarselli G.
        • Boi M.
        • et al.
        Complex pelvic mass as a target of evaluation of vessel distribution by color Doppler sonography for the diagnosis of adnexal malignancies: results of a Multicenter European study.
        J Ultrasound Med. 2002; 21: 1105-1111
        • Fishman D.A.
        • Singh D.
        • Lurain J.R.
        • Bozorgi K.
        The scientific basis for the early detection of early stage epithelial ovarian carcinoma: part 1.
        The Female Patient. 2002; 27: 11-15
        • Fishman D.A.
        • Singh D.
        • Lurain J.R.
        • Bozorgi K.
        The scientific basis for the early detection of early stage epithelial ovarian carcinoma: part 2, the future of early detection.
        The Female Patient. 2002; 27: 21-27
        • Baron A.T.
        • Cora E.M.
        • Lafky J.M.
        • Boardman C.H.
        • Buenafe M.C.
        • Rademaker A.
        • et al.
        Soluble epidermal growth factor receptor (sEGFR/sErbB1) as a potential risk, screening, and diagnostic serum biomarker of epithelial ovarian cancer.
        Cancer Epi Bio Prev. 2003; 12: 103-113
        • Baron A.T.
        • Cora E.M.
        • Lafky J.M.
        • Boardman C.H.
        • Buenafe M.C.
        • Rademaker A.
        • et al.
        Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer.
        Cancer Epi Bio Prev. 1999; 8: 129-137
        • Mills G.B.
        • Eder A.
        • Fang X.
        • Hasegawa Y.
        • Mao M.
        • Lu Y.
        • et al.
        Critical role of lysophospholipids in the pathophysiology, diagnosis, and management of ovarian cancer.
        Cancer Treat Res. 2002; 107: 259-283
        • Tanyi J.L.
        • Morris A.J.
        • Wolf J.K.
        • Bast R.C.
        • Lu K.
        • Smith D.
        • et al.
        Role of decreased levels of LPP-1 in accumulation of lysophosphatidic acid (LPA) in ovarian cancer.
        Clin Cancer Res. 2003; 9: 3534-3545
        • Petricoin III, E.F.
        • Ardekani A.
        • Hitt B.A.
        • Levine P.J.
        • Fusaro V.A.
        • Steinberg S.M.
        • et al.
        Serum proteomic patterns discovered using an “artificial intelligence”–based algorithm reveal disease-associated signatures of ovarian and prostate cancer.
        Lancet. 2002; 359: 572-577
      1. Conrads TP, Fusaro VA, Ross S, Hitt BA, Chen TH, Levine PJ, et al. Multiple high-resolution serum proteomic patterns for ovarian cancer detection. Enocrine-Related Cancer 2004;11:163-78.