Investigating the performance and cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer (SUBSONiC-study): protocol of a prospective multicenter cohort study in the Netherlands

Evelyne M J Meys, Iris J G Rutten, Roy F P M Kruitwagen, Brigitte F Slangen, Martin G M Bergmans, Helen J M M Mertens, Ernst Nolting, Dieuwke Boskamp, Regina G H Beets-Tan, Toon van Gorp, Evelyne M J Meys, Iris J G Rutten, Roy F P M Kruitwagen, Brigitte F Slangen, Martin G M Bergmans, Helen J M M Mertens, Ernst Nolting, Dieuwke Boskamp, Regina G H Beets-Tan, Toon van Gorp

Abstract

Background: Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which improves outcome and overall survival. The Risk of Malignancy Index is currently the most commonly used method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity 75-80% and specificity 85-90%). Recent reports show that other methods, such as simple ultrasound-based rules, subjective assessment and (Diffusion Weighted) Magnetic Resonance Imaging might be superior to the RMI in the pre-operative differentiation of adnexal masses.

Methods/design: A prospective multicenter cohort study will be performed in the south of The Netherlands. A total of 270 women diagnosed with at least one pelvic mass that is suspected to be of ovarian origin who will undergo surgery, will be enrolled. We will apply the Risk of Malignancy Index with a cut-off value of 200 and a two-step triage test consisting of simple ultrasound-based rules supplemented -if necessary- with either subjective assessment by an expert sonographer or Magnetic Resonance Imaging with diffusion weighted sequences, to characterize the adnexal masses. The histological diagnosis will be the reference standard. Diagnostic performances will be expressed as sensitivity, specificity, positive and negative predictive values and likelihood ratios.

Discussion: We hypothesize that this two-step triage test, including the simple ultrasound-based rules, will have better diagnostic accuracy than the Risk of Malignancy Index and therefore will improve the management of women with adnexal masses. Furthermore, we expect this two-step test to be more cost-effective. If the hypothesis is confirmed, the results of this study could have major effects on current guidelines and implementation of the triage test in daily clinical practice could be a possibility.

Trial registration: ClinicalTrials.gov: registration number NCT02218502.

Figures

Fig. 1
Fig. 1
Schematic presentation of three different RMI score algorithms. This figure illustrates 3 different versions of the RMI score system: RMI-I [5], RMI-II [6] and RMI-III [7]. These versions differ from each other in the score attributed to the ultrasound features and menopausal status of the patient

References

    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, DM P. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. 2010.
    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29. doi: 10.3322/caac.20138.
    1. Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO. Centralisation of services for gynaecological cancer. Cochrane Database Syst Rev. 2012;3:CD007945.
    1. Weber S, McCann CK, Boruta DM, Schorge JO, Growdon WB. Laparoscopic surgical staging of early ovarian cancer. Rev Obstet Gynaecol. 2011;4:117–22.
    1. Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990;97:922–9. doi: 10.1111/j.1471-0528.1990.tb02448.x.
    1. Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, et al. Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996;103:826–31. doi: 10.1111/j.1471-0528.1996.tb09882.x.
    1. Tingulstad S, Hagen B, Skjeldestad FE, Halvorsen T, Nustad K, Onsrud M. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet Gynecol. 1999;93:448–52. doi: 10.1097/00006250-199903000-00028.
    1. Dutch guideline epithelial ovarian carcinoma. []
    1. Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008;31:681–90. doi: 10.1002/uog.5365.
    1. Timmerman D, Ameye L, Fischerova D, Epstein E, Melis GB, Guerriero S, et al. Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group. BMJ. 2010;341:c6839. doi: 10.1136/bmj.c6839.
    1. Kaijser J, Sayasneh A, Van Hoorde K, Ghaem-Maghami S, Bourne T, Timmerman D, et al. Presurgical diagnosis of adnexal tumours using mathematical models and scoring systems: a systematic review and meta-analysis. Hum Reprod Update. 2013;20:449–62. doi: 10.1093/humupd/dmt059.
    1. Valentin L. Pattern recognition of pelvic masses by gray-scale ultrasound imaging: the contribution of Doppler ultrasound. Ultrasound Obstet Gynecol. 1999;14:338–47. doi: 10.1046/j.1469-0705.1999.14050338.x.
    1. Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, et al. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer. 2012;48:1649–56. doi: 10.1016/j.ejca.2011.12.003.
    1. Valentin L, Jurkovic D, Van Calster B, Testa A, Van Holsbeke C, Bourne T, et al. Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses. Ultrasound Obstet Gynecol. 2009;34:345–54. doi: 10.1002/uog.6415.
    1. Testa A, Kaijser J, Wynants L, Fischerova D, Van Holsbeke C, Franchi D, et al. Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study. Br J Cancer. 2014;111:680–8. doi: 10.1038/bjc.2014.333.
    1. Sayasneh A, Wynants L, Preisler J, Kaijser J, Johnson S, Stalder C, et al. Multicentre external validation of IOTA prediction models and RMI by operators with varied training. Br J Cancer. 2013;108:2448–54. doi: 10.1038/bjc.2013.224.
    1. Ameye L, Timmerman D, Valentin L, Paladini D, Zhang J, Van Holsbeke C, et al. Clinically oriented three-step strategy for assessment of adnexal pathology. Ultrasound Obstet Gynecol. 2012;40:582–91. doi: 10.1002/uog.11177.
    1. Dodge JE, Covens AL, Lacchetti C, Elit LM, Le T, Devries-Aboud M, et al. Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis. Gynecol Oncol. 2012;126:157–66. doi: 10.1016/j.ygyno.2012.03.048.
    1. Qayyum A, Coakley FV, Westphalen AC, Hricak H, Okuno WT, Powell B. Role of CT and MR imaging in predicting optimal cytoreduction of newly diagnosed primary epithelial ovarian cancer. Gynecol Oncol. 2005;96:301–6. doi: 10.1016/j.ygyno.2004.06.054.
    1. EFSUMB Minimum training recommendations for the practice of medical ultrasound. Ultraschall Med. 2006;27:79–105. doi: 10.1055/s-2006-933605.
    1. WHO . World Health Organization classification of tumours. Pathology and genetics of the breast and female genital organs. 2003.
    1. Commission Quality & Occupation of the Dutch Society for Pathology, Advice retention period. []
    1. Rosner B. Fundamentals of Biostatistics. 7. Boston: Brooks/Cole; 2010.
    1. Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17:857–72. doi: 10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>;2-E.
    1. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45. doi: 10.2307/2531595.
    1. Brennan P, Silman A. Statistical methods for assessing observer variability in clinical measures. BMJ. 1992;304:1491–4. doi: 10.1136/bmj.304.6840.1491.
    1. Vergote I, De Brabanter J, Fyles A, Bertelsen K, Einhorn N, Sevelda P, et al. Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. Lancet. 2001;357:176–82. doi: 10.1016/S0140-6736(00)03590-X.

Source: PubMed

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