Diagnostic Performance of the International Ovarian Tumor Analysis Simple Rules with CA125 in Differentiating between Benign and Malignant Adnexal Masses
Main Article Content
Abstract
Objectives: To evaluate the diagnostic performance of the International Ovarian Tumor Analysis (IOTA) simple rules in combination with serum tumor marker Cancer Antigen 125 (CA125).
Materials and Methods: This secondary analysis was based on a previous prospective diagnostic single-center study conducted at Siriraj Hospital, Thailand, between May 1, 2018, and May 31, 2019. Gynecological patients scheduled for an elective adnexal surgery at Siriraj Hospital were recruited. Preoperative ultrasound was performed within 120 days before surgery. The assessment included IOTA simple rules, IOTA simple rules with subjective assessment, and IOTA simple rules with CA125. The sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC) were assessed.
Results: A total of 357 patients from the original study cohort were included, and all were found eligible. The IOTA simple rules were applicable in 316 cases (88.5%), and achieved an AUC of 0.938 (95% CI 0.897-0.979). The IOTA simple rules along with subjective assessment demonstrated a similar AUC, 0.933 (95% CI 0.892-0.975). Integrating CA125 with the IOTA simple rules reduced the AUC to 0.825 (95% CI 0.776–0.875). When CA125 was applied exclusively to the inconclusive group, the AUC was 0.909 (95% CI 0.866–0.953). The optimal cutoff value of CA125 calculated from our cohort was 115 U/ml.
Conclusion: The IOTA simple rules are an excellent model for differentiating benign and malignant adnexal masses. Selective use of CA125 or subjective assessment in inconclusive cases can support decision-making.
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
Huang J, Chan WC, Ngai CH, Lok V, Zhang L, Lucero-Prisno DE, et al. Worldwide burden, risk factors, and temporal trends of ovarian cancer: A global study. Cancers (Basel) 2022;14:2230.
Fung-Kee-Fung M, Kennedy EB, Biagi J, Colgan T, D’Souza D, Elit LM, et al. The optimal organization of gynecologic oncology services: a systematic review. Curr Oncol 2015;22:e282-93.
Engelen MJ, Kos HE, Willemse PH, Aalders JG, de Vries EG, Schaapveld M, et al. Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma. Cancer 2006;106:589-98.
Price MA, Alvarado BE, Rosendaal NTA, Camara SMA, Pirkle CM, Velez MP. Early and surgical menopause associated with higher framingham risk scores for cardiovascular disease in the canadian longitudinal study on aging. Menopause 2021;28: 484-90.
Pillay OC, Manyonda I. The surgical menopause. Best Pract Res Clin Obstet Gynaecol 2022;81:111-8.
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.
Jivangkul C, Charoenchainont P, Leelahakorn S, Hanidhikul P, Sripramote M. Ultrasonographic scoring system for preoperative discrimination between benign and malignant ovarian tumors. Thai J Obstet Gynaecol 2002;14:231-6.
Bamniya J, Singh P, Patel D, Chaudhary A, Ladola H. Diagnostic performance of international ovarian tumor analysis-simple rules versus risk malignancy index 2 scoring system to differentiate between benign and malignant adnexal masses. Thai J Obstet Gynaecol 2021;29:331-9.
Timmerman D, Planchamp F, Bourne T, Landolfo C, du Bois A, Chiva L, et al. ESGO/ISUOG/IOTA/ESGE Consensus statement on preoperative diagnosis of ovarian tumors. Ultrasound Obstet Gynecol 2021;58:148-68.
Berek JS. Berek & Novak’s Gynecology: Wolters Kluwer; 2019.
Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res 2019;12:28.
Zhang R, Siu MKY, Ngan HYS, Chan KKL. Molecular biomarkers for the early detection of ovarian cancer. Int J Mol Sci 2022;23:12041.
Guo Y, Zhao B, Zhou S, Wen L, Liu J, Fu Y, et al. A comparison of the diagnostic performance of the O-RADS, RMI4, IOTA LR2, and IOTA SR systems by senior and junior doctors. Ultrasonography 2022;41:511-8.
Wang R, Yang Z. Evaluating the risk of malignancy in adnexal masses: validation of O-RADS and comparison with ADNEX model, SA, and RMI. Ginekol Pol 2023;94:799-806.
Koneczny J, Czekierdowski A, Florczak M, Poziemski P, Stachowicz N, Borowski D. The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses. Ginekol Pol 2017;88:647-53.
Poonyakanok V, Tanmahasamut P, Jaishuen A, Wongwananuruk T, Asumpinwong C, Panichyawat N, et al. Preoperative evaluation of the ADNEX model for the prediction of the ovarian cancer risk of adnexal masses at Siriraj Hospital. Gynecol Obstet Invest 2021;86:132-8.
Jacobs I, Bast RC, Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 1989;4:1-12.
Skates SJ, Mai P, Horick NK, Piedmonte M, Drescher CW, Isaacs C, et al. Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status. Cancer Prevention Research 2011;4:1401-8.
Hohn AK, Brambs CE, Hiller GGR, May D, Schmoeckel E, Horn LC. 2020 WHO classification of female genital tumors. Geburtshilfe Frauenheilkd 2021;81:1145-53.
Prat J, Oncology FCoG. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2014;124:1-5.
Chankrachang A, Lattiwongsakorn W, Tantipalakorn C, Tongsong T. Diagnostic performance of ADNEX model and IOTA simple rules in differentiating malignant from benign adnexal masses when assessed by non-expert examiners. J Clin Med 2025;14:1-11.
Gareeballah A, Gameraddin M, Alshoabi SA, Alsaedi A, Elzaki M, Alsharif W, et al. The diagnostic performance of international ovarian tumor analysis: Simple rules for diagnosing ovarian tumors-a systematic review and meta-analysis. Front Oncol 2024;14:1474930.
Alcazar JL, Pascual MA, Graupera B, Auba M, Errasti T, Olartecoechea B, et al. External validation of IOTA simple descriptors and simple rules for classifying adnexal masses. Ultrasound Obstet Gynecol 2016;48:397-402.
Phinyo P, Patumanond J, Saenrungmuaeng P, Chirdchim W, Pipanmekaporn T, Tantraworasin A, et al. Diagnostic added-value of serum CA-125 on the IOTA simple rules and derivation of practical combined prediction models (IOTA SR X CA-125). Diagnostics 2021;11:1-15.
Meys E, Rutten I, Kruitwagen R, Slangen B, Lambrechts S, Mertens H, et al. Simple rules, Not so simple: The use of international ovarian tumor analysis (IOTA) terminology and simple rules in inexperienced hands in a prospective multicenter cohort study. Ultraschall Med 2017;38:633-41.
Tinnangwattana D, Vichak-Ururote L, Tontivuthikul P, Charoenratana C, Lerthiranwong T, Tongsong T. IOTA simple rules in differentiating between benign and malignant adnexal masses by non-expert examiners. Asian Pac J Cancer Prev 2015;16:3835-8.