Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses

BMC Cancer

Denise da Rocha Pitta²  Luis Otávio Sarian²  Amilcar Barreta³  Elisabete Aparecida Campos²  Liliana Lucci de Angelo Andrade¹  Ana Maria Dias Fachini³  Leonardo Martins Campbell³  Sophie Derchain² 

[1] Department of Pathology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, SP 13083-970, Brazil

[2] Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas – Unicamp, Campinas, SP 13083-970, Brazil

[3] Post Graduating Program in Gynecology, Unicamp, Campinas, Brazil

关键词: Prediction of malignancy;    ROMA;    HE4;    CA125;    Ovarian tumors;    Specific symptoms;   

Others  :  1079567
DOI  :  10.1186/1471-2407-13-423

 received in 2012-11-02, accepted in 2013-09-12,  发布年份 2013

【 摘 要 】

Background

This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound.

Methods

This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae.

Results

Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI.

Conclusion

Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.

【 授权许可】

   
2013 Pitta et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61(2):69-90. Epub 2011 Feb 4. Erratum in: CA Cancer J Clin 2011, 61(2):134
• [2]INCA- Instituto Nacional de Câncer: Estimativa. 2012. http://www.inca.gov.br/estimativa/2012/ webcite [Accessed 10 October 2011]; http://www.inca.gov.br/estimativa/2012/ webcite
• [3]Vernooij F, Heintz AP, Coebergh JW, Massuger LF, Witteveen PO, van der Graaf Y: Specialized and high-volume care leads to better outcomes of ovarian cancer treatment in the Netherlands. Gynecol Oncol 2009, 112(3):455-461.
• [4]Geomini P, Kruitwagen R, Bremer GL, Cnossen J, Mol BW: The accuracy of risk scores in predicting ovarian malignancy: a systematic review. Obstet Gynecol 2009, 113(2 Pt 1):384-394.
• [5]Kaijser J, Bourne T, Valentin L, Sayasneh A, Van-Holsbeke C, Vergote I, Testa AC, Franchi D, Van-Calster B, Timmerman D: Improving strategies for diagnosing ovarian cancer: a summary of the International Ovarian Tumor Analysis (IOTA) studies. Ultrasound Obstet Gynecol 2013, 41(1):9-20.
• [6]Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van-Holsbeke C, Paladini D, Van-Calster B, Vergote I, Van-Huffel S, Valentin L: Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 2008, 31:681-690.
• [7]Hartman CA, Juliato CR, Sarian LO, Toledo MC, Jales RM, Morais SS, Pitta DR, Marussi EF, Derchain S: Ultrasound criteria and CA-125 as predictive variables of ovarian cancer in women with adnexal tumors. Ultrasound Obstet Gynecol 2012, 40(3):360-366.
• [8]Vine MF, Calingaert B, Berchuck A, Schildkraut JM: Characterization of prediagnostic symptoms among primary epithelial ovarian cancer cases and controls. Gynecol Oncol 2003, 90(1):75-82.
• [9]Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, Patras J, Mahony BS, Andersen MR: Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer 2007, 109:221-227.
• [10]Bankhead CR, Kehoe ST, Austoker J: Symptoms associated with diagnosis of ovarian cancer: a systematic review. BJOG 2005, 112(7):857-865.
• [11]Goff BA: Symptoms associated with ovarian cancer. Clin Obstet Gynecol 2012, 55(1):36-42.
• [12]Van-Calster B, Timmerman D, Bourne T, Testa AC, Van-Holsbeke C, Domali E, Jurkovic D, Neven P, Van-Huffel S, Valentin L: Discrimination between benign and malignant adnexal masses by specialist ultrasound examination versus serum CA-125. J Natl Cancer Inst 2007, 99(22):1706-1714.
• [13]Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Dresher CW, Paley P, Urban N: Combining a symptoms index with CA125 to improve detection of ovarian cancer. Cancer 2008, 113:484-489.
• [14]Li F, Tie R, Chang K, Wang F, Deng S, Lu W, Yu L, Chen M: Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and CA125 in predicting epithelial ovarian cancer: a meta-analysis. BMC Cancer 2012, 12(1):258. BioMed Central Full Text
• [15]Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller MC, Allard WJ, Kurman RJ, Bast RC, Skates SJ: Comparison of a novel multiple marker assay vs the risk of malignancy index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol 2010, 203(3):228. e1–6
• [16]Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Drescher CW, Paley P, Urban N: Use of a symptom index, CA125 and HE4 to predict ovarian cancer. Gynecol Oncol 2010, 116(3):378-391.
• [17]Tavassoli FA, Deville P: Pathology and genetics of tumors of the breast and female genital organs. WHO Classification of tumors. Lyon: IARC Press; 2003.
• [18]Development Core Team R: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2011. URL http://www.R-project.org/ webcite
• [19]Olson SH, Mignone L, Nakraseive C, Caputo TA, Barakat RR, Harlap S: Symptoms of ovarian cancer. Obstet Gynecol 2001, 98:212-217.
• [20]Bankhead CR, Collins C, Stokes-Lampard H, Rose P, Wilson S, Clements A, Mant D, Kehoe ST, Austoker J: Identifying symptoms of ovarian cancer: a qualitative and quantitative study. BJOG 2008, 115(8):1008-1014.
• [21]Ward JH: Hierarchical grouping to optimize an objective function. J Am Stat Assoc 1963, 58:236-244.
• [22]DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988, 44:837-845.
• [23]Goff BA, Mandel L, Muntz HG, Melancon CH: Ovarian carcinoma diagnosis. Cancer 2000, 89(10):2068-2075.
• [24]Hippisley-Cox J, Coupland C: Symptoms and risk factors to identify women with suspected cancer in primary care: derivation and validation of an algorithm. Br J Gen Pract 2013, 63(606):11-21.
• [25]Van-Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, Timmerman D, De-Moor B, Vergote I: HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the risk of ovarian malignancy algorithm. Br J Cancer 2011, 5:863-870.
• [26]Rossing MA, Wicklund KG, Cushing-Haugen KL, Weiss NS: Predictive value of symptoms for early detection of ovarian cancer. J Natl Cancer Inst 2010, 102:222-229.
• [27]Goff BA, Mandel LS, Melancon CH, Muntz HG: Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA 2004, 291(22):2705-2712.
• [28]Kurman RJ, Shih IM: Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Hum Pathol 2011, 42(7):918-931.
• [29]Brown PO, Palmer C: The preclinical natural history of serous ovarian cancer: defining the target for early detection. PLoS Med 2009, 6(7):e1000114.
• [30]Gilbert L, Basso O, Sampalis J, Karp I, Martins C, Feng J, Piedimonte S, Quintal L, Ramanakumar AV, Takefman J, Grigorie MS, Artho G, Krishnamurthy S, DOvEStudy Group: Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol 2012, 13(3):285-291.
• [31]Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, Setälä M, Härkki P, Jalkanen J, Fraser J, Mäkinen J, Auranen A, Poutanen M, Perheentupa A: Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer 2009, 100:1-5.
• [32]Chapron C, Santulli P, De-Ziegler D, Noel JC, Anaf V, Streuli I, Foulot H, Souza C, Borghese B: Ovarian endometrioma: severe pelvic pain is associated with deeply infiltrating endometriosis. Hum Reprod 2012, 27:702-711.