**Screening for Ovarian Cancer**

**Screening for Ovarian Cancer**

#### Poonam Jani and Rema Iyer Poonam Jani and Rema Iyer Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.72726

#### **Abstract**

[47] Woopen H, Sehouli J. Current and future options in the treatment of malignant ascites

[48] Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. Journal of Clinical Oncology. 2014;

[49] Ferriss JS, Java JJ, Bookman MA, Fleming GF, Monk BJ, Walker JL, et al. Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: An NRG oncology/GOG study. Gynecologic

[50] El-Shami K, Elsaid A, El-Kerm Y. Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites. Journal of

[51] Zaltrap, Annex I Summary of product characteristics[internet]. Available from: http:// www.ema.europa.eu/docs/en\_GB/document\_library/EPAR\_-\_Product\_Information/

[52] Colombo N, Mangili G, Mammoliti S, Kalling M, Tholander B, Sternas L, et al. A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptom-

[53] Gotlieb WH, Amant F, Advani S, Goswami C, Hirte H, Provencher D, et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: A phase 2, randomised, double-blind, placebo-controlled

[54] Davies B, Brown PD, East N, Crimmin MJ, Balkwill FR. A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human

[55] Valle M, Federici O, Garofalo A. Patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, and role of laparoscopy in diagnosis, staging, and treatment. Surgical Oncology Clinics of North America. 2012;**21**(4):515-531. DOI:

[56] Pockros PJ, Esrason KT, Nguyen C, Duque J, Woods S. Mobilization of malignant ascites with diuretics is dependent on ascitic fluid characteristics. Gastroenterology. 1992;

[57] Latifi A, Luwor RB, Bilandzic M, Nazaretian S, Stenvers K, Pyman J, et al. Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: Molecular

[58] Kobal B, Jerman KG, Karo J, Verdenik I, Cerne K. (forthcoming 2016).Relationship of ovarian cancer tumour markers concentration between local fluid and serum: Comparison of malignant to benign condition. European Journal of Gynaecological Oncology. 2017

phenotype of chemoresistant ovarian tumors. PLoS One. 2012;**7**(10):e46858

in ovarian cancer. Anticancer Research. 2009;**29**(8):3353-3359

Oncology. 2015;**139**(1):17-22. DOI: 10.1016/j.ygyno.2015.07.103

human/002532/WC500139484.pdf [Accessed: April 12, 2017]

atic malignant ascites. Gynecologic Oncology. 2012;**125**(1):42-47

ovarian carcinoma xenografts. Cancer Research. 1993;**53**(9):2087-2091

study. The Lancet Oncology. 2012;**13**(2):154-162

10.1016/j.soc.2012.07.005

**103**:1302-1306

**32**(13):1302-1308. DOI: 10.1200/JCO.2013.51.4489

Clinical Oncology. 2007;**25**(18):9043

214 Ovarian Cancer - From Pathogenesis to Treatment

Ovarian cancer is often diagnosed at an advanced stage and is associated with poor survival. Screening aims at detection of early stage disease with a view of improving overall survival. Incidence of ovarian cancer is about 1–2% in the low-risk and 10–40% in the high-risk population. Transvaginal ultrasound (TVS) and serum CA125 levels have been used for early detection. Annual screening with TVS and serum CA125 levels (using a cutoff value) has not demonstrated detection of ovarian cancer at an early stage. Multimodal screening (MMS) using sequential CA125 levels (with interpretation of risk using Risk of Ovarian Cancer Algorithm—ROCA) and ultrasound as the second-line test have been shown to have improved sensitivity when compared to annual ultrasound in the detection of ovarian cancer. However, no impact on survival has been demonstrated, and therefore, screening cannot be recommended in the general or high-risk population. There is evidence now to suggest that high-grade serous cancers originate from the fallopian tube where precursor lesions have been identified. Newer screening strategies are likely to shift the focus to detecting these precursor lesions with novel techniques such as exfoliative cytology, circulating tumour DNA and use of microbubbles in ultrasound imaging.

DOI: 10.5772/intechopen.72726

**Keywords:** screening, transvaginal ultrasound, CA125, ovarian cancer, multimodal screening

#### **1. Introduction**

Ovarian cancer is the seventh most common cancer in women worldwide, accounting for 4% of cancers in women. Incidence of ovarian cancer is increasing, especially in Europe and Northern America, being the fifth most common cancer in European women [1]. Even though the life time risk of developing ovarian cancer is 1–2% in the general population, since it is often diagnosed at a later stage, ovarian cancer has the highest mortality rate associated with gynaecological cancers in the developed world [2]. Therefore, there is a need to introduce a screening programme for early detection of this disease.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

Screening for any disease is aimed at detection of premalignant conditions or early stage disease. Cervical cancer screening is a successful programme as the progression from premalignant to malignant disease is well understood. However, until recently, precursor lesions were not recognised for ovarian cancer. Now, there is evidence to suggest that some of the high-grade serous cancers start as premalignant lesions in the fimbrial end of the fallopian tube as serous tubal intraepithelial carcinoma (STIC) [3]. Strategies to detect these premalignant lesions are likely to change the approach to ovarian cancer screening.

previous hysterectomy, unilateral oophorectomy, tubal ligation, increasing age and obesity. Interestingly, factors that increased visualisation of the ovaries included a history of infertility

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One of the biggest challenges in ovarian screening lies in differentiating between benign and malignant macroscopic changes. Ovarian morphology varies greatly from patient to patient, and thus benign lesions can give rise to false positive results, leading to unnecessary interventions. Unilocular cysts and those with simple septations are often benign and self-resolving. Features increasing the risk of malignancy include identification of neo-angiogenesis, multiple loculations, presence of papillary structures and solid foci [7–9]. False positives can be reduced with serial ultrasonography [10] as many ovarian lesions resolve without intervention. Benign lesions such as cysts and non-malignant solid lesions are also prevalent in the older population. In a study involving histological and ultrasound characterisation of ovarian cysts from autopsy material from 52 postmenopausal women who had died from causes other than gynaecological cancers, 56% were found to have histologically benign ovarian masses. This evidence suggests that many women will have benign lesions and so ultrasound testing could potentiate unnecessary over-investigating and surgical interventions [11]. The malignant potential of inclusion cysts are yet to be determined, however, it has been proven that TVS is a valid system for detecting malignancy after initial assessment at 1 year. In a study assessing the malignant potential of inclusion cysts, of the 1234 patients carrying ovarian inclusion cysts and 22,914 patients with normal ovaries, 432 women were diagnosed with ovarian cancer, respectively. Overall, the

study showed the wider potential of application of TVS as a screening modality [12].

A well-defined criteria or reliable method of quantification needs to be introduced in order to differentiate between benign and malignant cysts. The University of Kentucky has developed a morphological index (MI) score looking at ovarian volume and macroscopic features. In their study, malignancy correlated to an increase in MI score with serial imaging, whereas benign tumours correlated to a decreased or stable MI score [13]. There is scope, therefore, for more accurate quantification of malignant potential, using risk predictors and TVS-led assessment. New strategies to aid in accurate detection of malignant tumours include neuronal networks and pattern recognition models [14]. These developments are still in their infancy; however, a multicentre study demonstrated that borderline tumours, struma ovarii, papillary cystadenofibromas and myomas proved most difficult to reliably differentiate using ultrasound even

Magnetic resonance imaging (MRI) is a further imaging modality to consider for screening, due to its detailed visualisation of the pelvis. As an option for screening, however, implications of cost, duration of test, contra-indications for the wider population including place-

Tumour markers are substances, mostly proteins produced by the tumour cells, which can be detected in the blood and other bodily secretions of the affected individual. These markers

and increasing age at menopause [6].

with logistic regression models [15].

**3. Tumour markers**

ment of metal work, all pose great hurdles to acceptability.
