Detection of Ovarian Cancer: The Benefits of CA125, Ultrasound or Both

Abstract

Women with positive BRCA 1 and 2 gene mutations and HBOC are high-risk populations who may develop ovarian cancer, but there are also women who have a higher incidence of ovarian cancer due to age, ethnicity, or health insurance. Ovarian cancer is the number one fatal disease for females in the United States due to the lack of reliable screening methods. Clinicians need to develop and implement cost effective strategies that encourage females to take advantage of early detection screenings. Evidence from controlled screening trials has supported molecular and genetic marker research to identify ovarian cancerous tumors. CA-125 has been identified as the most supported for the detection of ovarian cancer before symptoms arise. A combination of CA-125 and transvaginal ultrasonography was found to predict ovarian cancer, but the cancers detected through screening and eventual biopsies were late stage. Screening methods will provide early detection in order to treat ovarian cancer.

Detection of Ovarian Cancer: The Benefits of CA125, Ultrasound or Both

Ovarian cancer is a devastating disease that offers little chance for survival, and it is a silent killer.  The strongest known risk factor for ovarian cancer is family history. In fact, there is a 50% risk that children born to parents with positive breast cancer susceptibility gene 1 and 2(BRCA) have a higher predisposition for developing ovarian cancer (Isaacs, Fletcher & Peshkin 2013).  Nevertheless, Isaacs, Fletcher and Peshkin (2013) have asserted that discerning a familial history with hereditary breast and ovarian cancer (HBOC) from a family history of nonexistent HBOC is imperative in diagnosing patterns of hereditary.

Early treatment and detection have been found to be effective; however, Isaacs, Fletcher, and Peshkin (2013) revealed that there is a lack of screening for the general female population. Consequently, Morris, Sands, and Smith (2010) have reported that ovarian cancer is the number one fatal disease for females in the United States due to the lack of reliable screening methods. Because ovarian cancer’s early symptoms often go unnoticed, some women may not recognize the subtle symptoms, and they fail to go to the doctor until it is too late. In addition, there is the issue of how long it would take to diagnose a symptomatic patient. Moreover, a late diagnosis of the later stages of ovarian cancer may not necessarily alter the patient’s outcome. Isaacs, Fletcher, and Peshkin (2013) have suggested that serum tumor markers such as CA-125 and ultrasonography will accurately predict ovarian cancer. This literature review will examine the benefits and disadvantages of transvaginal ultrasound and tumor marker CA-125 and find evidence to answer the clinical question: “In adult females with family history of ovarian cancer, will transvaginal ultrasound or CA-125 have a better positive or negative predictive value for ovarian cancer?”

Methods

The University of Maryland, Baltimore Library was used to access peer-reviewed journal articles. A comprehensive review of the literature from PubMed, Up-To-Date and Google Scholar of key phrases ‘ovarian cancer diagnosis,’ ‘ultrasound and CA125,’ and ‘family history of ovarian cancer’ were identified to find resources reported as of the end of 2008. Inclusionary criteria involved asymptomatic and symptomatic patients, and the articles used were specific to both CA-125 and ultrasound including predictive values for diagnosis.  Exclusionary criteria were comprised of patients who had a previous ovarian cancer diagnosis or diagnosis through other modalities other than CA-125 and ultrasound.  A selected review of this literature will be presented.

Literature Review

The problem that will be addressed is the likelihood of family history accurately predicting an adult female’s propensity towards ovarian cancer. The intent of this literature review is to find evidence that suggests if transvaginal ultrasound or CA-125 has a better positive or negative predictive value for ovarian cancer.

Rein et al. (2011) revealed that tumor markers, such as CA-125, have been found to be effective in early diagnosis, but they have not gained widespread awareness. Nevertheless, CA-125 has been identified as the most supported for the detection of ovarian cancer before symptoms arise (Rein et al., 2011).  In their review, Rein et al. (2011) had found that evidence from controlled screening trials that supported molecular and genetic marker research to identify ovarian tumors. Moreover, tumor markers are less invasive and easier to obtain, so they seem to be a more practical screening approach (Rein et al., 2011). In addition, forgoing the need for tissue samples will increase the likelihood of early diagnosis (Rein et al., 2011). Essentially, clinicians need to find reliable and cost-effective means that encourage females to take advantage of early detection screenings.

Partridge et al. (2009) predicted that screening with serum CA-125 or transvaginal ultrasounds (TVU) would diminish the mortality rates of ovarian cancer. In their sample, 34, 261 females, aged 54-74 years of age, received at least one screening test of TVU, CA-125, or both during a four-year trial in ten screening facilities (Partridge et al., 2009).  Partridge et al. (2009) indicated that the TVU’s results were positive if the ovaries, cysts occupying the ovaries, or any projection invading the ovaries had a volume > 10 cm3. The serum CA-125 was drawn and frozen, and its levels were sent to an immunology lab for analysis (Partridge et al., 2009).  A CA-125 level ≥ 35 U/ml was indicative of a positive value (Partridge et al., 2009).  For the trial, TVU showed a decline in positive screening while CA-125 produced positive screens. The variability of positive screenings amongst the ten screening facilities was low and yielded approximately 35% positive screens with TVU and 20% positive screens with CA-125 (Partridge et al., 2009). Furthermore, the cancers detected through screening and eventual biopsies were late stage III/IV cancers (Partridge et al., 2009). Partridge et al. (2009) has noted that out of the 89 participants diagnosed with ovarian cancer, the screenings diagnosed 60. Therefore, their results suggest that screening is still more predicative of late stage diagnosis (Partridge et al., 2009).

The late stage diagnosis is problematic because early detection alleviates the risk for ovarian cancer mortalities. Long and Kauff (2013) suggested CA-125 and TVU are sensitive enough to detect ovarian cancer, but they are lacking in supplying diagnoses at an early stage. Essentially, specific requirements need to be met in order for cancer screening to be effective (Long & Kauff, 2013). Long and Kauff (2013) noted that the United Kingdom Familial Ovarian Cancer Screen Study (UK FOCSS) hypothesized that one requirement could involve a woman’s family history (Long & Kauff, 2013). Women with a 10% risk of developing ovarian or fallopian tube cancer were screened using TVU and CA-125, and the researchers found a 25.5% positive predictive value from screening (Long & Kauff, 2013). While Long and Kauff (2013) reported that the UK FOCSS provided valuable data to support screening women with HBNO in their family, their requirements may have been too stringent. For example, women were required to have BRCA 1 or 2 mutation or family history. While women with positive BRCA 1 and 2 gene mutation and family history have an increased susceptibility for developing ovarian cancer (Partridge et al., 2009), there are also women who have a higher incidence of ovarian cancer due to other issues such as age, ethnicity, or a lack of health insurance (Isaacs, Fletcher, and Peshkin, 2013; Morris, Sands, & Smith, 2010). Nonetheless, while the results suggest a family history is not the best requirement, it does reveal a need for genetic testing.

Hippisley-Cox and Coupland (2012) used an algorithm to demonstrate the absolute risk of women developing ovarian cancer based on their family history, age, and symptoms. Patients offered their physicians non-specific symptoms and the information was applied to the algorithm in order to assess their level of care for the cancer patient (Hippisley-Cox & Coupland, 2012) While the algorithm does not diagnose women with ovarian cancer, it is a good indicator for possible diagnosis in the future (Hippisley-Cox & Coupland, 2012). For predictive values, chronic and absolute risk factors were used. Hippisley-Cox and Coupland (2012) found that after independent validation in an external cohort, the algorithm has offered decent discrimination and calibration, so it could potentially be a viable method to identify females who were at high risk of ovarian cancer. Incidentally, Hippisley-Cox and Coupland’s (2012) two-year study revealed that out of 63% of ovarian cancers diagnoses, only 10% of the women were considered to have high-risk predispositions; therefore, it seems a variety of women may be in danger of ovarian cancer, yet they may be unaware of its subtle symptoms.

Hess, Stehman, Method, Weathers, and Gupta (2012) have concurred that the lack of early detection and screening is detrimental to females. In their study, Hess et al. (2012) reviewed patients’ medical records before they visited a gynecologic oncology doctor’s office and assessed their prior medical history. A decision tree model identified the patients’ actions after the visit, and Hess et al. (2012) determined that there were less health care visits yet rapid diagnoses for patients when they went to gynecologic oncologists. Specifically, Hess et al. (2012) noted that a Monte Carlo simulation of the decision tree suggested that the majority of the hypothetical patients who were diagnosed with ovarian cancer were in the later stages of the disease. The time of recognition revealed the avenues patients should explore in order to receive the timely treatment that would reduce ovarian cancer mortality rates (Hess et al., 2012). One type of treatment is immunotherapy anti-PD-1. In addition, Hess et al. (2012) had determined that specific care management can offer better advice and speedier diagnosis if the patients have suspected gynecologic problems. While Hess et al. (2012) explained that further research needs to be conducted on the approach to early diagnoses of ovarian cancer and the primary care providers’ roles in recognizing signs and symptoms, it is research that affords patients with fast, efficient, and lifesaving diagnoses.

Conclusions

Based on the literature review, researchers had identified that ovarian cancer posed a deadly risk when not diagnosed in a timely matter and early detection by screening has been found to be effective (Isaacs, Fletcher & Peshkin, 2013; Morris, Sands, and Smith, 2010; Partridge et al., 2009; Long & Kauff, 2013; Hippisley-Cox & Coupland, 2012; Rein et al., 2011; Hess, Stehman, Method, Weathers, and Gupta, 2012). Hess, Stehman, Method, Weathers, and Gupta (2012) have asserted that early treatment and detection lay in the hands of primary care providers, so it seems that in order to provide women with crucial information regarding ovarian cancer, screenings are imperative. Rein et al. (2011) have emphasized markers such as CA-125 are both cost effective and have demonstrated evidence that reveals reliability. Further research should focus on CA-125 to solidify its stability and at the same time improve the sensitivity and specificity of ovarian cancer detection. While TVU has been a reliable indicator of ovarian cancer, research has suggested that it is an instrument that reveals ovarian cancer in its latter stages. However, a combination of both may be the most appropriate when a woman has a family history prone to HBOC. In this case, genetic counseling during the patient’s visit may be beneficial.

Discussion

Essentially, screening should be available for all women in order to reduce ovarian cancer’s high mortality rates. While particular populations may be susceptible to the disease based on their family history or age, early detection provides early treatment. CA-125 and TVU have evidence that shows they are reliable screening procedures; however, they are in need of further research to finalize their reliability. While government policies such as state insurance may not find screening procedures to be cost-effective approaches to detecting cancer, the cost of hospitalizations due to its severity are immense. Therefore, along with screening, genetic counseling should be provided to patients to understand their risks. Based on the literature review’s findings, family history will likely establish a female’s risk factors. However, lifestyle must be a further consideration due to the women who are diagnosed with ovarian cancer without family hereditary. Therefore, protocol, with the screenings based on this research, should be implemented in health care facilities and provided to their female patients for early detection.

References

Hess, L. M., Stehman, F. B., Method, M. W., Weathers, T. D., & Gupta, P. (2012) Identification of the optimal pathway to reach an accurate diagnosis in the absence of an early detection strategy for ovarian cancer. Gynecologic Oncology, 127(2012), 564-568.

Hippisley-Cox, J., & Coupland, C. (2012). Identifying women with suspected ovarian cancer in primary care: derivation and validation of algorithm. BMJ. doi:10.1136/bmj. d8009

Isaacs, C., Fletcher, S., & Peshkin, B. (2013). Management of hereditary breast and ovarian cancer syndrome and patients with BRCA mutations. In UpToDate. Retrieved May 27, 2013, from http://www.uptodate.com/contents/management-of-hereditary-breast-and-ovarian-cancer-syndrome-and-patients-with-brca-mutations?topicKey=ONC%2F758&elapsedTimeMs=5&view=print&displayedView=ful

Long, K. C., & Kauff, N. D. (2013, January 1). Screening for familial ovarian cancer: a ray of hope and a light to steer by [Editorial] [Electronic version]. Journal of Oncology, 31(1), 8-10.

Morris, C. R., Sands, M. T., & Smith, L. H. (2010). Ovarian cancer: predictors of early-stage diagnosis. Cancer Causes Control, 21, 1203-1211. doi:10:1007/s10552-010-9547-0

Rein, B. J., Gupta, S., Dada, R., Safi, J., Michener, C., & Agarwal, A. (2011). Potential markers for detection and monitoring of ovarian cancer. Journal of Oncology, 2011. doi:10:1155/2011/475983

Partridge, E., Greenlee, R., Xu, J., Kreimer, A., Williams, C., Riley, T., & Reding, D. (2009). Results from four rounds of ovarian cancer screening in randomized trial. Obstet Gynecol, 113(4), 775-782.