Serum CA-125 Testing Research Articles

Serum CA-125 for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis

BackgroundPulmonary tuberculosis (PTB) remains the world’s deadliest infectious killer. Serum CA-125 test are useful in the diagnosis of PTB. Although studies on the relation between CA-125 and PTB have been reported, the specificity and sensitivity of serum CA-125 in diagnosing PTB vary widely among different studies. The present study was performed to evaluate the accuracy of CA-125 for the diagnosis of PTB via a meta-analysis of data obtained from previous studies.MethodsEnglish and Chinese medical electronic databases were searched for eligible studies published up to February 2020. STATA software was used to obtain a pooled estimation of the diagnostic accuracy of CA-125 and analyze the heterogeneity of the recruited studies. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the obtained studies.ResultsA total of 16 articles were included in this study. The pooled sensitivity and specificity of CA-125 were 0.85 [95% confidence interval (CI) 0.75–0.91] and 0.87 (95% CI 0.78–0.93), respectively. Moreover, the pooled positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic odds ratio (DOR) of CA-125 were 6.65 (95% CI 3.62–12.20), 0.18 (95% CI 0.10–0.31), and 37.82 (95% CI 13.17–108.60), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.93.ConclusionsTaken together, the results indicate that serum CA-125 presents potential practical value for diagnosing PTB, but its clinical applicability must be further examined.

The accuracy of preoperative serum CA-125 levels to predict lymph node metastasis in a population of South African women with endometrial carcinoma

Background: The purpose of the study was to evaluate the predictive value of serum CA-125 levels in the preoperative assessment of endometrial carcinoma in a setting where late presentation is common.Method: This retrospective study evaluated women with pathologically proven endometrial carcinoma scheduled for surgery between January 2012 and January 2017, who had preoperative serum CA-125 test results. The association of CA-125 with a variety of histological factors was evaluated using Spearman’s correlation and receiver operator characteristic (ROC) curves to evaluate sensitivity and specificity.Results: Fifty-eight patients were included in the study, 34 (58.6%) of whom were FIGO stage II–IV. Elevated CA-125 levels were significantly correlated with late FIGO stage (p < 0.001), myometrial invasion (p < 0.001) and lymph node metastases (p < 0.001). The most appropriate cut-off point of CA-125, where an increase in sensitivity was not associated with a fall-off in specificity, was 20 IU/ml, reaching a sensitivity of 90% and a specificity of 67% for detection of lymph node metastases.Conclusion: Among this group of women with endometrial cancer, the preoperative serum CA-125 level was associated with lymph node metastases and we found a CA-125 of 20 IU/ml or more to be predictive. These findings suggest that, among similar populations, CA-125 could be done preoperatively and could be used to determine the need for node dissection. Since our findings are from a small retrospective cohort, this should be validated in a prospective study on early stage disease.

Comparison of Longitudinal CA125 Algorithms as a First-Line Screen for Ovarian Cancer in the General Population.

Purpose: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), women in the multimodal (MMS) arm had a serum CA125 test (first-line), with those at increased risk, having repeat CA125/ultrasound (second-line test). CA125 was interpreted using the "Risk of Ovarian Cancer Algorithm" (ROCA). We report on performance of other serial algorithms and a single CA125 threshold as a first-line screen in the UKCTOCS dataset.Experimental Design: 50,083 post-menopausal women who attended 346,806 MMS screens were randomly split into training and validation sets, following stratification into cases (ovarian/tubal/peritoneal cancers) and controls. The two longitudinal algorithms, a new serial algorithm, method of mean trends (MMT) and the parametric empirical Bayes (PEB) were trained in the training set and tested in the blinded validation set and the performance characteristics, including that of a single CA125 threshold, were compared.Results: The area under receiver operator curve (AUC) was significantly higher (P = 0.01) for MMT (0.921) compared with CA125 single threshold (0.884). At a specificity of 89.5%, sensitivities for MMT [86.5%; 95% confidence interval (CI), 78.4-91.9] and PEB (88.5%; 95% CI, 80.6-93.4) were similar to that reported for ROCA (sensitivity 87.1%; specificity 87.6%; AUC 0.915) and significantly higher than the single CA125 threshold (73.1%; 95% CI, 63.6-80.8).Conclusions: These findings from the largest available serial CA125 dataset in the general population provide definitive evidence that longitudinal algorithms are significantly superior to simple cutoff values for ovarian cancer screening. Use of these newer algorithms requires incorporation into a multimodal strategy. The results highlight the importance of incorporating serial change in biomarker levels in cancer screening/early detection strategies. Clin Cancer Res; 24(19); 4726-33. ©2018 AACR.

Detecting Asymptomatic Recurrence in Early-Stage Endometrial Cancer: The Value of Vaginal Cytology, Imaging Studies, and CA-125.

The aim of this study was to evaluate the value of vaginal cytology, imaging modalities, and serum CA-125 in detecting asymptomatic recurrence during posttreatment surveillance for early-stage endometrial cancer. A retrospective analysis was conducted on patients with stage I to II endometrial cancer who received primary surgical treatment at Seoul National University Hospital between 2000 and 2011. Clinicopathologic characteristics and surveillance test data were obtained from medical records. The total numbers of vaginal cytologies, imaging studies, and serum CA-125 levels performed during surveillance or until recurrence were evaluated, and the number of tests needed to detect each asymptomatic recurrence was calculated. A total of 389 patients were identified, together with a total of 3323 vaginal cytologies, 1025 chest x-rays, 1177 abdominal computed tomography (CT) scans, 98 magnetic resonance imaging scans, 163 positron emission tomography/CT scans, 298 ultrasonographies, and 3335 serum CA-125 results obtained during the surveillance period. Recurrence was detected in 14 patients (3.6%). Ten of these cases were asymptomatic, of which six were identified through CT scans and four were identified through elevated serum CA-125 levels. Most of the patients (7/10) with asymptomatic recurrences had localized recurrence patterns, five of whom underwent curative-intent resection and survived. The number of CA-125 tests needed to identify 1 asymptomatic recurrence was 839, whereas the number of CT scans needed to achieve the same result was 196. Other imaging modalities and vaginal cytology did not detect asymptomatic recurrence. For posttreatment surveillance in early-stage endometrial cancer, vaginal cytology and imaging modalities such as chest x-ray, magnetic resonance imaging, positron emission tomography/CT, and ultrasonography have low utility. Routine CT scans and serum CA-125 testing may be useful for detecting asymptomatic recurrence.

Usefulness of CA125 in the differential diagnosis of uterine adenomyosis and myoma

ObjectivesTo evaluate the usefulness of CA125 levels in the differential diagnosis of adenomyosis and myoma. This has been addressed by few, if any, previous studies. Study designPreoperative serum CA125 levels were measured in 2149 women who were diagnosed at total hysterectomy as having adenomyosis, myoma, endometriosis, and/or normal pelvis. Their medical records were retrieved and reviewed. ResultsThe mean serum CA125 level in the adenomyosis patients was significantly greater than that in the patients diagnosed with myoma (65.21±96.60U/mL vs.12.86±14.23U/mL, respectively; P<0.001). In the differential diagnosis of adenomyosis and myoma, the cut-off serum CA125 level with the highest accuracy (78.8%) and highest diagnostic value (61.2%) was 19U/mL. Using this cut-off value, the negative predictive value was 69.5%, and the positive predictive value was 76.5%. These results are clearly superior to those of the empirical single cut-off value of 35U/mL. Receiver operating characteristic curve analysis revealed the area under the curve for differentiating adenomyosis from myoma was 0.776, indicating good diagnostic performance. ConclusionIn the differential diagnosis of adenomyosis and myoma, cut-off values for CA125, particularly the cut-off value of 19U/mL, provide improved diagnostic performance. Serum CA125 testing can be performed during the initial screening of women with possible adenomyosis to differentiate this condition from myoma, although the diagnostic accuracy of using CA125 testing alone is limited.

Cost-effectiveness of serum CA125 compared to transvaginal ultrasound as a screening test for ovarian cancer: a systematic review protocol

Review question/objective The objective of this review is to synthesize the evidence from economic evaluations of the resource use and cost effectiveness of serum CA125 testing compared to transvaginal ultrasound screening for ovarian cancer. The review questions are: What are the estimates of the cost effectiveness of serum CA125 testing in females of any age compared to the use of transvaginal ultrasound testing for ovarian cancer screening? If the evidence presents a wide range of cost effectiveness measures, can any conclusions be drawn regarding the circumstances in which serum CA125 is likely to be more effective and less costly than transvaginal ultrasound as a screening test for ovarian cancer? The ultimate objective of the review is to provide information that can be used by policy makers and administrators to make evidence-informed recommendations regarding ovarian cancer screening. Inclusion criteria Types of participants The review will consider economic evaluation studies in which the participants are females of any age who have had serum CA125 or transvaginal ultrasound testing for ovarian cancer screening. Females of any age, living in any country will be considered for inclusion. Types of intervention(s) and comparator(s) The intervention of interest for this review of economic evaluation of evidence is serum CA125 screening for ovarian cancer. The comparator of interest is transvaginal ultrasonography screening method for ovarian cancer. To be included, studies must have estimated the resource use/uses relative to the benefits/effectiveness of the serum CA125 screening method compared to the transvaginal ultrasound screening test for ovarian cancer. The review will consider all economic evaluations that have focused on the two screening methods (serum CA125 and transvaginal ultrasound) regardless of the perspective (societal, individual/patient, health system). The review will exclude studies using serum CA125 testing as a marker for tumor or disease progression. Types of outcomes This review will consider studies that include cost utility or/and cost benefit or/and cost effectiveness outcome measures for the intervention (Serum CA125) and comparator (transvaginal sonogram).

Computed tomography adnexal mass score to estimate risk for ovarian cancer

We wish to develop a CT scan-based scoring system which estimates the probability of adnexal mass malignancy. Patients (324) undergoing adnexal mass surgery were recruited into the study from June 1, 2002, to January 1, 2009. All study patients had a preoperative CT scan and serum CA-125 test. CT scan abnormalities included any solid tumor components, ascites, and pelvic or abdominal lymphadenopathy and omental caking. There were 225 (70%) benign and 99 (30%) malignant ovarian masses. Using logistic regression with the area under the curve of the receiver operating curve of 82%, the cancer probability was determined by the equation. e(-3.6372+0.0306*(A)+0.001*(C)+1.551*(D)+1.7377*(E)+2.76*(F)) / 1+e(-3.6372+0.0306*(A)+0.001*(B)+0.876*(C)+1.551*(D)+1.7377*(E)+2.76*(F)) where A = age, B = CA-125, C = solid adnexal mass is 1 and cystic is 0, D = ascites is 1, E = omental caking is 1 and absence is 0, F = node size ≥1 cm is 1 and <1 cm is 0 value. The natural logarithm e is a constant [2.718281828]. For example, for a woman of age 60, CA-125 = 50 U/mL, with solid adnexal mass, ascites, omental caking, and lymphadenopathy, the probability is 0.994. Hence, this woman has a 99.4% probability of having cancer. The computed tomography adnexal mass score combines CT scan findings, CA-125, and patient age into an equation to predict the malignant probability of an adnexal mass.

Preoperative prediction model of lymph node metastasis in endometrial cancer.

We aimed to develop a preoperative prediction model identifying the low-risk group for lymph node metastasis in endometrial cancer. In 110 patients who underwent preoperative magnetic resonance imaging and serum CA-125 test, logistic analysis was performed to identify predictors. The coefficients obtained from logistic regression were used to construct a scoring system, and a receiver operator characteristic curve was created. Lymph node metastases were found in 14 (12.7%) of 110 patients. After multivariate logistic regression analysis, histologic grade, preoperative CA-125 levels, disease extent, and myometrial invasion assessed by magnetic resonance imaging were selected as viable predictors. The scoring system was internally validated using bootstrapping (P < 0.001), and receiver operator characteristic curve yielded the area under the curve of 0.902. The patients with the score of 0 or 1 (57.3%) were identified as a low-risk group, and no nodal metastasis was observed among them (negative predictive value, 100%: 95% confidence interval, 94.3%-100%). The current study suggests that preoperative prediction system to identify the risk of lymph node metastasis is feasible. This model may be useful in preoperative counseling about cost and benefit of systemic lymph node dissection.

A randomized study of screening for ovarian cancer: a multicenter study in Japan

Ovarian cancer is common in women from developed countries. We designed a prospective randomized controlled trial of ovarian cancer screening to establish an improved strategy for the early detection of cancers. Asymptomatic postmenopausal women were randomly assigned between 1985 and 1999 to either an intervention group (n = 41,688) or a control group (n = 40,799) in a ratio of 1:1, with follow-up of mean 9.2 years, in Shizuoka district, Japan. The original intention was to offer women in the intervention group annual screens by gynecological examination (sequential pelvic ultrasound [US] and serum CA125 test). Women with abnormal US findings and/or raised CA125 values were referred for surgical investigation by a gynecological oncologist. In December 2002, the code was broken and the Shizuoka Cohort Study of Ovarian Cancer Screening and Shizuoka Cancer Registry were searched to determine both malignant and nonmalignant diagnoses. Twenty-seven cancers were detected in the 41,688-screened women. Eight more cancers were diagnosed outside the screening program. Detection rates of ovarian cancer were 0.31 per 1000 at the prevalent screen and 0.38-0.74 per 1000 at subsequent screens; they increased with successive screening rounds. Among the 40,779 control women, 32 women developed ovarian cancer. The proportion of stage I ovarian cancer was higher in the screened group (63%) than in the control group (38%), which did not reach statistical significance (P = 0.2285). This is to our knowledge the first prospective randomized report of the ovarian cancer screening. The rise in the detection of early-stage ovarian cancer in asymptomatic postmenopausal women is not significant, but future decisions on screening policy should be informed by further follow-up from this trial.

Gynecologic Cancer Prevention in Lynch Syndrome/Hereditary Nonpolyposis Colorectal Cancer Families

Women carrying a Lynch syndrome/hereditary nonpolyposis colorectal cancer (HNPCC) germline mutation have an estimated 40% to 60% lifetime risk of developing endometrial cancer and a 10% to 12% risk of ovarian cancer. The incidence of gynecological cancer in these women is at least as great as that of colorectal cancer and possibly greater. The median age of incidence is in the fourth decade with a trend toward earlier stage and grade, but one-fourth of affected women present with high-risk features that warrant adjuvant therapy. Current practice is to identify women from high-risk families so that genetic testing may be considered. It remains unclear whether high-risk women should be followed or undergo prophylactic surgery. The investigators developed a decision analytic model with which to compare management strategies for women carrying a Lynch/HNPCC mutation. Three approaches were analyzed: lifetime annual gynecological examinations; annual screening by transvaginal ultrasonography, endometrial biopsy, and serum CA-125 testing; and prophylactic hysterectomy with bilateral salpingo-oophorectomy at age 30 years. Relevant studies were reviewed, and cancer mortality outcomes were estimated from the Surveillance, Epidemiology, and End Results database for the years 1988-2001. In the surgical arm, 0.0056% of women were diagnosed with ovarian cancer and 0.0060% with endometrial cancer. The numbers increased to 3.7% and 18.4%, respectively, in women who were screened annually and who had surgery if screen-positive, and to 8.3% and 48.7% in those having annual examinations and were diagnosed with interval cancers. Surgery was associated with the longest expected survival time, 80 years, followed by screening at 79 years and annual examinations at 77 years. Surgery still yielded the most expected life years when starting at age 30 and discounting life years at 3%. Comparing prophylactic surgery with screening, 75 surgeries would be needed to save one woman's entire life. In contrast, only 28 preventive surgeries would be needed to prevent 1 case of ovarian cancer, and 6 to prevent 1 case of endometrial cancer. This analysis suggests that prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective approach to preventing gynecological cancers in Lynch/HNPCC women.

Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study

The outcome of screening and prophylactic surgery in 269 women at high risk of hereditary ovarian cancer is reported. Screening was performed using transvaginal ultrasound and serum CA125 testing. Mean follow-up was 26 months (583 person-years). A total of 113 (42%) of 269 women had a pathogenic BRCA1 or BRCA2 mutation, and 127 (47%) of 269 women underwent salpingo-oophorectomy. No occult cancers were found. In eight women having both elevated CA125 levels and abnormal ultrasound findings, a malignancy was found. Four of these cancers (one borderline, one stage Ia, one stage IIIb, and one stage IIIc ovarian or peritoneal cancer) were detected at the first screening visit. One stage IIIb and one stage IIIc cancer were detected at the second screening visit after 12 months, and two interval stage IIIc and IV cancers were detected 8 and 10 months after the first screening visit. No peritoneal carcinoma was found among those 114 women who underwent bilateral salpingo-oophorectomy with normal or benign pathology results, after a mean follow-up of 16 months (152 person-years). We conclude that the efficacy of screening women at high risk of ovarian cancer seems poor because the majority of cancers were detected at an advanced stage.

Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study

The outcome of screening and prophylactic surgery in 269 women at high risk of hereditary ovarian cancer is reported. Screening was performed using transvaginal ultrasound and serum CA125 testing. Mean follow-up was 26 months (583 person-years). A total of 113 (42%) of 269 women had a pathogenic BRCA1 or BRCA2 mutation, and 127 (47%) of 269 women underwent salpingo-oophorectomy. No occult cancers were found. In eight women having both elevated CA125 levels and abnormal ultrasound findings, a malignancy was found. Four of these cancers (one borderline, one stage Ia, one stage IIIb, and one stage IIIc ovarian or peritoneal cancer) were detected at the first screening visit. One stage IIIb and one stage IIIc cancer were detected at the second screening visit after 12 months, and two interval stage IIIc and IV cancers were detected 8 and 10 months after the first screening visit. No peritoneal carcinoma was found among those 114 women who underwent bilateral salpingo-oophorectomy with normal or benign pathology results, after a mean follow-up of 16 months (152 person-years). We conclude that the efficacy of screening women at high risk of ovarian cancer seems poor because the majority of cancers were detected at an advanced stage.

Usefulness and limits of CA-125 in diagnosis of endometriosis without associated ovarian endometriomas

The aim of this study was to evaluate the diagnostic significance of CA-125 for endometriosis without ovarian endometriomas. Preoperative serum CA-125 levels were measured in 775 consecutive women diagnosed by laparoscopy or laparotomy with endometriosis, adenomyosis, leiomyomas, or normal pelvis. Receiver operating characteristic curve analysis revealed that the area under the curve for endometriosis without endometriomas was 0.788, significantly smaller than that for endometriosis with endometriomas (0.935, P < 0.05). In diagnosis of endometriosis without endometriomas, both the maximal accuracy of 78.8% and the maximal diagnostic value of 61.2% were obtained at the cutoff value of 20 U/mL. Negative predictive value was 78.0% at the cutoff value of 20 U/mL, whereas positive predictive value was 92.9% at the cutoff value of 30 U/mL. This range is clearly superior to the empirical single cutoff of 35 U/mL. In the diagnosis of endometriosis without endometriomas, combined use of two cutoff values for CA-125, 20 and 30 U/mL, provides improved diagnostic performance. However, the accuracy of using only CA-125 testing for diagnosis is still limited. Serum CA-125 testing can be done during initial screenings of women with possible endometriosis.