Clinical UM Guideline

This document addresses tumor marker cancer antigen 125 (CA-125) testing.

Note: Please see the following related documents for additional information:

• CG-LAB-33 Carcinoembryonic Antigen Testing
• CG-LAB-35 Cancer Antigen 19-9 Testing

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

Medically Necessary:

1. CA-125 testing is considered medically necessary for either clinical scenario (A or B) and the following conditions (C):
   1. As part of initial evaluation for suspected or diagnosed disease; or
   2. To determine whether residual tumor exists post-surgical therapy; 
      and
   3. Conditions:
      1. Appendiceal adenocarcinoma; or
      2. Endometrial cancer; or
      3. Ovarian, primary peritoneal or fallopian tube cancer; or
      4. Pancreatic adenocarcinoma; or
      5. Peritoneal mesothelioma; or
      6. Uterine neoplasms (endometrial cancer and uterine sarcoma).
          
2. CA-125 testing is considered medically necessary for evaluation of a pelvic or abdominal mass when malignancy is suspected.
    
3. CA-125 testing is considered medically necessary when there are signs or symptoms suggestive of ovarian cancer.
    
4. CA-125 testing is considered medically necessary for the surveillance of ovarian cancer in individuals with hereditary breast and ovarian cancer syndrome starting at age 30 years until the time they choose to pursue risk-reducing bilateral salpingo-oophorectomy.
    
5. Repeat CA-125 testing* is considered medically necessary when used to:
   1. Monitor response to therapy; or
   2. Assess for recurrence when suggested by clinical factors.

*See Discussion/General Information section below for additional information on medical society guideline recommendations regarding the clinical appropriateness of testing frequency.

Not Medically Necessary:

CA-125 testing is considered not medically necessary when the above criteria are not met, including, but not limited to, as a screening test in an average risk individual.

This document describes clinical studies and expert recommendations, and explains when cancer antigen 125 (CA-125) testing is clinically appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

CA-125 is a tumor marker, which is a substance that can sometimes be found at higher levels in the blood when cancer is present. CA-125 testing may help to check for some cancers, such as ovarian cancer, fallopian tube cancer, primary peritoneal cancer, endometrial cancer, uterine sarcoma, pancreatic cancer, appendiceal cancer, and peritoneal mesothelioma. This test may also help check a pelvic or belly mass when cancer is suspected. CA-125 can also help to see if cancer treatment is working or if cancer may have come back. CA-125 is not a good screening test for people without any signs or symptoms of ovarian cancer, since levels can be high for reasons other than cancer, such as endometriosis, pregnancy, or pelvic infection. This can lead to false-positive results, which means the test can suggest cancer when cancer is not present.

What the Studies Show

CA-125 testing can be useful in certain cancer care settings. One study found that CA-125 levels obtained during treatment were associated with the risk of disease progression or death among individuals with advanced ovarian cancer. The study had limits because it was done at one center. Studies do not support CA-125 as a routine screening test for people at average risk who do not have symptoms. In a large ovarian cancer screening trial, yearly CA-125 testing with vaginal ultrasound did not lower deaths from ovarian cancer. Other studies found that false-positive results can lead to more tests or unnecessary surgery.

When is CA-125 Testing Clinically Appropriate?

CA-125 testing may be clinically appropriate in these situations:

• It is part of the first evaluation for suspected or diagnosed disease; or
• It is used to see if tumor remains after surgery; and
• The person has one of these conditions:
  • Appendiceal adenocarcinoma;
  • Endometrial cancer;
  • Ovarian cancer, primary peritoneal cancer, or fallopian tube cancer;
  • Pancreatic adenocarcinoma;
  • Peritoneal mesothelioma;
  • Uterine neoplasms, including endometrial cancer and uterine sarcoma.

CA-125 testing may also be clinically appropriate when:

• A pelvic or belly mass is being checked and cancer is suspected;
• A person has signs or symptoms that suggest ovarian cancer;
• A person with hereditary breast and ovarian cancer syndrome is being watched for ovarian cancer starting at age 30 until they choose surgery to lower risk by removing both ovaries and fallopian tubes; or

Repeat testing is used to check response to treatment or to check if cancer has come back when clinical factors suggest this.

When is this not Clinically Appropriate?

CA-125 testing is not clinically appropriate when the criteria listed above are not met. This includes routine screening for a person at average risk who does not have signs or symptoms. The possible benefit of CA-125 testing depends on the person’s risk, symptoms, and cancer history. The risks include false-positive results, extra testing, and treatment that may not help.

Return to Description

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Medically Necessary:

When services are Not Medically Necessary:
For the procedure codes listed above for all other diagnoses not listed.

Summary

Cancer antigen 125 (CA-125) is a type of tumor marker. It is commonly expressed by epithelial ovarian neoplasms and other tissues, such as cells lining the endometrium, fallopian tubes, pleura, peritoneum, and pericardium. High levels of tumor markers such as CA-125 in the blood may also be a sign of cancer. CA-125 testing may be used to monitor how well cancer treatments are working or if cancer has reoccurred, and such use is recommended by several organizations, including the American College of Obstetricians and Gynecologists (ACOG), the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network^® (NCCN), and the United States Preventive Services Task Force (USPSTF). The Centers for Medicare & Medicaid Services (CMS) also has a National Coverage Determination (NCD) to address CA-125 which includes several covered indications. However, elevated levels of CA-125 may also be present in instances of endometriosis, pregnancy, pelvic inflammatory disease, and nongynecologic cancer. These instances of potential fluctuation in CA-125 levels can lead to false positive results and limited specificity.

Discussion

Ovarian Cancer

Signs and symptoms suggestive of ovarian cancer include ascites, abdominal distension, bloating, pelvic/abdominal pain, difficulty eating or feeling full quickly and urinary symptoms.

The NCCN guidelines for Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer (NCCN, 2026) recommend CA-125 testing for those who present with a suspicious or palpable pelvic mass on abdominal/pelvic exam, and/or ascites, or abdominal distention. The NCCN also recommends CA-125 testing for those with symptoms that are not linked to another definitive source of malignancy (that is, bloating, pelvic/abdominal pain, difficulty eating or feeling full quickly, and urinary symptoms [urgency or frequency]). In addition, the NCCN guidelines recommend CA-125 testing for individuals with a new diagnosis of ovarian cancer after a recent surgical procedure and as part of a preoperative workup. This is based on data showing that CA-125 levels correlate with the extent of the disease, the clinical course of the disease which can assist in treatment planning, monitoring response to therapy, and surveillance for recurrence. The NCCN guideline also notes “Primary peritoneal and fallopian tube cancers are treated in the same manner as epithelial ovarian cancer.” The NCCN guidelines note it is appropriate to monitor for ovarian cancer with CA-125 as clinically indicated prior to each cycle of chemotherapy and after completion of primary therapy. Monitoring and follow-up may be appropriate after primary treatment if CA-125 was initially elevated. Testing for recurrent disease may be appropriate with a rising CA-125 if there was no previous chemotherapy, a serially rising CA-125 if there was previous chemotherapy, and for platinum-sensitive disease if there is a rising CA-125 without radiographic evidence of disease.

A 2025 study by Yin and colleagues reported on participants with advanced ovarian cancer and sought to determine how CA-125 levels may forecast treatment results. For 819 individuals, CA-125 levels were obtained on day 1 of each treatment cycle, then every 3 months for the first 3 years after treatment ended, then every 6 months for 2 more years, then annually. Primary outcome was progression-free survival (PFS) with a secondary outcome of overall survival (OS). The authors noted those who had low CA-125 levels at baseline and remained stable throughout treatment had the lowest risk of death or progression of disease. Those with moderate CA-125 levels at baseline that decreased to normal levels following treatment also had a low risk of death or progression of disease. The individuals with high CA-125 levels at baseline had a higher risk of death and disease progression. As such, monitoring CA-125 levels for those with advanced ovarian cancer may assist in monitoring prognosis. The study has limitations including the single center design, which may limit generalizability, particularly for those treated with a different chemotherapy regimen.

The 2021 ASCO Assessment of Adult Women with Ovarian Masses and Treatment of Epithelial Ovarian Cancer guideline (Vanderpuye, 2021) recommends that CA-125 can assist with the diagnosis for postmenopausal women who have symptoms of ovarian cancer. The ASCO guideline also recommends CA-125 for those with symptoms of an ovarian mass.

The 2016 ACOG practice bulletin for Evaluation and Management of Adnexal Masses states that using CA-125 in the evaluation of adnexal masses is most useful in those who are postmenopausal and in identifying nonmucinous epithelial cancer. For those with epithelial ovarian cancer, the CA-125 level is elevated in 80% of individuals.

Surveillance of ovarian cancer, including concurrent transvaginal ultrasound (TVUS) and testing of CA-125, may be appropriate for certain high-risk individuals (specifically, carriers of high penetrance hereditary breast and ovarian cancer syndrome-associated mutations with a strong family history of breast and ovarian cancer) who are of the age range of recommended risk-reducing salpingo-oophorectomy and opt not to pursue it. Studies of concurrent testing with CA-125 and TVUS in high-risk individuals are largely limited to observational studies and have found that most detected cancers (70 to 80 percent) are stage III or IV, with a positive predictive value of 26% for incident screening. The 2026 NCCN guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate along with the American Cancer Society and ACOG suggest that screening may be appropriate in individuals with a diagnosed genetic syndrome that increases the lifetime risk for ovarian and breast cancer and have not or not yet elected to pursue risk-reducing removal of bilateral tubes/ovaries.

Neither current literature nor the 2018 USPSTF support routine screening for ovarian cancer in asymptomatic individuals. The 2017 ACOG committee opinion titled The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk concludes:

The use of transvaginal ultrasonography and tumor markers (such as CA 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results.

In 2016, Pinsky and colleagues reported an analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial with extended mortality follow-up for 6 years. Those in the intervention arm were screened for ovarian cancer with annual trans-vaginal ultrasound and CA-125. There were a total of 187 deaths from ovarian cancer in the intervention arm and 176 deaths in the usual care arm, for a risk-ratio of 1.06 (95% confidence interval [CI], 0.87-1.30). The authors concluded there was no mortality benefit from screening for ovarian cancer with CA-125 and transvaginal ultrasound.

A 1996 prospective study by Jacobs and colleagues analyzed the risk of epithelial ovarian cancer and fallopian tube cancer in asymptomatic, postmenopausal individuals with an elevated CA-125. The authors concluded that an elevated CA-125 was a predictor of ovarian cancer with a relative risk of 35.9 (95% CI, 18.3 to 70.4) during the year after a screen and 14.3 (8.5 to 24.3) during the 5 years after a screen. However, in 2009 Partridge and colleagues (as part of the PLCO Cancer Screening Trial) reported whether annual screening with transvaginal ultrasound and CA-125 reduces ovarian cancer mortality. The authors found “the surgery to detected cancer ratio was 19.5 to 1, and 72% of screen detected cancers were late stage.”

Individuals who are premenopausal have a higher likelihood of having benign gynecologic conditions. However, positive predictive value (PPV) is low even in those who are postmenopausal. In the detection of ovarian cancer in postmenopausal individuals, specificity of a single CA-125 ranged from 98.6% to 99.4% which resulted in a low PPV of 3% (Einhorn, 1992; Zurawski, 1988). PPV for invasive cancer among healthy women ages 55 to 74 years old was similarly low.

Screening for ovarian cancer can be challenging due to the low disease prevalence in those at average risk. Testing strategies should include those with high specificity and sensitivity to minimize false-positive tests. Screening for those at average risk with CA-125 has not been shown to reduce mortality.

Endometrial Cancer

Along with expert review, the 2026 NCCN guideline for Uterine Neoplasms considers CA-125 in the initial evaluation of endometrial cancer and as an aid to a surgical procedure. The NCCN guidelines note it is appropriate to test for CA-125 when there is suspected extrauterine disease as this may be helpful in monitoring clinical response and for surveillance if the CA-125 is initially elevated.

A single-center retrospective chart review by LyBarger in 2022 reported the odds ratio (OR) and relative risks (RR) between preoperative levels of CA-125 and the likelihood of a positive (+) lymph node metastasis and + lymphovascular space invasion. Using preoperative levels of CA-125, risk factors for + lymph node metastasis could distinguish those who are more likely to benefit from lymphadenectomy versus those who would not. There were 890 participants included. There was an increase in the median CA-125 and for those with + lymph node metastasis and + lymphovascular space invasion. Also, as stage and grade of disease increased, CA-125 generally increased. The RR and OR tended to increase above a CA-125 threshold of 35U/ml for all participants. The participants who had a CA-125 level of 9 U/ml, 10 U/ml, or 12 U/ml had a decrease in risk of +lymph node metastasis 87%, 88%, and 72% respectively. With a CA-125 level of 222 U/ml or greater, the largest increase in risk for participants having stage II/III/IV disease was 52% greater than for stage I and the largest risk for those having stage III/IV disease was 66% greater. Participants with a CA-125 of 122 U/ml or greater showed a significantly increased risk of +lymph node metastasis and those with a CA-125 of 199 U/ml or greater showed a significantly increased risk of + lymphovascular space invasion. The authors concluded an elevated preoperative CA125 is associated with an increased risk of elevated stage, + lymphovascular space invasion, +lymph node metastasis, and higher grade, which could be associated with less favorable outcomes.

A 2026 retrospective analysis by Çaltek reported whether preoperative CA-125 and fibrinogen levels in those diagnosed with endometrial cancer can support preoperative risk assessment regarding surgical planning (particularly lymph node dissection), clinical staging, and need for adjuvant therapy. The primary outcome was lymph node metastasis with secondary outcomes including myometrial invasion of ≥ 50% and lymphovascular space invasion. With 582 individuals included, a total of 500 individuals underwent lymph node assessment. Lymph node metastasis was identified in 13.2% of individuals, myometrial invasion was identified in 37.3% of individuals, and lymphovascular space invasion was identified in 33.2% of individuals. This study has limitations including the single center and retrospective design which may have led to selection bias and limited generalizability. Despite these limitations, the study showed that preoperative CA-125 levels in those with endometrial cancer are associated with lymph node metastasis, myometrial invasion and lymphovascular space invasion which may assist with surgical planning and postoperative decisions.

Hereditary Breast and Ovarian Cancer

The 2026 NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate note that, in individuals with a hereditary syndrome that confers an increased lifetime risk of ovarian and breast cancer who have not undergone risk-reducing bilateral salpingo-oophorectomy, CA-125 surveillance using the Risk of Ovarian Cancer Algorithm (ROCA) has demonstrated a stage shift toward earlier detection of ovarian cancer. Conclusions were based on a study of 4348 individuals with an estimated lifetime ovarian cancer risk no less than 10% who underwent ovarian cancer screening via serum CA-125 tests every 4 months (using ROCA protocol). There were 13 participants who were diagnosed with ovarian cancer as a result of the screening protocol, with 5 of the 13 participants being diagnosed with early-stage cancer. The sensitivity, positive predictive value, and negative predictive value of the screening protocol for detecting ovarian cancer within 1 year were 94.7%, 10.8%, and 100%, respectively. The NCCN guidelines note it is appropriate to test for CA-125 for preoperative planning. The NCCN guidelines recommend testing of CA-125 for surveillance but do not provide specific recommendations for routine testing intervals.

The 2017 ACOG practice bulletin for Hereditary Breast and Ovarian Cancer Syndrome (ACOG, 2017) states:

In women with BRCA mutations or who have a personal or family history of ovarian cancer, routine ovarian cancer screening with measurement of serum CA 125 level or transvaginal ultrasonography generally is not recommended. Transvaginal ultrasonography or measurement of serum CA 125 level may be reasonable for short-term surveillance in women at high risk of ovarian cancer starting at age 30-35 years until the time they choose to pursue risk-reducing bilateral salpingo-oophorectomy.

Since there is an increased risk for ovarian cancer for those with BRCA mutations, Lentz and colleagues (2020) published results of prospective cohort study in which they used an algorithm which combined two biomarkers (CA-125 and HE4) for early detection of ovarian cancer in those individuals with BRCA mutations. Participants were enrolled into either a ROCA arm (n=149) or Standard of Care (SOC) surveillance (n=43). Surveillance in the ROCA arm was planned every 4 months while testing in the SOC arm was planned every 6 months. In the ROCA arm, abnormal scores of CA-125 results were 24%, 16% if CA-125 or HE4 was done independently, and 8% when both markers were used. In the SOC arm, abnormal test results were found in 15% of individuals. For those without ovarian cancer, for the two-marker ROCA referral to ultrasound, the average false positive rate was 6.6% (specificity 93.4%) and the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%).

Other Malignancies

Appendiceal adenocarcinoma is a rare type of cancer. Appendiceal cancer is frequently discovered incidentally during an appendectomy following clinical presentation of acute appendicitis. Management is based upon the classification, grade and stage of the neoplasm.

The 2026 NCCN Clinical Practice Guideline on Colon Cancer note that for appendiceal adenocarcinoma, CA-125 levels should be done, particularly if carcinoembryonic antigen (CEA) and CA 19-9 levels are normal. Also noting that normal CA-125 and CA19-9 levels correspond to an increase in survival and a decrease in recurrence of disease. The NCCN guidelines do not provide specific recommendations for routine testing intervals.

Expert review indicates CA-125 results can be clinically relevant in pancreatic adenocarcinoma, appendiceal adenocarcinoma, peritoneal mesothelioma and uterine neoplasms. The 2026 NCCN guideline for Pancreatic Adenocarcinoma notes that for resectable disease, neoadjuvant therapy, borderline resectable disease without metastases, and postoperative adjuvant treatment, CA-125 can be used in individuals who are nonsecreting or in those with normal CA 19-9 levels. The NCCN guidelines do not provide specific recommendations for routine testing intervals.

Peritoneal mesothelioma is a rare form of cancer that affects the peritoneum (the membrane that lines the abdominal cavity and organs). The use of paracentesis fluid (cytology) is not recommended for diagnosis as invasion can’t be detected using cytology. The 2026 NCCN guidelines for Mesothelial: Peritoneal recommends CA-125 could be considered for the initial evaluation of peritoneal mesothelial. The NCCN guidelines do not provide specific recommendations for routine testing intervals.

In the evaluation of uterine neoplasms, the 2026 NCCN guideline for Uterine Neoplasms recommends CA-125 in the initial preoperative evaluation for known or suspected malignancy, suspected extrauterine disease, and in surveillance of disease if the initial CA-125 was elevated. For those with extrauterine disease, CA-125 levels may be helpful to monitor clinical response. In addition, individuals with uterine serous carcinoma, clear cell carcinoma, carcinosarcoma, or undifferentiated/dedifferentiated carcinomas may present with pelvic masses, abnormal cervical cytology, or ascites in addition to postmenopausal bleeding. The NCCN also recommends CA-125 may be useful prior to surgery to assess if extrauterine disease is present. The NCCN guidelines do not provide specific recommendations for routine testing intervals.

Other Relevant Information

There is long-standing clearance of CA-125 assays by the U.S. Food and Drug Administration (FDA). The Vitros CA 125 II assay (Ortho-Clinical Diagnostics, Inc. K983875) and the ELECSYS CA 125 II assay (Boehringer Mannheim Corp., K972162) were cleared in 1998 for use as an aid for monitoring response to epithelial ovarian cancer therapy. Numerous NCCN guidelines recommend CA-125 testing in specific situations (see above for detailed discussion of these recommendations). The ACOG practice bulletins on evaluation and management of adnexal masses, and on hereditary breast and ovarian cancer syndrome recommend CA-125 testing in specific situations; ACOG does not recommend CA-125 tests for routine screening for ovarian cancer. National guidelines do not recommend CA-125 testing for screening or routine surveillance.

The CMS published NCD 190.28, titled, Tumor Antigen by Immunoassay - CA 125, which was effective on January 1, 2006. This document establishes when CA-125 testing is covered for Medicare enrollees.

Ascites: The accumulation of fluid in spaces within the abdomen.

Biomarker: A measurable indicator of a biological state or condition obtained from bodily fluids, such as blood or urine, or tissue samples. Biomarkers are used to diagnose diseases, monitor disease progression, predict disease prognosis, and track treatment response.

Carcinoembryonic antigen (CEA): A glycoprotein molecule that is associated with specific forms of cancer, particularly colorectal cancer. CEA may be used as a biomarker in diagnostic and prognostic evaluations.

Progression: Disease worsens or spreads without ever having gone away.

Recurrence: Cancer that has returned post treatment, often undetected for a certain period of time. Recurrence can happen at the same location as the initial tumor or at a different site in the body.

Screening Test: A test administered to individuals when there are no signs or symptoms of a specific condition.

Surveillance: It is used to detect early signs of recurrence in diseases, particularly cancer, or to monitor individuals at an increased risk of a disease.

Uterine neoplasm: A type of cancer which forms in the tissues of the uterus. Two types of uterine cancer are endometrial cancer (which begins in the cells lining the uterus) and uterine sarcoma (which begins in the muscle or other tissues in the uterus).

Peer Reviewed Publications:

1. Buys S, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial. JAMA. 2011; 305(22):2295-2303.
2. Çaltek NÇ, Yassa M, Şahin G,et al. Role of preoperative serum CA-125 and fibrinogen levels in predicting lymph node metastasis, myometrial invasion, and lymphovascular space invasion in patients with endometrial cancer. Eur J Obstet Gynecol Reprod Biol. 2026; 320:114985.
3. Einhorn N, Sjövall K, Knapp RC, et al. Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol. 1992; 80(1):14-18.
4. Jacobs IJ, Skates S, Davies AP, et al. Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study. BMJ. 1996; 313(7069):1355-1358.
5. Johnson CC, Kessel B, Riley TL, et al. The epidemiology of CA-125 in women without evidence of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial. Gynecol Oncol. 2008; 110(3):383-389.
6. Lentz SE, Powell CB, Haque R, et al. Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations. Gynecol Oncol. 2020; 159(3):804-810.
7. LyBarger K, Miller HA, Frieboes HB, et al. CA125 as a predictor of endometrial cancer lymphovascular space invasion and lymph node metastasis for risk stratification in the preoperative setting. Sci Rep. 2022; 12(1):19783.
8. Partridge E, Kreimer AR, Greenlee RT, et al. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol. 2009; 113(4):775-782.
9. Pinsky P, Yu K, Kramer B, et al. Extended mortality results for ovarian cancer screening in the PLCO trial with median 15 years follow-up. Gynecol Oncol. 2016; 143(2):270-275.
10. Yin C, Ethier JL, Carey MS, et al. Trajectories of cancer antigen 125 (CA125) within 3 and 6 months after the initiation of chemotherapy treatment for advanced ovarian cancer and clinical outcomes: a secondary analysis of data from a phase III clinical trial. Curr Oncol. 2025; 32(7):390.
11. Zurawski VR, Orjaseter H, Anderson A, et al. Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer. Int J Cancer. 1988; 42(5):677-680.

Government Agency, Medical Society, and Other Authoritative Publications:

1. ACOG Committee Opinion Number 716: The role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer in women at average risk. Obstet Gynecol. 2017 (re-affirmed 2024); 130(3):e146-e149.
2. ACOG Practice Bulletin No. 174: Evaluation and management of adnexal masses. Obstet Gynecol. 2016 (re-affirmed 2025); 128(5):e210-e226.
3. ACOG Practice Bulletin No. 182: Hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2017 (re-affirmed 2024); 130(3):e110-e126.
4. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination: Tumor antigen by immunoassay - CA 125. NCD# 190.28. Effective January 1, 2006. Available at: https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=130&ncdver=2. Accessed on June 9, 2026.
5. NCCN Clinical Practice Guidelines in Oncology^®. © 2026 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on June 9, 2026.
   • Colon Cancer (V2.2026). Revised April 7, 2026.
   • Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic and Prostate (V3.2026) Revised February 19, 2026.
   • Mesothelial: Peritoneal (V2.2026). Revised October 3, 2025.
   • Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer (V4.2026) Revised April 10, 2026.
   • Pancreatic Adenocarcinoma (V2.2026). Revised April 22, 2026.
   • Uterine Neoplasms (V2.2026). Revised November 14, 2025.
6. United States Preventive Services Task Force. Recommendation: Ovarian cancer. February 13, 2018. Available at: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/ovarian-cancer-screening. Accessed on June 9, 2026.
7. U.S. Food and Drug Administration. 510(k) Premarket Notification Database. Elecys CA 125 II Summary of Safety and Effectiveness. No. K972162. Rockville, MD: FDA. March 18, 1998. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf/K972162.pdf. Accessed on June 9, 2026.
8. U.S. Food and Drug Administration. 510(k) Premarket Notification Database. Vitros Immunodiagnostic Products CA-125 Assay Summary of Safety and Effectiveness. No. K983875. Rockville, MD: FDA. May 14, 1999. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf/K983875.pdf. Accessed on June 9, 2026.
9. Vanderpuye VD, Clemenceau JRV, Temin S, et al. Assessment of adult women with ovarian masses and treatment of epithelial ovarian cancer: ASCO resource-stratified guideline. JCO Glob Oncol. 2021; 7:1032-1066.

1. American Cancer Society. Ovarian cancer. Last revised August 8, 2025. Available at: https://www.cancer.org/cancer/types/ovarian-cancer.html. Accessed on June 9, 2026.
2. National Cancer Institute. Available at: https://www.cancer.gov/. Accessed on June 9, 2026.

CA-125

Federal and State law, as well as contract language, and Medical Policy take precedence over Clinical UM Guidelines. We reserve the right to review and update Clinical UM Guidelines periodically. Clinical guidelines approved by the Medical Policy & Technology Assessment Committee are available for general adoption by plans or lines of business for consistent review of the medical necessity of services related to the clinical guideline when the plan performs utilization review for the subject. Due to variances in utilization patterns, each plan may choose whether to adopt a particular Clinical UM Guideline. To determine if review is required for this Clinical UM Guideline, please contact the customer service number on the member's card.

Alternatively, commercial or FEP plans or lines of business which determine there is not a need to adopt the guideline to review services generally across all providers delivering services to Plan’s or line of business’s members may instead use the clinical guideline for provider education and/or to review the medical necessity of services for any provider who has been notified that his/her/its claims will be reviewed for medical necessity due to billing practices or claims that are not consistent with other providers, in terms of frequency or in some other manner.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

© CPT Only - American Medical Association