Serum Tumor Markers

Number 2.03.501*

Effective Date March 08, 2013

Revision Date(s) 03/08/13; 03/13/12; 09/13/11; 10/12/10; 03/10/09;04/08/08; 04/10/07; 05/09/06; 05/10/05; 03/30/04; 04/15/03; 05/14/02; 08/17/99; 06/01/99; 09/01/98; 05/05/97

Replaces 2.03.02

*Medicare has a policy.


Tumor Markers for Breast Cancer

The tumor markers listed below may be considered medically necessary for monitoring response to treatment and relapse for breast cancer:

  • CEA,
  • CA 15-3, and
  • CA 27-29.

The tumor markers listed below are considered investigational for screening asymptomatic subjects for breast cancer, for the differential diagnosis of breast cancer, and for monitoring the response to treatment:

  • CAM 26,
  • CAM 29,
  • MCA,
  • MSA,
  • TPA, and
  • the tumor marker that measures the antigen encoded by the MUC-1 gene (CA 549).

Tumor Markers for Colorectal, Gastric, or Pancreatic Cancer

The tumor markers listed below may be considered medically necessary for monitoring patients with colorectal, gastric, pancreatic or liver cancer:

  • CA 19-9,
  • CA 125, and
  • CEA.

Tumor Markers for Liver Cancer

The tumor markers listed below may be considered medically necessary for monitoring patients with liver cancer:

  • CA 19-9,
  • CA 125,
  • CEA and
  • AFP.

The tumor markers listed below are considered investigational for the diagnosis and monitoring of patients with colorectal, gastric, pancreatic or liver cancer:

  • CA 50,
  • CA 242,
  • CA 724, and
  • TPA.

Prostate-Specific Antigen (PSA)

Immunoassay of serum PSA is considered medically necessary for:

  • Monitoring response to treatment of prostate cancer when used for purposes of guiding patient management; and
  • For staging use in determining the need for a bone scan at the time of the initial diagnosis of prostate cancer. However, PSA is not sufficiently accurate to stage the extent of local disease for purposes of making a decision for radical prostatectomy.

Immunoassay of serum PSA is eligible for benefits for:

  • Screening asymptomatic men for prostatic disease; and
  • Differential diagnosis of patients with symptoms of prostatic disease.

Tumor Markers for Germ Cell or Testicular Cancer

The tumor markers listed below may be considered medically necessary for monitoring patients with germ cell or testicular cancer:

  • AFP, and
  • Beta HCG.

Tumor Markers for Ovarian Cancer

Measurement of CA 125 may be considered medically necessary for:

  • Monitoring patients with ovarian cancer;
  • Monitoring patients with known BRCA mutation; and
  • Premenopausal or postmenopausal women presenting with a complex adnexal mass suspicious of malignancy.

Chromogranin A (CgA)

CgA testing may be considered medically necessary for diagnosing and monitoring response to treatment for Carcinoid Syndrome and Neuroendocrine tumors.

Other Tumor Markers

Immunoassays of the following chemicals are considered investigational as tumor markers for screening asymptomatic subjects for cancer, for the differential diagnosis of cancer, and for monitoring the response to treatment:

  • A2-PAG, pregnancy-associated alpha-2 glycoprotein;
  • BCM, breast cancer mucin;
  • CA 50, cancer antigen 50;
  • CA 72-4, cancer antigen 72-4;
  • CA 195, cancer antigen 195;
  • CA 242, cancer antigen 242;
  • CA 549, carbohydrate antigen/cancer antigen 549;
  • CA SCC, squamous cell carcinoma antigen;
  • CAM 17-1, monoclonal antimucin antibody 17-1;
  • CAM 26, monoclonal antimucin antibody 26;
  • CAM 29, monoclonal antimucin antibody 29;
  • CAR-3 - antigenic determinant recognized by monoclonal antibody AR-3
  • DU-PAN-2, sialylated carbohydrate antigen DU-PAN-2;
  • MCA, mucin-like carcinoma-associated antigen;
  • MSA, mammary serum antigen;
  • NSE, neuron-specific enolase;
  • P-LAP, placental alkaline phosphatase;
  • PNA/ELLA, peanut lectin bonding assay;
  • SLEX, sialylated Lewis X-I antigen;
  • SLX, sialylated SSEA-1 antigen;
  • SPAN-1, sialylated carbohydrate antigen SPAN-1;
  • ST-439, sialylated carbohydrate antigen ST-439;
  • TAG12, tumor-associated glycoprotein 12;
  • TAG72, tumor-associated glycoprotein 72
  • TAG72.3, tumor-associated glycoprotein 72.3;
  • TATI, tumor-associated trypsin inhibitor;
  • TNF-a, tumor necrosis factor alpha; and
  • TPA, tissue polyleptic antigen.

Related Policies


Urinary Tumor Markers for Bladder Cancer


Proteomics-based testing for the Evaluation of Ovarian (Adnexal) Masses


Serum Biomarker Human Epididymis Protein 4 (HE4)

Policy Guidelines



Serum tumor markers are molecules or substances that are shed by a tumor into the circulation where they can be detected and quantitated. Noncirculating tumor markers include those that can be detected histologically on a tissue sample, or even cytogenetically. An example of the latter includes the Philadelphia chromosome, which is a cytogenetic marker for chronic myelogenous leukemia.

Serum tumor markers have been investigated in a wide variety of malignancies, including most prominently myeloma (i.e., beta-2 microglobulin), germ cell tumors (i.e., alpha-feto-protein, human chorionic gonadotropin), and prostate cancer (i.e., PSA). Carcinoembryonic antigen (CEA) has also been widely investigated in gastrointestinal malignancies. All of the above circulating tumor antigens have their own specific CPT codes and are not addressed by this policy.

For breast cancer, the most extensively investigated tumor markers are those associated with the MUC-1 gene. For gastrointestinal cancer, including gastric, pancreatic, and colorectal cancer, the most extensively studied tumor markers other than CEA are those related to mucinous glycoproteins. The MUC-1 gene encodes a cell-associated mucin-like antigen, and different antibodies may be used to detect different epitopes. CA 15-3 and CA 27.29 are two related monoclonal antibodies that detect antigens encoded by the MUC-1 gene. While much of the literature has focused on the use of CA 15-2, this tumor marker has been largely replaced by CA 27.29, which is considered more sensitive. The mucinous glycoproteins of the gastrointestinal tract include CA 19-9, CA 242, and CA 72-4, again depending on which antibody is used. Other serum tumor markers that have been less extensively investigated include tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS), both epitopes of cytokeratin, a marker of epithelial cells.

Ovarian Cancer

Human epididymis protein 4 (HE4) is a potential new biomarker for detecting ovarian cancer early and for monitoring disease progression and recurrence. It has been cleared by the U.S. Food and Drug Administration (FDA) for monitoring patients with epithelial ovarian cancer. HE4 is proposed as a replacement for, or complement to, CA 125 a biomarker with limited specificity.

Stage at diagnosis is an important predictor of survival; however, most women are not diagnosed until the disease has spread. According to Surveillance Epidemiology and End Results (SEER) data, for the period 1999-2006, 62% of women with ovarian cancer were diagnosed when the disease had distant metastases (Stage IV) and this was associated with a 27.6% five-year survival rate. In contrast, the 15% of women diagnosed with localized cancer (Stage I) had a 93.5% five-year survival rate. (2) Epithelial ovarian tumors account for 85-90% of ovarian cancers.

Several factors contribute to the frequent late-stage diagnosis of ovarian cancer. First, symptoms are non-specific (e.g., abdominal pain, persistent indigestion and bloating, urinary urgency, fatigue and weight loss) and many women do not immediately seek medical consultation. When women seek care, doctors frequently do not recognize the implications of the symptoms and diagnosis can be delayed. Furthermore, there is no reliable test to differentiate between benign and malignant pelvic masses. Generally, women are evaluated with a pelvic examination and ultrasound, and if they are found to have a pelvic mass, they are referred for surgery. The standard treatment for epithelial ovarian cancer is surgical staging and primary cytoreductive surgery followed by chemotherapy in most cases. Health outcomes tend to be better for women with ovarian cancer who are treated by gynecologic oncologists. The proteomics-based OVA1 is cleared by the FDA for assessing the likelihood of malignancy in women with adnexal masses. Following treatment for ovarian cancer, women continue to be monitored for disease recurrence.

In addition to the tests and procedure discussed above, there is interest in identifying biomarkers that can be used to manage patients with ovarian cancer. Currently, the most widely used biomarker is CA-125, a high-molecular-weight protein antigen. Testing for CA 125 in women with a pelvic mass suggestive of ovarian cancer is common practice. However, although elevated serum CA 125 levels are highly correlated with epithelial ovarian cancer (elevated in about 80% of cases), levels can also be elevated by benign gynecological and medical conditions such as endometriosis, congestive heart failure and cirrhosis, limiting the specificity for distinguishing between benign and malignant masses. Moreover, CA 125 levels tend to be higher in pre-menopausal women, increasing the likelihood of false-positives when used in this population. After treatment for ovarian cancer, serial measurement of CA 125 has been used to detect early recurrence of disease. A rising CA 125 level has been found to correlate with disease recurrence, although a survival advantage of detecting recurrence early with CA 125 compared to symptomatic detection has not yet been demonstrated.

Another serum biomarker, recently cleared by the FDA for monitoring patients with epithelial ovarian cancer, HE4, which is made up of two whey acidic proteins with a four disulfide core domain. It has been found to be over-expressed by epithelial ovarian cancer tumors and to circulate in the serum of patients with epithelial ovarian cancer. Levels of HE4 may be less likely to be elevated due to benign conditions, as is the case with CA 125, which would make it a candidate to replace or complement CA 125. See policy 12.04.66 Serum Biomarker Human Epididymis Protein 4 (HE4). (See Related Policies)

Since serum tumor markers can also be detected in normal or benign lesions, significant circulating levels are associated with malignancy due to one or more of the following mechanisms: 1) overexpression of the antigen by individual malignant cells; 2) a large tumor burden; and/or 3) the clearance rate of the marker. For example, since most tumor markers are cleared by the liver, liver abnormalities (whether benign, malignant, or inflammatory) may be associated with elevated tumor markers due to impaired clearance. Because most tumor markers are not unique to malignancy, cut-off points for what is considered a normal or abnormal level of tissue markers must be established. Alternatively, serial monitoring of serum tumor markers in a setting of established malignancy may not require such cut-off points. Various clinical applications of serum tumor markers can be broadly divided into two categories, those involving a single measurement of the serum tumor marker and those involving serial measurements.

Single Measurement of Serum Tumor Markers


Diagnosis of a suspected malignancy or unknown primary requires a tumor marker that is relatively specific for a given tumor. Since most tumor markers, including those discussed above, are expressed both in normal, benign conditions and by malignancies, serum tumor markers are rarely used for diagnosis. Exceptions include human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP), whose elevated levels are both consistently seen with germ cell tumors. In addition, markedly elevated PSA is highly suggestive of a prostatic malignancy.


A key determinant of initial therapy of epithelial tumors is to determine their surgical resectability; the presence of distant metastases generally excludes surgical resectability. Therefore, the presence of elevated tumor markers (whose levels are related to tumor burden) may suggest metastatic disease not otherwise detected by routine clinical exam and prompt a more vigorous search for metastatic disease prior to surgery. For example, markedly elevated levels of PSA are highly suggestive of metastatic prostate cancer.

Serial Monitoring of Serum Tumor Markers

Monitoring Response to Therapy

Response to systemic therapy, whether hormonal or cytotoxic, may be reflected by decreasing levels of serum tumor markers. In this setting, the value of an individual tumor marker and whether it represents positive or negative relative to an arbitrarily defined cut-off is not as important as the trend analysis observed in serial monitoring. Interpretation of trends in tumor markers will depend on an understanding of the normal biologic variation of tumor markers as well as the analytic variation.

Monitoring for Recurrence

Patients who are no longer receiving therapy may be monitored for recurrence as evidenced by increasing tumor markers detected in serial monitoring. For example, serial monitoring of PSA in patients with a history of prostate cancer and CA 125 in patients with ovarian cancer are common examples. The limitations of interpretation are similar to those described for monitoring therapy response, described above. In patients with a history of breast or gastrointestinal malignancy, serial monitoring for recurrence using serum tumor markers related to the MUC-1 gene (breast) or mucinous glycoproteins (gastrointestinal) has been the application most widely studied.

The clinical applicability of serum tumor markers will ultimately depend on how their measurement may be used to influence the management of the patients and whether these management changes will result in an improvement in patient outcome.

At the present time, no known molecular or cytogenic tumor marker has been identified to help diagnose, manage or confirm renal cell carcinoma remission, progression or relapse.


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Benefit Application



2006 Update

Sasaki and colleagues noted that carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are frequently elevated in patients with colorectal carcinoma. However, the predictive utility of these two markers has not been fully investigated in patients with liver metastasis. Sasaki retrospectively analyzed data from 90 hepatectomy or non-hepatectomy patients with liver metastases from colorectal. They concluded that in patients with colorectal liver metastasis, elevation of serum CA 19-9 is a risk factor for extrahepatic metastasis and CEA appears to be useless for predicting extrahepatic metastasis in these patients.

Duffy studied CA 15-3 and CEA which are the most widely used serum based tumor markers for breast cancer. Systematic reviews, prospective randomized trials and guidelines issued by expert panels were reviewed. This study indicates one of the first circulating prognostic factors for breast cancer is CA 15-3. Preoperative concentrations might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At the present time, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer.

2008 Update

The National Comprehensive Cancer Network (NCCN) Practice Guidelines for Hereditary Breast and/or Ovarian Cancer recommends the use of concurrent transvaginal ultrasound plus CA 125 for those who have not elected risk reducing surgery following breast cancer.

Dearking and colleagues evaluated the referral guidelines published by American College of Obstetricians and Gynecologists (ACOG) and Society of Gynecologic Oncologists (SGO), which provide guidance about when to refer a patient with a pelvic mass to a gynecologic oncologist. Data from consecutive patients evaluated for pelvic mass were collected prospectively over a five-year period. Eight hundred thirty-seven patients met inclusion criteria. Forty-four percent (263/597) of postmenopausal women were diagnosed with ovarian cancer, whereas 20% (48/240) of premenopausal women had ovarian cancer. Seventy-four percent of primary cancers were stage III or IV. The referral guidelines were 79.2% sensitive and 69.8% specific for premenopausal women, with a positive predictive value of 39.6%. For postmenopausal women, the guidelines were 93.2% sensitive and 59.9% specific, and positive predictive value was 64.6%. The referral guidelines performed better for late-stage than early-stage cancers in both sensitivity and positive predictive value, especially in postmenopausal women. Lowering the CA 125 cutoff level required for referral of premenopausal patients increased the sensitivity of the guidelines in their group. They concluded that the ACOG/SGO guidelines perform well in predicting advanced-stage ovarian cancer, probably owing to the nature of advanced-stage disease. The guidelines perform poorly in identifying early-stage disease, especially in premenopausal women, primarily due to lack of early markers and signs of ovarian cancer. They recommend the referral guidelines be revised to exclude family history of breast or ovarian cancer and lowering the CA 125 referral level for premenopausal women to more than 67 units/mL.

2009 Update

The chromogranin A (CgA) blood test measures a protein found in tumor cells such as carcinoid and neuroendocrine tumors. The NCCN Practice Guidelines in Oncology v.1.2008 for Neuroendocrine Tumors lists CgA as a laboratory study that is basic for the work-up of Neuroendocrine Tumors.

2010 Update

NSE for Non-small Cell Lung Cancer

Neuron-specific enolase (NSE) studies have concentrated primarily on patients with non-small cell lung cancer. However, studies indicate that NSE cannot be used to monitor response to treatment because of the poor sensitivity of this marker. Current NCCN Clinical Practice Guidelines in Oncology (Non-small Cell Lung Cancer, V.2.2013) do not address the use of NSE in the management of non-small lung cancer patients. Therefore it remains investigational.

2011 Update

National Comprehensive Cancer Network (NCCN) Guidelines

2011 NCCN guidelines for pancreatic adenocarcinoma (v2.2011) recommend measurement of serum CA 19-9 level following surgery prior to administration of adjuvant therapy (pretreatment baseline assessment following surgery) to evaluate for the presence of metastatic disease before adjuvant chemoradiation is initiated. As a category 2B recommendation, the guidelines recommend CA 19-9 determinations and follow-up computed tomography (CT) scans every 3 to 6 months for 2 years after surgical resection because data are not available to show that earlier treatment of recurrences, following detection by increased tumor marker levels or CT scan, leads to better patient outcomes.

2011 NCCN guidelines for colon cancer (v3.2011) recommend CEA testing as a part of the workup for colon cancer.

Technology Assessments, Guidelines and Position Statements

The 2010 National Comprehensive Care Network (NCCN) ovarian cancer guideline recommends testing for CA 125 or other tumor markers as clinically indicated as part of the initial workup for ovarian cancer and for monitoring response to treatment. They do not include any specific recommendations on HE4 testing.

Information from older technology assessments and guidelines are listed below. These will be re-examined in future updates of the policy:

  • In 2007, the American College of Obstetricians and Gynecologists issued a guideline on the management of adnexal masses. The guideline included a statement that specificity and positive predictive value of CA 125 level measurements are higher in post-menopausal women compared to pre-menopausal women. No recommendations on use of the HE4 biomarker were included.
  • In 2006, the Duke University Evidence-based Practice Center, under contract to the Agency for Healthcare Research and Quality (AHRQ), published a technology assessment on genomic tests for ovarian cancer detection and management. HE4 was mentioned only in terms of the analytic validity of available tests. Among the conclusions of the review was the statement that:

“There are almost no data on the sensitivity and specificity of genomic tests for screening or diagnosis in clinically realistic settings. Although results of some genomic tests have been shown to be associated with certain outcomes of treatment, there are no data on how changes in management based on those test results would lead to improved patient outcomes.”

2013 Update

The 2012 National Comprehensive Care Network (NCCN) prostate cancer detection guideline regarding PSA testing recommends starting a “risks and benefits discussion about offering baseline digital rectal exam and PSA at age 40.”However, NCCN states: “It is neither the intent nor the suggestion of the panel that all men diagnosed with prostate cancer require treatment. It is inherent that as we maximize the detection of early prostate cancer we will increase the detection of non-aggressive (slow-growing) and aggressive (faster growing) prostate cancers. The challenge is to identify the biology of the cancer that is detected and thus identify cancers that, if treated effectively, will result in a significant decrease in morbidity and mortality.”

Information regarding serum biomarker human epididymis protein 4(HE4) was removed from this policy and moved to a singular policy addressing this biomarker.


  1. Mejean A. Prognostic factors of renal cell carcinoma. Journal of Urology, 2003; 169(3):821-7.
  2. Smith TJ, Davidson NE, Schapira DV et al. American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines. J Clin Oncol 1999; 17(3):1080-2.
  3. Bast RC, Ravdin P, Hayes DF et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001; 19(6):1865-78.
  4. Rocha Lima CM, Savarese D, Bruckner H et al. Irinotecan plus gemcitabine induce both radiographic and CA 19-9 tumor marker responses in patients with previously untreated pancreatic cancer. J Clin Oncol 2002; 20(5):1182-91.
  5. Allard WJ, Matera J, Miller MC et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Re. 2004;10(20):6897-6901.
  6. 2005 Update of ASCO Practice Guideline Recommendations for Colorectal Cancer Surveillance: Guideline Summary. Amer Soc of Clinical Oncol; 2005.
  7. 2000 Update of ASCO Recommendations for the Use of Tumor Markers in Breast and Colorectal Cancer: Clinical Practice Guidelines of the American Society of Clinical Oncology. J Clin Oncol; 2001:1865-1878.
  8. Sasaki A, Kawano K, Inomata M et al. Value of serum carbohydrate antigen 19-9 for predicting extrahepatic metastasis in patients with liver metastasis from colorectal carcinoma. Hepatogast 2005; 52(66):1814-9.
  9. Duffy MJ. Serum tumor markers in breast cancer: are they of clinical value? Clin Chem 2006; 52(3):345-51.
  10. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer (V.1.2012). Last accessed January 21, 2013.
  11. Dearking AC, Aletti GD et al. How Relevant are ACOT and SGO Guidelines for Referral of Adnexal Mass? Obstet Gynecol. 2007 Oct;110(4):841-8.
  12. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Neuroendocrine Tumors (V.1.2012). Last accessed January 21, 2013.
  13. Policy reviewed and recommended for adoption by the Oncology Advisory Panel, February 22, 2007; February 21, 2008; February 19, 2009.
  14. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. (V.2.2013). Last accessed January 21, 2013.
  15. Jemal A, Siegel R, Xu J et al. Cancer Statistics, 2010. CA Cancer J Clin 2010 July 7 [Epub ahead of print].
  16. National Cancer Institute. Surveillance, Epidemiology and End Results (SEER). SEER Stat Fact Sheets: Ovary. Last accessed January 21, 2013.
  17. U.S. Food & Drug Administration (FDA). 510(k) k072939: substantial equivalence determination decision summary: assay only. Last accessed January 21, 2013.
  18. U.S. Food & Drug Administration (FDA). 510(k) k093957: substantial equivalence determination decision summary: assay only. Last accessed January 21, 2013.
  19. Moore RG, Brown AK, Miller MC et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol 2008; 108(2):402-8.
  20. Nolen B, Velikokhatnaya L, Marrangoni A et al. Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol 2010; 117(3):440-5.378-83.
  21. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Colon Cancer. V.3.2013. Last accessed January 21, 2013.
  22. American College of Obstetricians and Gynecologists (ACOG). Management of adnexal masses. Washington DC: 2007 (ACOG practice bulletin; no. 83). Last accessed January 21, 2013.
  23. Myers ER, Havrilesky LJ, Kulasingham SL et al. Genomic tests for ovarian cancer detection and management. Prepared by Duke University Evidence-based Practice Center for Agency for Healthcare Research and Quality. AHRQ Publication No. 07-E001. October 2006. Last accessed January 21, 2013.
  24. Reviewed and recommended by the Premera Oncology Advisory Panel February 2011; February 16, 2012.
  25. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma (V.2.2012). Last accessed January 21, 2013.
  26. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Prostate Cancer Early Detection. (V.2.2012). Last accessed February 24, 2013.







Prostate-specific antigen (PSA); total



Immunoassay for tumor antigen, quantitative; CA15-3 (27.29)






CA 125



Immunoassay for tumor antigen, other antigen, quantitative (e.g., CA50, 72-4, 549), each

ICD-9 Procedure


ICD-9 Diagnosis


Malignant neoplasm of stomach, cardia






Pyloric antrum



Fundus of stomach



Body of stomach



Lesser curvature, unspecified



Greater curvature, unspecified



Other specified sites of stomach



Stomach, unspecified



Malignant neoplasm of colon, hepatic flexure



Transverse colon



Descending colon



Sigmoid colon









Ascending colon



Splenic flexure



Other specified sites of large intestine



Colon, unspecified



Malignant neoplasm of rectum, rectosigmoid junction, and anus, rectosigmoid junction






Anal canal



Anus, unspecified






Malignant neoplasm of pancreas, head of pancreas



Body of pancreas



Tail of pancreas



Pancreatic duct



Islets of Langerhans



Other specified sites of pancreas



Pancreas, part unspecified



Malignant neoplasm of female breast, nipple and areola



Central portion



Upper-inner quadrant



Lower-inner quadrant



Upper-outer quadrant



Lower-outer quadrant



Axillary tail



Other specified sites of female breast



Breast (female), unspecified



Malignant neoplasm of male breast, nipple and areola



Other and unspecified sites of male breast






Fallopian tube



Broad ligament






Round ligament



Other specified sites of uterine adnexa



Uterine adnexa, unspecified



Type of Service



Place of Service


Physician’s Office








Add to Medicine Section - New Policy


Replace Policy - Policy reviewed


Replace Policy - Indications changed


Replace Policy - Added reference to ovarian and breast cancer to Item 2 in Policy section.


Replace Policy - Policy updated with no policy statement changes.


Replace Policy - Policy updated with no policy statement changes. Added info in description section about renal cell carcinoma. Updated references and codes.


Replace Policy - Policy updated with no policy statement changes.


Replace Policy - Policy renumbered from 2.03.101. No changes to dates.


Replace Policy - Policy reviewed; tumor markers added to policy statement. Serum added to title to differentiate from tissue.


Replace Policy - Policy reviewed with literature search; references updated; no change in policy statement.


Update Scope and Disclaimer - No other changes.


Replace Policy - Policy updated with literature review; no change to policy statement. References added and codes updated. Policy reviewed and recommended by OAP February 22, 2007.


Cross Reference Update - No other changes.


Replace Policy - Policy updated with literature search. Policy statement to include “Measurement of CA 125” as medically necessary in monitoring with known BRCA mutation. Policy reviewed and recommended for adoption by the Oncology Advisory Panel, February 21, 2008.


Cross Reference Update - No other changes.


Replace Policy - Policy updated with literature search. Policy statement updated to include Chromogranin A indication per request from OAP. Reference added. Reviewed by OAP February 19, 2009.


Replace Policy - Policy updated with literature search. HE4, previously not addressed, is considered investigational for ovarian cancer. Rationale and References added.


Replace Policy – Policy updated with literature search. Rationale and References added. No change to the policy statement.


Replace Policy – Policy updated with literature search. Rationale and References added. No change to the policy statement. Reviewed and recommended by OAP on February 16, 2012.


Update Related Policy – Remove 2.01.45 as it was archived.


Update Related Policies - Add 12.04.66.


Replace policy. Policy updated with literature search. Rationale updated; references removed, added and renumbered. Statement on HE4 as investigational removed because it is addressed as investigational in 12.04.66 Serum Biomarker Human Epididymis Protein 4 (HE4). No change to the policy statement other than minor reformatting consolidating two statements on liver cancer. CPT code 86305 removed, as this relates to HE4.


Update Related Policies. Remove policy 2.04.34 as it was archived.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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