Gene Expression Profiling for Cancers of Unknown Primary Site

Medical Policy

Gene Expression Profiling for Cancers of

Unknown Primary Site

Policy Number: PG0364

Last Review: 06/01/2024

_

GUIDELINES:

? This policy does not certify benefits or authorization of benefits, which is designated by each individual

policyholder terms, conditions, exclusions, and limitations contract. It does not constitute a contract or

guarantee regarding coverage or reimbursement/payment. Self-Insured group specific policy will supersede

this general policy when group supplementary plan document or individual plan decision directs otherwise.

? Paramount applies coding edits to all medical claims through coding logic software to evaluate the accuracy

and adherence to accepted national standards.

? This medical policy is solely for guiding medical necessity and explaining correct procedure reporting used to

assist in making coverage decisions and administering benefits.

SCOPE:

X Professional

X Facility

DESCRIPTION:

Gene expression profiling (GEP) is a laboratory test that measures the activity, or expression, of ribonucleic acid

(RNA) of hundreds to thousands of genes at one time to give an overall picture of gene activity. GEP tests are

typically performed on tumor tissue but may also be performed on other specimens such as blood. GEP tests

are currently offered primarily for the management of cancer, including breast, colon, cancer of unknown primary

(CUP) site, cutaneous (skin) melanoma, hematologic malignancies, lung, oral cancer, squamous cell cancer,

urothelial (bladder) and uveal melanoma.

Cancers of unknown primary (CUP) site, also referred as tumor of unknown origin (TOO), are tumors that have

metastasized from an unknown primary source; they make up approximately 3% of all cancer cases in the U.S.

The premise of tissue of origin testing in CUPs is that identifying a likely primary tumor site will provide informed

treatment selection leading to improved survival and other outcomes.

The CancerTYPE ID is a real-time reverse transcription PCR (RT-PCR) profiling test that compares the RNA

expression from formalin-fixed paraffin-embedded (FFPE) tumor tissue from a patient with cancer of unknown

primary (CUP) to the expression patterns of a panel of 50 different tumor types and subtypes to identify the most

likely primary tissue of origin. There is insufficient evidence to assess the clinical utility of the CancerTYPE ID,

and limited evidence to assess its analytical and clinical validity in patients with cancer of uncertain primary to

identify the most likely primary tissue of origin.

The Tissue of Origin Test is a microarray-based RNA profiling test that compares the RNA expression of

formalin-fixed paraffin-embedded (FFPE) tumor tissue from a patient with CUP to the expression patterns of a

panel of 15 known characterized tumor types (bladder, breast, colorectal, gastric, hepatocellular, kidney,

melanoma, non-Hodgkin¡¯s lymphoma, non-small cell lung, ovarian, pancreas, prostate, sarcoma, testicular germ

cell, and thyroid) to identify the most likely primary tissue of origin.

ProOnc TumorSourceDX uses miRview mets technology to identify tissue of origin for a metastatic tumor. RNA

is extracted from samples of FFPE tumor sections of unknown primary origin. Developmental origin of tumor is

determined using microarray-based miRNA expression profiling and a decision tree classification algorithm. The

patient population that may be considered for miRview mets testing includes patients with CUP to diagnosis

primary origin. In addition, patients with carcinomas of suspected or known primary origin may be considered for

PG0364-03/11/2024

Page 1 of 8

miRview mets testing to confirm diagnosis.

The RosettaGX Reveal test is a quantitative reverse transcription PCR (qRT-PCR)-based profiling test that

measures microRNA expression levels in RNA extracted from stained thyroid fine-needle aspiration (FNA)

biopsy smears or cell blocks. A proprietary algorithm classifier combines linear discriminant analysis steps and a

K Nearest Neighbor classifier step to differentiate thyroid nodules as benign or suspicious for malignancy. In

addition, the test measures the hsa-miR-375 marker for medullary carcinoma.

To date, most of the available studies fail to provide sufficient evidence that gene expression profiling to identify

the tissue of origin for cancers lead to improved health outcomes (i.e., clinical utility). Well-designed randomized

controlled trials (RCTs) are needed to determine the clinical utility of gene expression profiling to identify the

tissue of origin for cancers of unknown primary site compared with traditional clinicopathologic factors to guide

medical management and improve clinical outcomes.

POLICY:

Paramount Commercial Plans

Gene expression profiling to identify the tissue of origin for cancers of unknown primary site (81504,

81540) is non-covered, including but not limited to:

? CancerTYPE ID

? ResponseDX Tissue of Origin Test

? ProOnc TumorSourceDX

? RosettaGX Cancer Origin

Elite (Medicare Advantage) Plans

? CancerTYPE ID (81540) does not require prior authorization.

? ResponseDX Tissue of Origin Test (81504) does not require prior authorization.

? All other tests for gene expression profiling to identify the tissue of origin for cancers of unknown

primary site are non-covered, including but not limited to:

o ProOnc TumorSourceDX

o RosettaGX Cancer Origin

COVERAGE CRITERIA:

Paramount Commercial Insurance Plans

Gene expression profiling is considered experimental/investigational and not medically necessary as a technique

to identify the tissue of origin for cancers of unknown primary site for all indications, including but not limited to:

? Determining the tissue of origin for a primary tumor; or

? Determining the tissue of origin for a metastatic tumor.

Elite (Medicare Advantage) Plans

While there is insufficient evidence in the published medical literature to demonstrate the safety, efficacy, and

long-term outcomes of CancerTYPE ID, CMS requires this test be covered for Medicare Advantage Plan

members with cancer of unknown primary (CUP) site.

To bill for CANCER TYPE ID, please provide the following claim information:

? For services use CPT code 81540

? Enter ¡°1¡± in the Days/Unit field

? Select the appropriate ICD-10-CM code as listed below (ICD-10 CODES THAT ARE

COVERED FOR CANCER TYPE ID FOR Elite (Medicare Advantage) Plan ONLY

While there is insufficient evidence in the published medical literature to demonstrate the safety, efficacy and

long-term outcomes of ResponseDX Tissue of Origin Test, CMS requires this test be covered for Medicare

Advantage Plan members with cancer of unknown primary (CUP) site.

To bill for ResponseDX Tissue of Origin Test, please provide the following claim information:

PG0364-03/11/2024

Page 2 of 8

?

?

?

For services use CPT code 81504

Enter ¡°1¡± in the Days/Unit field

Select the appropriate ICD-10-CM code as listed below (ICD-10 CODES THAT ARE

COVERED FOR RESPONSEDX TISSUE OF ORIGIN FOR Elite (Medicare Advantage) Plan

ONLY

Paramount expects these tests to ONLY be ordered by the treating physician.

CODING/BILLING INFORMATION:

The appearance of a code in this section does not necessarily indicate coverage. Codes that are covered

may have selection criteria that must be met. Payment for supplies may be included in payment for other

services rendered.

CPT CODES

Oncology (tissue of origin), microarray gene expression profiling of > 2000 genes, utilizing formalin81504

fixed paraffin-embedded tissue, algorithm reported as tissue similarity scores

Oncology (tumor of unknown origin), mRNA, gene expression profiling by real-time RT-PCR of 92

genes (87 content and 5 housekeeping) to classify tumor into main cancer type and subtype,

81540

utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a probability of a predicted

main cancer type and subtype

ICD-10 CODES THAT ARE COVERED FOR CANCERTYPE ID FOR Elite (Medicare Advantage) Plans

ONLY

C18.1

Malignant neoplasm of appendix

C18.9

C22.0

C22.2

C22.3

C22.4

C22.7

C22.8

C22.9

C25.2

C25.7

C25.8

C25.9

C33

C34.01

C34.02

C34.11

C34.12

C34.2

C34.31

C34.32

C34.81

C34.82

C34.91

C34.92

C43.51

C43.52

C43.59

C45.9

C47.0

C47.9

C48.0

Malignant neoplasm of colon, unspecified

Liver cell carcinoma

Hepatoblastoma

Angiosarcoma of liver

Other sarcomas of liver

Other specified carcinomas of liver

Malignant neoplasm of liver, primary, unspecified as to type

Malignant neoplasm of liver, not specified as primary or secondary

Malignant neoplasm of tail of pancreas

Malignant neoplasm of other parts of pancreas

Malignant neoplasm of overlapping sites of pancreas

Malignant neoplasm of pancreas, unspecified

Malignant neoplasm of trachea

Malignant neoplasm of right main bronchus

Malignant neoplasm of left main bronchus

Malignant neoplasm of upper lobe, right bronchus or lung

Malignant neoplasm of upper lobe, left bronchus or lung

Malignant neoplasm of middle lobe, bronchus or lung

Malignant neoplasm of lower lobe, right bronchus or lung

Malignant neoplasm of lower lobe, left bronchus or lung

Malignant neoplasm of overlapping sites of right bronchus and lung

Malignant neoplasm of overlapping sites of left bronchus and lung

Malignant neoplasm of unspecified part of right bronchus or lung

Malignant neoplasm of unspecified part of left bronchus or lung

Malignant melanoma of anal skin

Malignant melanoma of skin of breast

Malignant melanoma of other part of trunk

Mesothelioma, unspecified

Malignant neoplasm of peripheral nerves of head, face and neck

Malignant neoplasm of peripheral nerves and autonomic nervous system, unspecified

Malignant neoplasm of retroperitoneum

PG0364-03/11/2024

Page 3 of 8

C49.0

C49.9

C50.411

C50.412

C50.511

C50.512

C50.811

C50.812

C50.911

C50.912

C56.1

C56.2

C61

C64.1

C64.2

C67.5

C67.9

C76.0

C77.0

C77.1

C77.2

C77.3

C77.4

C77.5

C77.8

C77.9

C78.01

C78.02

C78.5

C78.6

C78.7

C79.01

C79.02

C79.2

C79.31

C79.49

C79.51

C79.52

C79.61

C79.62

C79.89

C80.0

C80.1

C82.57

C84.A7

C84.Z7

C84.97

C85.17

C85.27

C85.87

C85.97

C86.1

Malignant neoplasm of connective and soft tissue of head, face and neck

Malignant neoplasm of connective and soft tissue, unspecified

Malignant neoplasm of upper-outer quadrant of right female breast

Malignant neoplasm of upper-outer quadrant of left female breast

Malignant neoplasm of lower-outer quadrant of right female breast

Malignant neoplasm of lower-outer quadrant of left female breast

Malignant neoplasm of overlapping sites of right female breast

Malignant neoplasm of overlapping sites of left female breast

Malignant neoplasm of unspecified site of right female breast

Malignant neoplasm of unspecified site of left female breast

Malignant neoplasm of right ovary

Malignant neoplasm of left ovary

Malignant neoplasm of prostate

Malignant neoplasm of right kidney, except renal pelvis

Malignant neoplasm of left kidney, except renal pelvis

Malignant neoplasm of bladder neck

Malignant neoplasm of bladder, unspecified

Malignant neoplasm of head, face and neck

Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck

Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes

Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes

Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes

Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes

Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes

Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions

Secondary and unspecified malignant neoplasm of lymph node, unspecified

Secondary malignant neoplasm of right lung

Secondary malignant neoplasm of left lung

Secondary malignant neoplasm of large intestine and rectum

Secondary malignant neoplasm of retroperitoneum and peritoneum

Secondary malignant neoplasm of liver and intrahepatic bile duct

Secondary malignant neoplasm of right kidney and renal pelvis

Secondary malignant neoplasm of left kidney and renal pelvis

Secondary malignant neoplasm of skin

Secondary malignant neoplasm of brain

Secondary malignant neoplasm of other parts of nervous system

Secondary malignant neoplasm of bone

Secondary malignant neoplasm of bone marrow

Secondary malignant neoplasm of right ovary

Secondary malignant neoplasm of left ovary

Secondary malignant neoplasm of other specified sites

Disseminated malignant neoplasm, unspecified

Malignant (primary) neoplasm, unspecified

Diffuse follicle center lymphoma, spleen

Cutaneous T-cell lymphoma, unspecified, spleen

Other mature T/NK-cell lymphomas, spleen

Mature T/NK-cell lymphomas, unspecified, spleen

Unspecified B-cell lymphoma, spleen

Mediastinal (thymic) large B-cell lymphoma, spleen

Other specified types of non-Hodgkin lymphoma, spleen

Non-Hodgkin lymphoma, unspecified, spleen

Hepatosplenic T-cell lymphoma

PG0364-03/11/2024

Page 4 of 8

D01.5

Carcinoma in situ of liver, gallbladder and bile ducts

D01.7

Carcinoma in situ of other specified digestive organs

D01.9

Carcinoma in situ of digestive organ, unspecified

D02.21

Carcinoma in situ of right bronchus and lung

D02.22

Carcinoma in situ of left bronchus and lung

D03.51

Melanoma in situ of anal skin

D03.52

Melanoma in situ of breast (skin) (soft tissue)

D03.59

Melanoma in situ of other part of trunk

D49.0

Neoplasm of unspecified behavior of digestive system

D49.1

Neoplasm of unspecified behavior of respiratory system

D49.2

Neoplasm of unspecified behavior of bone, soft tissue, and skin

D49.3

Neoplasm of unspecified behavior of breast

D49.4

Neoplasm of unspecified behavior of bladder

D49.511 Neoplasm of unspecified behavior of right kidney

D49.512 Neoplasm of unspecified behavior of left kidney

D49.59

Neoplasm of unspecified behavior of other genitourinary organ

D49.6

Neoplasm of unspecified behavior of brain

D49.7

Neoplasm of unspecified behavior of endocrine glands and other parts of nervous system

D49.89

Neoplasm of unspecified behavior of other specified sites

D49.9

Neoplasm of unspecified behavior of unspecified site

J91.0

Malignant pleural effusion

ICD-10 CODES THAT ARE COVERED FOR RESPONSEDX TISSUE OF ORIGIN FOR Elite (Medicare

Advantage) Plans ONLY

C18.1

Malignant neoplasm of appendix

C18.9

Malignant neoplasm of colon, unspecified

C22.0

Liver cell carcinoma

C22.2

Hepatoblastoma

C22.3

Angiosarcoma of liver

C22.4

Other sarcomas of liver

C22.7

Other specified carcinomas of liver

C22.8

Malignant neoplasm of liver, primary, unspecified as to type

C22.9

Malignant neoplasm of liver, not specified as primary or secondary

C25.2

Malignant neoplasm of tail of pancreas

C25.7

Malignant neoplasm of other parts of pancreas

C25.8

Malignant neoplasm of overlapping sites of pancreas

C25.9

Malignant neoplasm of pancreas, unspecified

C33

Malignant neoplasm of trachea

C34.00

Malignant neoplasm of unspecified main bronchus

C34.01

Malignant neoplasm of right main bronchus

C34.02

Malignant neoplasm of left main bronchus

C34.10

Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.11

Malignant neoplasm of upper lobe, right bronchus or lung

C34.12

Malignant neoplasm of upper lobe, left bronchus or lung

C34.30

Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.31

Malignant neoplasm of lower lobe, right bronchus or lung

C34.32

Malignant neoplasm of lower lobe, left bronchus or lung

C34.80

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.81

Malignant neoplasm of overlapping sites of right bronchus and lung

C34.82

Malignant neoplasm of overlapping sites of left bronchus and lung

C43.51

Malignant melanoma of anal skin

C43.52

Malignant melanoma of skin of breast

C43.59

Malignant melanoma of other part of trunk

PG0364-03/11/2024

Page 5 of 8

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download