Cancer of Unknown Primary Test

[pathstudent]

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When we can't say exactly where the tumor came from via morphology, IHC and Radiology, our oncologists and rad-oncs have been asking us to send out for the so called CUP test.

I am very doubtful over these types of test and especially doubtful when dealing with unusual tumors which aren't at all like standard organ based tumors.

I know the test is FDA approved but has anyone seen any independent studies that validate it or question it?

 

[raspberry009]

I'm guessing this is a squame?

 

[BU Pathology]

1. Monzon FA, Lyons-Weiler M, Buturovic LJ, et al: Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol 27:2503-2508, 2009
2. Pavlidis N, Fizazi K: Cancer of unknown primary (CUP). Crit Rev Oncol Hematol 54:243-250, 2005
3. Varadhachary GR, Talantov D, Raber MN, et al: Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation. J Clin Oncol 26:4442-4448, 2008

 

[APCPPathologist]

Pathstudent - you are correct in that there is minimal info on the FDA approved test. There is the one retrospective study as mentioned by BU path. It's funny - if you read the FDA label - it is expressly not for "Cancer of Unknown Primary", but instead is a similarity score. As in similar to one of fifteen choices. If only the reality of surg path was so easy.

H. Intended Use: ​

<DIR>[FONT=Times New Roman,Times New Roman][FONT=Times New Roman,Times New Roman]

1. Intended use(s): ​

<DIR>

The Pathwork® Tissue of Origin Test is an in vitro diagnostic intended to measure the degree of similarity between the RNA expression patterns in a patient’s formalin-fixed, paraffin-embedded (FFPE) tumor and the RNA expression patterns in a database of fifteen tumor types (poorly differentiated, undifferentiated and metastatic cases) that were diagnosed according to then current clinical and pathological practice. This test should be evaluated by a qualified physician in the context of the patient’s clinical history and other diagnostic test results.​

</DIR></DIR>Limitations: The Pathwork® Tissue of Origin Test is not intended to establish the origin of tumors (e.g. cancer of unknown primary) that cannot be diagnosed according to current clinical and pathological practice. It is not intended to subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice, nor to predict disease course or survival or treatment efficacy, nor to distinguish primary from metastatic tumor. Tumor types not in the Pathwork® Tissue of Origin Test database may have RNA expression patterns that are similar to patterns in the database. Therefore, results cannot be used to distinguish tumor types in the database from tumor types not in the database.

What a joke - that FDA reviewer was obviously not attuned to our reality.
..

 

[KCShaw]

FDA approval != utility.

 

[GeoLeoX]

My experience with tests like this is that if you can't tell on morphology, IHC, etc (most often because it's poorly differentiated or expressing something weird for your differential) you often get an "indeterminate" result from the nucleic acid-based test. And you waste several thousand dollars.

 

[malchik]

Which raises the slightly more philosophical question of when should expression of a single or a few markers (IHC) or of several RNAs, as with the tests in question, trump histology? Histology (phenotype) is the result of all expressed and repressed genes, not just a few. Under the scope you're looking at the whole proteome, glycome, kinome, lipome(?), and any other -ome.

 

[GeoLeoX]

Which raises the slightly more philosophical question of when should expression of a single or a few markers (IHC) or of several RNAs, as with the tests in question, trump histology? Histology (phenotype) is the result of all expressed and repressed genes, not just a few. Under the scope you're looking at the whole proteome, glycome, kinome, lipome(?), and any other -ome.

Nothing bothers molecular pathologists more than the inability of clinicians to understand basic biology. Well said, sir.

The basis of prognosis and diagnosis is histology. But then again, why do we thinly slice a tumor, stain it, and then look at it under a microscope and think that represents the tumor?

We still have a ways to go before we achieve "total tumor characterization".

 

[deleted314957]

My experience with tests like this is that if you can't tell on morphology, IHC, etc (most often because it's poorly differentiated or expressing something weird for your differential) you often get an "indeterminate" result from the nucleic acid-based test. And you waste several thousand dollars.

lots of the gyrations we go thru with these carcinomas of unknown primary are a waste of time and money. According to Mark Wick's text regarding this subject( Metastatic carcinomas of unknown origin, Demos publishing 2008) there is only a 15% subset of patients with metastatic ca of unknown primaries who would fall into a "treatable" subset. These include tumors with neuroendocrine features, SCC involving cervical nodes, adenoca in women that present with axillary mets,peritoneal carcinomatosis in women, blastic bone mets in a man and midline malignancies in young men that are probably extragonadal GCT's.

 

[gbwillner]

lots of the gyrations we go thru with these carcinomas of unknown primary are a waste of time and money. According to Mark Wick's text regarding this subject( Metastatic carcinomas of unknown origin, Demos publishing 2008) there is only a 15% subset of patients with metastatic ca of unknown primaries who would fall into a "treatable" subset. These include tumors with neuroendocrine features, SCC involving cervical nodes, adenoca in women that present with axillary mets,peritoneal carcinomatosis in women, blastic bone mets in a man and midline malignancies in young men that are probably extragonadal GCT's.

I have been to several dinners sposored by these companies, and PCPs love them and order them frequently. Some, as you guys point out, just don't understand the biology and assume that if we could only identify the archetype of the unidentifiable tumor, they would have a Dx and expect the tumor to behave as such. Most of the talks I've seen only feed these ideas, as the labs that offer these tests will show how some TUO will match perfectly with the profile of some known entity, thus that is what the TUO is. Of course we know that just because the profiles are the same does not give you insight on how that tumor will behave. You need good prospective studies using these tests to show that TUO treated like its "archetype" have better outcome than those treated as " metastatic poorly-differentiated carcinoma". I'm willing to bet outcomes will be terrible regardless.

Anyway, other PCPs just want to have a Dx to give the family or need some treatment plan.

 

[pathstudent]

I have been to several dinners sposored by these companies, and PCPs love them and order them frequently. Some, as you guys point out, just don't understand the biology and assume that if we could only identify the archetype of the unidentifiable tumor, they would have a Dx and expect the tumor to behave as such. Most of the talks I've seen only feed these ideas, as the labs that offer these tests will show how some TUO will match perfectly with the profile of some known entity, thus that is what the TUO is. Of course we know that just because the profiles are the same does not give you insight on how that tumor will behave. You need good prospective studies using these tests to show that TUO treated like its "archetype" have better outcome than those treated as " metastatic poorly-differentiated carcinoma". I'm willing to bet outcomes will be terrible regardless.

Anyway, other PCPs just want to have a Dx to give the family or need some treatment plan.

Where are you that PCPs order this? That is absurd as PCPs don't treat cancer. In my experience it is exclusively oncologitsts, never a primary care physician.

 

[gbwillner]

Where are you that PCPs order this? That is absurd as PCPs don't treat cancer. In my experience it is exclusively oncologitsts, never a primary care physician.

I mistyped. I meant "clinician" since I don't know what specialty everyone is who attends these events.