BLADDER EPICHECK by Nucleix

After ~ a week of communication with Nucleix concessionaires in Scandinavia (it is not performed in Israel) and in Israel,  their Int'l product manager updated me today that sending a sample of mine to one of the labs in Europe, won't work.
They are trying to make Epicheck available in Israel in the near future.   (my Prof. says he's been hearing this for a year already )

Good health to all.

After I read the excellent!! information Joea73 shared, I asked the Prof. who is treating me whether he would like to compare what we received from Cytology with Epicheck.   His reply was that Epicheck is not available in Israel in the last 2 years.
I emailed Prof. Leibovitvh and Nucleisx. (hoping for a workaround) Not replying.

Dear Joea73,

Thank you very much!   Only Good news and the very best to you and to all the participants here.

I  do not know enough to tell which one to choose, but I have noticed urologists use cytology first and if the answer is not clear such as Atypical or suspicious for high grade urothelial carcinoma the urologist uses biomarker based urine analysis to confirm the result of cytology.

Cytology

Cytology test is based upon a cytopathologist examining dead or live cells in urine which were fallen from the bladder wall. 

In 2013, the  international cytoplathologists group published the new guidelines to improve the accuracy for cytology report and came up with 7 classifications (The Paris System).  The professor of Yale School of Medicine gave a webinar and the risk of malignancy of each classification based upon Yale's experience.    Notice if the cytology report says High Grade urothelial carcinoma, 90% were found with cancer.  Also, if cytopathology report says Negative for UHUC, 90% chance that there are no UGHC.  So I feel confident that I can use to check if I have HG bladder cancer or not.

Unsatisfactory/nondiagnostic     <5-10% 
Negative for HGUC                         0-10%
Atypical urothelial cells                  8-35%
Suspicious for HGUC                     50-90%
Low-grade urothelial neoplasm  ~10%
High-grade urothelial carcinoma  >90%
Other malignancy                           >90%

Epicheck

Epicheck is  biomarkers based urine test.  Epicheck checks changes in DNA methylation in proprietary 15 different genes which have been implicated for causing bladder cancer.   Because it is proprietary, I do not know what 15 genes are, but those genes are either tumor promoter genes and tumor suppressor genes.    Tumor promoter genes produce proteins which promote cancer, for example the protein which signals the cell to divide.    Tumor suppressor genes produces  proteins which prevents from a cell to become cancer. For example there are tumor suppressor proteins which will repair if DNA has errors during DNA replication.   DNA methylation disables genes to produce proteins.    So, if there are DNA methylations for a tumor suppressor gene,  the tumor suppressor protein is not produced, so DNA errors will not be corrected during the cell division, which leads to producing cancer cells.  Or, if DNA methylations are missing for Tumor promoter genes, tumor promoter protein will be produced, e.g. the protein to signal dell division to be produced, thus causing the cell to divide constantly.  There have been several studies associating DNA methylations to specific genes associated with bladder cancer.  Epicheck utilized finding from those studies to have come up with 15 different genes.
  
Below table shows cytology and other urine analysis available in the market.  If you scroll the bottom of the table, Sensitivity and Selectivity will be shown.  Different urine analysis tool uses different methods.  

One good feature of Epicheck is that the accuracy does not depend upon the experience of the analyst compare to cytology of which the accuracy depends upon the experience of the pathologist.

You are amazingly kind, Joea73.

I came across this technology yesterday, Prof. Ilan Leibovitch's hospital department is approx. 20 km from where I leave  
Seeing the complexity of tests' results characteristics, I thought it will be a good idea to write here, and hoped You will see and reply! 

I went quickly through what you wrote and will read it again now

If I may ask,  what would you choose?  Cytology or Epicheck?  (not sure both will be possible)
Prof. Leibovitch is associated with the medical org. I'm a member at, so I guess it should not be a problem for me to get it

Mil thanks.

I always get confused of selectivity and specificity so I apology ahead of time that there may be mistakes.  Anyway, I will try to explain to your questions.

First, I have checked the company web site of Nucleix.  I think the technology was developed by a company in Israel.  EPICHECK uses DNA methylation bio markers.  

The company website says  Sensitivity 91% (excluding TaLG) ,  Specificity  85%, and  Negative Predictable Value 99%(excluding TaLG).

Sensitivity
It is the probability that the urine test by EPICHECK says positive and the pathology report after the TURBT says also positive.                     I If the pathology report says positive, it is True positive.    False negative is when EPICHECK says negative, but the pathology says positive.

Sensitivity =  True positive  / (True positive + false negative)   excluding the test for TaLG due to inaccuracy

Eg.      91% =  100 /  (100 + 9)      Of 109 patients tested HG or CIS  by EPICHEK,  9 patients were negative by the pathology

Specificity
It is the probability that the urine test by EPICHECK says negative and the pathology report after the TURBT says also negative
If the pathology report says negative, it is True negative.   False positive is when EPICHECK says positive, but the pathology says negative.

Specificity =  True negative / (True negative + false positive)

Eg.    85% =  100 /  (100 + 15)      Of 115 patients  tested LG,HG, or CIS negative by EPICHEK,  15 patients were positive  by pathology


Negative Predictable Value (NPV)  excluding the test for TaLG due to inaccuracy
It is the probability of an individual being truly negative when EPICHECK says negative.

NPV =  True negative / (True negative + false negative) 

Eg.   99%   =  100 / (100+1)     If a patient  tested negative with HG or CIS by EPICHEK, 99% chance the patient will be not HG or CIS if  the tumor was analyzed by a pathologist.


Performance comparison of Cytology and EPICHECK

Cytology accuracy in prediction according to they study done by McGill University , Montreal, Quebec in Canada in 2015


Sensitivity = 84% for HG and CIS     16% for LG
Specificity = 86% 

When Cytology was used with another urine bio marker NMP22 BladderChek (N), the sensitivity improved to 94%.


So, specificity for cytology alone and EPICHECK are about the same, i.e. 86% vs 85%.   For sensitivity, EPICHEK is better 91% vs 84% for cytology alone. But, the combination of cytology and the biomarker N will improve sensitivity to 94%.



The company website
nucleix.com/bladder-epicheck/

Statistic for sensitivity, selectivity, and negative predictable value
geekymedics.com/sensitivity-specificity-ppv-and-npv/

The study of performance of cytology and other urine biomarkers
pubmed.ncbi.nlm.nih.gov/25037483/