cxBladder is a urine test to predict if the patient has bladder cancer. cxBladder was developed by the company called Pacific Edge in New Zealand. I have noticed it has been more mentioned and used in the US since Medicare had approved cxBladder. Currently available urine analysis for bladder caners are described below.
Cytology relies on a pathologist to look at fragments of urothelial cells in the urine using a microscope by finding abnormal-looking cells or a block of cells and predicting with high accuracy if there are high-grade / CIS bladder cancers. Also, they can find low-grade bladder cancers but the accuracy is not high. Cytology has a much longer history of being used for diagnosing bladder cancer than cystoscopy. Incidentally, histology is the analysis of cancer samples that were obtained by a urologist during the TURBT procedure. The pathologist decides the grade and the stage of the sample and reports the result to the urologist.
FISH or uFISH has been around for more than 15 years. It is another urine analysis. It was developed and sold by Abbot - a US medical device company. The brand name of FISH is UroVysion. FISH stands for Fluorescence In Situ Hybridization. The urine which contains urothelial cells is mixed around and goes through proprietary chemical analysis to find abnormal chromosome 3, 7, 17 and if chromosome 9 position 21. The chemical processed urothelial cells highlight in the fluorescent red, green, aqua, and gold if abnormal chromosomes 3,7,17, and 9P21 are found respectively. Note that abnormalities in chromosomes 3,7,17 and 9p21are often found in bladder cancer cells. When FISH has developed almost 20 years ago, not many gene analyses were done for bladder cancer back then. So, I think they needed to depend on the analysis of chromosomes. So, we can say FISH is a bit old technology.
In 2004, the first complete human genome analysis was completed. In 2015, a paper was published, which analyzed genes that were found in invasive bladder cancer patients. Today, over 300 genes have been identified in bladder cancer.
cxBladder is a newer urine analysis that is based upon gene analysis.
It uses 5 different genes, which are known to show up in high numbers in bladder cancers.
cxBladder has two protocols. One is cxBbadder Triage and the other is cxBladder Monitor.
cxBladder Triage which is used to check if the urine contain cancer cells. cxBladder monitor is used to check if reccurence had happened in between cysoscopy, especially for high grade and CIS.
Both cxBladder Triage and Monitor chek if the urothelial cells found in the urine have high concentration of 5 bladder cancer causing genes - IGFBP5, HOXA13, MDK, CDK1, and CXCR2.
For Monitor, The formula to predict the exisitense of bladder cancer is G-Index = (0.79 × IGFBP5 – 1.60 × HOXA13 + 2.10 × MDK + 0.95 × CDK1 – 0.38 × CXCR2) .
The higher the total, the higher the possiblity that we find a cancer in the bladder. If the multiplier is possitive, the gene is tumor promotor gene. If the multipler is negative, the gene is tumor suppressor. In other word, the higher concentration of IGFBP5 is, the higher probability that there is a cancer in the bladder. The higher concentration of HOXA13 is, the less chance that there is a cancer in the bladder. Monitor protocol has high probability to be right to predict the existence of high grade /CIS cancer in the bladder.
But, that formula does not give sufficiently predictability, which can be used in clinical setting, the existense of low grade blader cancer. So, for Triage, to improve accuracy they added a phenotype or qualitative values comprising of age(>65), smoking history, male or female, frequency of gross hematuria
P Index = −3.78 + (0.81 × Age + 0.46 × Gender + 0.78 × Smoking history + 0.59 × Hfreq). The higher P-index is
the higher the probabiity of existence of cance in the bladder. So, if you are over 65, male, with smoking history and had multiple gross hematuria, P-INDEX = -3.78+0.81+.46+0.78+0.59 = -.1.14. If you are under 65, female, never smoked, no gross hematuria, P-Index = -.3.78. Then you add P-Index to G-Index. If the total score is 0, definetily no cancer in the bladder exist. If the score is 10, it is almost certain, the cancer is advanced and can be already metastatic. If it is less than 4, it is likely no cancer or low grade if it does exisit. If it is less than 4, there will be no need for cystoscopy. So, for hematuria for example, as Sara had mentioned, cxBladder can be used instead of cystoscopy which is more invasive and more expensive. Anyway, that is how Pacific Edge wants to increase the use of cxBladder in clinical setting.
I will post next the pictures of Histology (pathology), cystology urine analys, UroVysion (Fish), cxBladder for the reference . For some reasons, I cannot attach the pictures.
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