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UroSEEK: A Novel Non-Invasive, Urine-Based Test for Urothelial Cancers

A new test for urothelial cancers could detect mutations in DNA that have been identified for those cancers earlier than traditional tests. The earlier detection of urothelial cancer could lead to earlier treatment, and potentially better outcomes for patients.

George Netto, MD, Pathology Department Chair at UAB, discusses the UroSEEK non-invasive test that he helped to develop, that uses urine samples to seek out mutations in 11 genes that indicate the presence of DNA associated with bladder cancer or upper tract urothelial cancer (UTUC).
UroSEEK: A Novel Non-Invasive, Urine-Based Test for Urothelial Cancers
Featured Speaker:
George Netto, MD
George Netto, MD specialties include Anatomic Pathology, Cancer Genetics, Surgical Pathology, Urology.

Learn more about George Netto, MD

Release Date: July 30, 2018

Expiration Date: July 30, 2021

Disclosure Information:

Dr. Netto has the following financial relationships with commercial interests:

Consulting Fee - Roach, Brown, McCarthy & Gruber, P.C.

Dr. Netto does not intend to discuss the off-label use of a product. No other speakers, planners or content reviewers have any relevant financial relationships to disclose.

There is no commercial support for this activity.

Release Date:       July 30, 2018

Expiration Date:   July 30, 2021


Disclosure Information:

Dr. Netto has the following financial relationships with commercial interests:


o    Consulting Fee - Roach, Brown, McCarthy & Gruber, P.C.


Dr. Netto does not intend to discuss the off-label use of a product. No other speakers, planners or content reviewers have any relevant financial relationships to disclose.


There is no commercial support for this activity.



Melanie Cole (Host): A new test for urothelial cancers could detect mutations in DNA that have been identified for those cancers earlier than traditional tests. My guest is Dr. George Netto. He's the Chairman of the Pathology Department at UAB Medicine. Welcome to the show, Dr. Netto. As far as tumors of the upper and lower urinary tracts, speak a little bit about the etiology of bladder and urothelial cancers, and how common and widespread is this cancer?

Dr. George Netto, MD (Guest): Thank you for having me. Bladder cancer and the majority of bladder cancer are urothelial carcinoma, so I'll use this terminology interchangeably, and are very common in the United States alone. Last year there were over 18,000 cases that led to 18,000 deaths. So it's a major healthcare issue, and it involves a lot of procedures and long-term follow-up to patients, and it leads to millions of dollars of cost to the healthcare system, in addition to the morbidity and mortality associated with it.

The etiology of urothelial carcinomas in general, and these are the tumors that affect upper and lower tracts starting with the renal pelvis and ending with the urethra, is strongly related to smoking and to environmental factors. Exposure to chemicals, certain infectious diseases as in the Nile Valley and South America, but mainly smoking and less so predisposition from inherited or familial diseases.

Melanie: Dr. Netto, how important is the early diagnosis as being crucial to improve outcome prediction? And can the earlier detection of urothelial cancers lead to earlier treatment and potentially better outcomes for patients?

Dr. Netto: The answer is it's very important. Most of bladder cancers do present as what we call superficial disease, early stage disease, and the problem with those is reoccurrence. So detecting the reoccurrence very early on in that group of patients is important because clearly it will prevent these patients from going underdiagnosed with the progression and progressing to a more lethal disease. But then you do have a subset, at least a quarter of bladder cancers that at time of presentation it's already a higher stage disease, what we call muscle invasive disease, and those, the prognosis is continued until recently to be very bad where overall five year survival it's around 50% despite radical surgery and adjuvant therapy.

There are some changes that occurred in the last few years that have improved upon this outcome in a subset of patients, but clearly the more we detect people in early disease, the less can have presenting with muscle invasive and the outcome in the early disease is better. And then if we also monitor them with a test that is effective, we will be able to early on detect the reoccurrences and prevent those patients from even progressing to a higher stage disease.

Melanie: Tell us about UroSEEK. How was it developed and what is it?

Dr. Netto: So UroSEEK is a noninvasive urine-based method- molecular method for detecting bladder cancer and upper tract urothelial carcinoma in general. And when I say urine-based, so it's focused on detecting driver mutation and the DNA- the tumor DNA that is shed, because cells shed in the urine, and usually the traditional way of detecting the cells is cytopathology, meaning you put the cells on a slide and you look under the microscope, which is the sensitivity of that method for certain tumors is low and it's dependent on a pathologist actually examining those cells.

UroSEEK on the other hand detects the DNA of these cells and within the DNA identify mutations and abnormality and deploy the DNA that will point us to the presence of tumor cells in the urine.

Melanie: Tell us the advantage of UroSEEK over cytology or combined with cytology.

Dr. Netto: So as I mentioned, cytology clearly is for the most part the gold standard looking at urine specimens, but more and more as liquid biopsies with other liquid like plasma and blood, urine is becoming a good source for DNA- tumor DNA be it within cells, what we call cellular DNA, or even cell free DNA. Our test is cellular-based DNA, and the advantage is that the sensitivity of the test is much higher than cytology, specifically in those tumors that are lower grade and those tumors that are pointed to that they have the tendency to reoccur and progress.

So while the specificity of cytology is high, meaning if you see a tumor cell then you're comfortable as a pathologist under a microscope that you have a tumor cell, then your diagnosis is definitive. The problem is a lot of times you cannot reach that degree of certainty based on looking at the cells under the microscope and you end up with many diagnoses of equivocal diagnoses that really do not help the urologist and the patient. And then the next step will be having to have an invasive procedure, which is cystoscopy in this case, where you go in and you look if the suspicion is in the bladder or upper tract, you go all the way up and looking for the tumor visually and doing biopsies. Clearly that procedure that is not favorable, and so the less we do of this, the less cost and less inconvenience to a patient and it has a lot of potential complications.

Combination of the best scenarios we've found so far, and this is where we hope our test will impact practice, is in combination with cytology. So let's get what works and add to it and improve upon it. So cytology, when it works, when it detects, that's fine. It's those cases that are equivocal and where cytology is unable to give us a diagnosis, going deeper now and looking at the DNA with a test that is very sensitive and maintain the specificity could be advantageous.

Melanie: What are the clinical indications for institutions? Speak about the patient selection criteria for this test, and also do you envision this becoming a standard screening test?

Dr. Netto: So the clinical indication, there are two settings where we see this test going into effective standard of care. The first setting is what we termed screening or early detection. Clearly not everybody who's walking the street we need to screen for bladder cancer, but anybody who has reason to go see the physician or a urologist, either a general practitioner or a urologist, because they found blood in their urine, for example, or have some symptoms of lower urinary tract that lead to a suspicion of cancer. Before doing cystoscopy, so these are patients who do not have a prior diagnosis of malignancy, of bladder cancer or upper tract either, then there is that suspicion, you can start with cytology and the current standard is you start with cytology if you have a persistent hematuria either under the microscope when you do your urine lab test, or for whatever reason that test can be ordered because of symptoms, for example especially in a smoker which we know is high risk.

So these patients who are somewhat riskier because of their more clinical presentation, be it hematuria or lower urinary tract symptoms, will be great candidates for this test in combination of cytology. So that's the early detection or screening part.

The other part is the monitoring and the surveillance setting. So these are- the 80,000 patients that I talked- that I mentioned last year, those are all going to need to be followed up. And some of them are followed up for years, every three months with a repeat cytology, every six months with a cystoscopy, just to prevent progression. That is another important cohort where the test in combination with cytology, so in the surveillance setting, can tell us early on that the tumor is coming back and has the potential to progress to a higher stage, where this test could be very instrumental. More importantly, if we get to the point where this test can- the negativity of this test can do away with cystoscopy and postpone the follow-up cystoscopy, that could be of tremendous value.

Melanie: Looking forward to the next ten years in the field, Dr. Netto, what do you feel will be the most important area of the research? Give us a little blueprint for future research.

Dr. Netto: So I first started by saying where do I see it in terms of early detection, because UroSEEK is the main topic of today's podcast, but I think we still have some work to do. The plan is to take this FDA approval, and this is not the only molecular method of detection, there are others. So to compare it to others and see what combination or how can we improve early detection and surveillance in general. So that's at least in the foreseeable future that's going to become very important; refining the test, increasing the sensitivity, and specificity, bringing down the cost. Because this test is based on sequencing, and sequencing costs and technology is moving fast, so hopefully we'll bring down the cost and refine the performance characteristic of the test in addition to other tests that also other groups are working on.

As far as bladder cancer in general, there is tremendous excitement in bladder cancer finally after decades of stagnation and being- frustration from scientists and clinicians not being able to help our patients improve their outcome. Trials on immunotherapy have shown great promise in a subset of patients so there will be a lot of work on the horizon to identify who are those patients that are more likely to respond to immunotherapy because currently there are 25% to 30% of all newcomers, so we would like to identify those patients, we would like to find biomarkers for response to immunotherapy. The same is true for new adjuvant therapy, which is in the last decade, patients receive chemo prior- those with higher stage disease, they receive chemo prior to surgery, and only a subset also respond to new adjuvant chemotherapy. So finding biomarkers that can identify that subset, and hence direct the chemotherapy and the immunotherapy, be either in the new adjuvant or adjuvant setting to the right population of patients. That will help us improve outcome in general and focus on the right- treat the right population.

Melanie: So in summary as a wrap-up, Dr. Netto, tell other physicians what you would like them to know about the UroSEEK test for bladder cancer, and when to refer to the specialists at UAB Medicine.

Dr. Netto: The UroSEEK is one of the promising liquid 'biopsy' based testing in the realm of bladder cancer and urothelial carcinoma have great potential to impact the standard of care. In the upcoming year, we're planning on taking it through the FDA and once it becomes orderable, I think that two settings that I referred to earlier will be very, very useful settings to order such tests. Mainly patients with micro hematuria and any symptoms that lead the general practitioner or the urologist to suspect the presence of bladder cancer, and also those who have prior diagnosis of bladder cancer or upper tract, and the urologist is monitoring them long-term. So adding this test to the algorithm of follow-up will be extremely helpful.

Melanie: Thank you so much. It's absolutely a fascinating topic and such an interesting test. Thank you again for being with us today. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1(800) UAB-MIST. That's 1(800) 822-6478. You're listening to UAB MedCast. For more information on resources available at UAB Medicine, you can go to That's This is Melanie Cole, thanks so much for listening.