Feature

Urine test shows potential for detection, personalized treatment of bladder cancer

Xuefeng Liu, MD
Xuefeng Liu

Investigators from Georgetown University Medical Center and Fudan University in China have developed a novel noninvasive and individualized technique for the detection and treatment of bladder cancer.

The technique uses a urine specimen and a method that cultures cancer cells called “conditional reprogramming” — which allows patients’ cells to grow indefinitely without genetic manipulation — to reveal the unique molecular underpinnings of each patient’s disease.

“This is the first study to show, using patient samples, that a ‘living liquid biopsy’ from urine can help determine treatment,” Xuefeng Liu, MD, professor of pathology and oncology and co-director of the Center for Cell Reprogramming at Georgetown University and member of Georgetown Lombardi Comprehensive Cancer Center, said in a press release. “This work also suggests that we might be able to grow and test cancer cells for treatment from other ‘living biomarkers’ found in blood and saliva. We are just at the beginning of this new diagnostic innovation.”

HemOnc Today spoke with Liu about what makes this technique unique, the results of the study and plans for additional research.

Question: How does this technique differ from others available for these patients?

Answer : Many techniques are available for research purposes and clinical practice. For urine-based technology, urine cytology is commonly used but, unfortunately, the sensitivity is quite narrow. Most patients with bladder cancer have to see a doctor routinely for long-term intrusive, uncomfortable, expensive cystoscopy every 2 to 3 months after surgery. This makes bladder cancer the costliest cancer of all cancer types. A urine cancer cells test is comfortable, fast and less expensive than what is currently used.

Q: How did you conduct the study?

A: In this rapid report, we took 50 mL of morning urine samples from 70 patients and processed the specimens through cultures. Within a couple of days, we could see the cancer cells growing in the petri dish. Primary cells isolated from urine and tumor samples rapidly formed cultures and represented 3D compact spheroids.

Q: Can you elaborate on your findings?

A: The overall success rate of culturing urine was approximately 84%. We will further increase the success rate to at least 95%. A truly important aspect of our findings that we have never seen before was that we were able to identify cancer cells in urine. This is a simple way to be able to predict cancer recurrence. Although bladder cancer is not one of the most common cancer types in the United States, it is very expensive type due to frequent recurrence. Therefore, we wanted to come up with an inexpensive way to predict recurrence.

Another advantage of this study was that we could predict response to a certain drug, which will make it easy to test how a drug treats a cancer cell in vitro. We found that many of the urine cancer cells were highly sensitive to bortezomib (Velcade, Takeda Oncology), which is currently being tested for urothelial cancer. Further, we can obtain urine samples at any time before and after treatment, which could allow us to obtain real-time pathologic conditions. For seven patients, we compared urine-based drug sensitivities with clinical responses to traditional treatment as well as to CT and PET follow-up images. Results of this analysis matched the patient’s clinical history and their urine-based conditional reprogramming culture findings, thus confirming and supporting the use of urine conditional reprogramming in clinical practice.

Q: What needs to be confirmed before this technique becomes available in practice?

A: We need to conduct the same experiment but with more patients to confirm these findings. If we can do this, I believe this will become a routine method for practice.

Q: What will future research entail ?

A: We need more collaboration with hospitals and clinicians to expand the patient population. We do not have perfect drugs for certain cancer types, but with this new test, we have a unique platform through which we can use the cancer cells from patients for drug discovery. With this test, we may be able to find a new treatment for our patients. – by Jennifer Southall

Reference:

Jiang S, et al. Protein Cell. 2019;doi:10.1007/s13238-019-0649-5.

For more information:

Xuefeng Liu, MD, can be reached at Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Road NW, Washington, DC 20057; email: xuefeng.liu@georgetown.edu.

Disclosure: Liu reports future royalties and payments from Propagenix as inventor of conditional reprogramming technology licensed to Propagenix for commercialization.

Xuefeng Liu, MD
Xuefeng Liu

Investigators from Georgetown University Medical Center and Fudan University in China have developed a novel noninvasive and individualized technique for the detection and treatment of bladder cancer.

The technique uses a urine specimen and a method that cultures cancer cells called “conditional reprogramming” — which allows patients’ cells to grow indefinitely without genetic manipulation — to reveal the unique molecular underpinnings of each patient’s disease.

“This is the first study to show, using patient samples, that a ‘living liquid biopsy’ from urine can help determine treatment,” Xuefeng Liu, MD, professor of pathology and oncology and co-director of the Center for Cell Reprogramming at Georgetown University and member of Georgetown Lombardi Comprehensive Cancer Center, said in a press release. “This work also suggests that we might be able to grow and test cancer cells for treatment from other ‘living biomarkers’ found in blood and saliva. We are just at the beginning of this new diagnostic innovation.”

HemOnc Today spoke with Liu about what makes this technique unique, the results of the study and plans for additional research.

Question: How does this technique differ from others available for these patients?

Answer : Many techniques are available for research purposes and clinical practice. For urine-based technology, urine cytology is commonly used but, unfortunately, the sensitivity is quite narrow. Most patients with bladder cancer have to see a doctor routinely for long-term intrusive, uncomfortable, expensive cystoscopy every 2 to 3 months after surgery. This makes bladder cancer the costliest cancer of all cancer types. A urine cancer cells test is comfortable, fast and less expensive than what is currently used.

Q: How did you conduct the study?

A: In this rapid report, we took 50 mL of morning urine samples from 70 patients and processed the specimens through cultures. Within a couple of days, we could see the cancer cells growing in the petri dish. Primary cells isolated from urine and tumor samples rapidly formed cultures and represented 3D compact spheroids.

Q: Can you elaborate on your findings?

A: The overall success rate of culturing urine was approximately 84%. We will further increase the success rate to at least 95%. A truly important aspect of our findings that we have never seen before was that we were able to identify cancer cells in urine. This is a simple way to be able to predict cancer recurrence. Although bladder cancer is not one of the most common cancer types in the United States, it is very expensive type due to frequent recurrence. Therefore, we wanted to come up with an inexpensive way to predict recurrence.

Another advantage of this study was that we could predict response to a certain drug, which will make it easy to test how a drug treats a cancer cell in vitro. We found that many of the urine cancer cells were highly sensitive to bortezomib (Velcade, Takeda Oncology), which is currently being tested for urothelial cancer. Further, we can obtain urine samples at any time before and after treatment, which could allow us to obtain real-time pathologic conditions. For seven patients, we compared urine-based drug sensitivities with clinical responses to traditional treatment as well as to CT and PET follow-up images. Results of this analysis matched the patient’s clinical history and their urine-based conditional reprogramming culture findings, thus confirming and supporting the use of urine conditional reprogramming in clinical practice.

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Q: What needs to be confirmed before this technique becomes available in practice?

A: We need to conduct the same experiment but with more patients to confirm these findings. If we can do this, I believe this will become a routine method for practice.

Q: What will future research entail ?

A: We need more collaboration with hospitals and clinicians to expand the patient population. We do not have perfect drugs for certain cancer types, but with this new test, we have a unique platform through which we can use the cancer cells from patients for drug discovery. With this test, we may be able to find a new treatment for our patients. – by Jennifer Southall

Reference:

Jiang S, et al. Protein Cell. 2019;doi:10.1007/s13238-019-0649-5.

For more information:

Xuefeng Liu, MD, can be reached at Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Road NW, Washington, DC 20057; email: xuefeng.liu@georgetown.edu.

Disclosure: Liu reports future royalties and payments from Propagenix as inventor of conditional reprogramming technology licensed to Propagenix for commercialization.