Urine Test Used to Individualize Bladder Cancer Treatment

Bladder cancer is the most common urologic cancer in China and is in the top 10 most common cause of cancer death in the USA, leading to approximately 17,000 deaths in 2018.

Currently no method is available to predict which patients will respond to therapy and, apart from new and limited use of immunotherapy, treatment regimens for bladder cancer have not improved and survival rates have not increased in the last 30 years.

A large team of investigators from Georgetown University Medical Center (Washington, DC, USA) and Fudan University (Shanghai, China) have devised a very promising non-invasive and individualized technique for detecting and treating bladder cancer. The scientists adapted a conditional reprogramming (CR) technique to explore the possibility of establishing bladder cancer cells from patients’ tumor tissues and urine samples and applied the cultures for whole exome sequencing (WES) and drug testing.

The team compared tumor biopsies from 70 patients with individual urine specimens and both processed through CR cultures (CRC). Primary cells isolated from urine and tumor samples both rapidly formed CRC and representative three-dimensional compact spheroids. The investigators reported that the overall success rate of culturing urine CRCs was 83.3% (50/60), specifically, high-grade bladder cancer was 85.4% (41/48) and low-grade bladder cancer was 75% (9/12). The analysis of the mutation ratio for both patient tissue and corresponding CRC confirmed that both single nucleotide variants and DNA insertions and deletions were retained during the culturing.

After determining that the urine colonies and tumor tissue samples had matching molecular characteristics and genetic alterations, the scientists tested urine-based CRC cancer cells with 64 clinical oncology drugs. They found that overall the urine-based cancer cells were resistant to more than half of the drugs and they discovered that many of the urine cancer cells were highly sensitive to one of the drugs, bortezomib, which is currently being tested for a different GU tumor, urothelial cancer.

Shuai Jiang, MD, a urologist and the lead author of the study, said, “We also identified some mutations not identified in the original tumor biopsies, suggesting that the urine cell cultures better reflect overall tumor diversity than a single biopsy. The CRC technique may also expand our understanding of how low frequency mutations help lead to bladder cancer development and progression. Overall, CRC cultures may identify new actionable drug targets and help explain why this cancer is so often resistant to treatment.” The study was published on July 25, 2019, in the journal Protein & Cell.

Related Links:
Georgetown University Medical Center
Fudan University