Study establishes foundational landscape of tumor evolution in bladder cancer
· News-MedicalA new study published in Nature has established the foundational landscape of tumor evolution in bladder cancer and differences in the cancer subtypes, which could point toward better diagnosis and treatment of the disease.
Thousands of people will be diagnosed with bladder cancer every year. While nearly 80% of patients with bladder cancer survive, metastatic bladder cancer still presents significant problems. The natural history of metastatic bladder cancer is not fully understood, particularly rare subtypes, which becomes a challenge for clinicians to predict when it may appear and how best to treat it.
By reconstructing the evolutionary histories of 104 tumors from 20 patients, a research team from Fred Hutch Cancer Center and University of Washington determined that the earliest metastatic tumor was likely the primary source for widespread metastases.
"The major driver of death from bladder cancer is metastasis, and in order to understand and target it we needed better data to learn about how the tumors migrate and spread," said study co-senior author Gavin Ha, PhD, an associate professor in the Public Health Sciences Division at Fred Hutch and holder of the Shintaffer Family Endowed Chair in Bioinformatics. "We want to find earlier opportunities for intervention, so understanding the order of metastatic spread is important."
The team used a first-in-kind rapid autopsy program in collaboration with co-senior authors Ming Lam, PhD, a research associate professor in the Department of Urology at the University of Washington, and Omar Mian, MD, PhD, an associate professor in the divisions of Human Biology and Radiation Oncology at Fred Hutch. It allowed them to collect samples from advanced bladder cancer patients to better understand rare bladder cancer subtypes that have previously been understudied. It also allowed researchers to study multiple tumors from the same patients and dive deeper into the genomic architecture, the genes, DNA sequences and genetic variations that work together to shape physical traits, biological functions and disease.
Using the data collected in the rapid autopsy program, researchers identified that metastatic tumors seeded new metastases and fueled the spread of more aggressive bladder cancer subtypes from metastasis to metastasis.
Andrew Hsieh, MD, co-senior author, expert in prostate and bladder cancer and professor and associate director of the Human Biology Division, Fred HutchWhat we found is that perhaps metastases are the staging point for disease to spread to other places."
Researchers were also able to note distinct differences between all subtypes, including how each may distinctly develop metastasis and react to different treatments. In addition, researchers were able to show that subtype differences could be captured using circulating DNA from the blood, which provides a non-invasive approach for monitoring how the tumor evolves into more aggressive forms.
"We hope that these findings help us further examine whether a single metastases or residual metastasis could respond to more tailored therapies," added Hsieh, who holds the Larry and Virginia Gordon Endowed Chair in Prostate and Bladder Cancer Research at Fred Hutch.
Building on this work, a clinical study called the REINFORCE trial, led by Dr. Martin Ma, is investigating whether adding consolidative treatment, such as radiation therapy to the bladder or surgical removal of the bladder (radical cystectomy) coupled to ablation of all metastatic sites with SBRT, can safely arrest metastatic progression and delay cancer progression.
"We are grateful to all the patients and their families who have contributed to this study and entrusted us with an opportunity to help others," said Hsieh. "We are learning from their experiences with metastatic bladder cancer and are hopeful that their contributions will make the disease easier to bear for future patients."
Source:
Journal reference: