Rapid Autopsy Offers New Insights into Advanced Bladder Cancer Research and Treatment

There are many challenges facing the treatment of advanced bladder cancer due to the lack of information about the genomic differences between the varied advanced forms of the disease.

A recent study found that using rapid autopsy to compare genomic features of tumors in a group of patients with end-stage bladder cancers could lead to better treatment outcomes and make great strides for bladder cancer research.

Rapid Autopsy Program for Advanced Bladder Cancer

The study — led by Dr. Andrew Hsieh, a physician and scientist at Fred Hutch, and colleagues – focused on the genomic differences between metastatic lower tract urothelial carcinoma (LTUC) and upper tract urothelial carcinoma (UTUC). In turn, the research team aspire to create new treatments that can selectively target these changes and change the lives of patients living with cancer.

Bladder cancer, for many years, has had only one group of therapies that was effective (chemotherapy) which are considerably toxic, according to Hsieh. Over the past five years, there has been a dramatic shift in the way scientists and oncologists look at the advanced stage disease, thanks to immuno-oncology. However, immuno-oncology is not for everybody, Hsieh pointed out. He estimated that approximately 80% of patients with bladder cancer don’t derive much benefit at all from immunotherapy, which leaves many people falling through the cracks.

More recently, an FGFR regimen was approved by the Food and Drug Administration, which still gives patients with bladder cancer a total of only three therapies to control — but not cure – the disease, Hsieh noted. The rapid autopsy program will be a resource for many groups and this program, according to Hsieh, has the potential to push forward bladder cancer science.

“We really can’t (treat aggressive bladder cancer) like that or even take care of something like that unless we really know what’s happening under the hood,” said Hsieh. “But in order to do that, we need to get tissue specimens from patients who have this type of disease. It’s really, really difficult to acquire this when patients are still alive, mainly because that would require extensive biopsies which can come with side effects — bad side effects.”

Therefore, the rapid autopsy program is “banking on altruism of patients who really have a vision for seeing this disease crushed in the years to come. They want to use their tragedy to become another person — and the world’s – hope,” he added.

The researchers performed whole exome sequencing on matched primary (seven samples) and metastatic (30 samples) tumor samples from seven patients with metastatic urothelial carcinoma collected via rapid autopsy, including three patients with UTUC and four patients with LTUC.

The rapid autopsy program for patients with bladder cancer has existed for three years and is expanding. The program has conducted approximately 19 rapid autopsies on patients who died from bladder cancer. There about eight patients who have already consented to participate once they pass, according to Hsieh.

“Individuals who are inclined to donate their tissues will do so upon their death, and we have a 24-hour on-call team, ready to collect these tissues from multiple sites in the patient’s body,” said Hsieh. After the tissue samples are taken, the patient’s body is returned to the family.

Rapid Autopsy: A Widow’s Perspective

Dan Stinchcomb, who held a doctorate and was the chief scientific officer of the Infectious Disease Research Institute, died on Feb. 21, 2019, after receiving a diagnosis of bladder cancer. While Stinchcomb was neither aware of nor signed up as a donor for the rapid autopsy program prior to his death, Stinchcomb’s wife, Judy Boyle, shared with CURE® the unique story of her family’s choice to honor Stinchcomb and make a contribution to science and humanity.

First diagnosed as stage 2 cancer, Stinchcomb and Boyle met with Dr. Hsieh and colleagues at the Fred Hutch Cancer Center soon after the initial diagnosis and discovered their situation was much more precarious than they had been told. While looking at the very same slides and pathology reports, Hsieh and team discovered Stinchcomb’s cancer was stage 4 and that he had one of the rarest and most aggressive forms of bladder cancer.

Stinchcomb began radiation therapy and passed away eight days later. The radiation having weakened his intestinal track, as the cancer had grown through the area. He developed a leakage and Boyle rushed her husband to the hospital for emergency surgery, but doctors were only able to stabilize him. Eventually, he began to lose brain activity and would crash whenever he was taken off of the medications and treatments keeping his body alive. The family decided together that he would rather die naturally than live in a vegetative state.

When they informed Hsieh of their decision to let their loved one pass on his own, he presented the family with the opportunity of the rapid autopsy program. The doctor explained the benefits and use of the program and Stinchcomb’s family had to make a quick call while still processing Stinchcomb’s passing. Boyle, being a biologist, knew that this was what her scientist husband would have wanted.

“We didn’t know anything about it but when (Dr. Hsieh) explained it, it took us a nanosecond to say, ‘Well, this is what Dan would want,’” said Boyle. “It was a silver lining to an awful situation … if there was any way that we could prevent somebody else from going through this, knowing he had a rare and aggressive variance of bladder cancer.”

“It helped us feel like we could do something positive with that experience,” she added. “Somehow it made us feel better — it felt like there was something good coming out of losing Dan. It wouldn’t be a waste of a life so early. For all the good he’s done, this is something that he would have felt good about and I know he would have jumped at, given the opportunity.”

Boyle and her children found comfort and are glad they had the opportunity to turn the loss of their beloved husband and father into something that could benefit others who suffer from similar disease. Boyle is now a big proponent of the rapid autopsy program and encourages qualifying donors to consider this option to help advance bladder cancer research.

“It is such a common disease and there are so few cures and therapies available for disease,” Hsieh added. “It’s a really essential resource for the world. We can have these tissues and study these in-depth using the newest genetic, genomic and proteomic techniques to really understand what’s happening with the most aggressive forms of bladder cancer.”