A Culture of Innovation: Breakthroughs in Bladder Cancer

May 16, 2017 | by Abe Rosenberg

Kristi Florin still remembers how it felt when she heard the news:
 
“Panic,” she said. “I was scared to death. I feared the worst.”
 
It was 2013. Florin, a Garden Grove, California, mother of three (and grandmother of five) was told she had Stage 3 bladder cancer. Having already lost her mother and a brother to cancer, the diagnosis was tough to accept.
 
“I thought to myself, 'This is it,'” she recalled.
 
But Florin's story has a happy ending, with an outcome that's becoming more common.
 
A ‘Stubborn’ Disease
 
Bladder cancer is a stubborn disease. Malignant cells in the bladder frequently grow back or pop up elsewhere, even if they're removed in their earliest stages.
 
But the City of Hope surgeons and scientists working to eradicate bladder cancer are equally stubborn. They are combining their skills and experiences to wage a multifront attack on this disease that strikes an estimated 79,030 Americans every year.
 
From improved surgical techniques which preserve quality of life, to an array of chemotherapy, immunotherapy and gene-based targeted therapy options, the outlook is improving.
 
After 12 weeks of chemo, Florin's bladder was removed in a 7.5-hour procedure (“My husband was a mess,” she said, smiling.) Much of it was done robotically (“Kind of trippy,” she admitted.) She was given a so-called “Indiana pouch” under her skin to collect urine. She uses a catheter every few hours to drain the pouch.
 
“In about eight weeks, I was feeling like myself again,” she recalled.
 
City of Hope’s Secret Weapon
 
At City of Hope, one of the most important advances employs neither scalpel nor syringe.
 
The secret weapon is people.
kevin-chan Kevin Chan, M.D.
“I can't say enough about our novel coordinated care pathway and how significant it is,” said City of Hope urologic surgeon Kevin G. Chan, M.D. “It really is a game changer.”
 
For patients facing bladder removal (or “cystectomy”) and reconstructive surgery, the coordinated care model deploys a team of professionals – a nurse, a case worker, a social worker and occupational and physical therapists – all of whom get involved on day one. “The patient meets all of them on the same day he meets me,” said Chan. The team helps the patient anticipate and avoid pitfalls and complications before, during and after surgery.
 
And it works.
 
Improving Outcomes
 
Depending on the procedure, bladder cancer surgery can have up to a 70 percent complication rate, a hospital stay as long as 10 days and a readmission rate as high as 30 percent. With coordinated care, all those numbers come down.
 
“Bladder surgery is a long journey,” said Chan. “Anything we can do to improve recovery is worthwhile.”
 
Improving recovery is also a major motivation behind the so-called “neobladder” procedure. Instead of an Indiana pouch or an external collection bag, Chan takes a section of the patient's intestine and fashions it into a substitute bladder, which in time functions much as the original.
 
Although the neobladder technique has been around for decades, the procedure is still quite rare – except at City of Hope, a leader in the field. While only about 5 percent of all cystectomy patients nationwide receive a neobladder, at City of Hope the ratio is closer to 50 percent. City of Hope surgeons continue to refine the procedure, doing more of it robotically and with smaller incisions, to minimize blood loss and speed recovery.
 
And with successful surgery, “recovery” can also mean “cure.”
 
“It's almost impossible to cure bladder cancer without removing the bladder, because cancerous cells return,” said Chan. “But with surgery, we can achieve a cure rate of 70 percent.”
 
Bladder Breakthroughs
 
Nevertheless, Chan and his colleagues look forward to the day when the need for surgery is minimized, even eliminated, thanks to advances in drug therapy. Here too, City of Hope is making significant progress, on several fronts:
 
A phase II clinical trial is underway to determine how well the targeted therapy drug VX970 works in combination with gemcitabine and cisplatin – two mainstay chemotherapy agents for bladder cancer.
Sumanta Pal - 800x800 Sumanta Pal, M.D.
“VX970 works at the DNA level, inhibiting a cancer cell's repair pathway,” said City of Hope medical oncologist Sumanta Pal, M.D, the lead investigator of this National Cancer Institute-supported trial. “It makes those cells more susceptible to damage, so the chemo can do a better job.”
 
Pal is also excited about the potential of another targeted therapy drug, BCJ398, which has been shown to stall the growth of cancer in patients with specific genetic mutations in their “fibroblast growth factor receptors” or FGFRs. “We're seeing a high response in those patients,” he said.
 
Another project seeks to better understand why cancer spreads beyond its original location. For some time now, scientists have believed that before malignant cells can migrate, benign cells have to undergo specific changes to pave the way. This is called the “premetastatic niche,” and Pal is running a 400-patient study to learn how it works in bladder cancer. Ultimately, that knowledge may yield new ways to stop cancer before it starts.
 
A Culture of Innovation
 
Those research forays are important, Pal said, because the drugs available today still don't work for most people. “We get about a 20 percent response rate to chemo or immunotherapy. We don't fully understand why, nor are we able yet to accurately identify who would fall into that 20 percent.”
 
Even so, efforts continue to try and increase those odds. Innovations like encasing chemo agents in nanoparticles may improve their delivery into the bladder while sparing healthy tissue. CAR-T cells are reinvigorating immune systems in patients with blood cancers and brain tumors, and it's hoped the same will be true for bladder cancer, “but that is still years away,” said Pal.
 
As for the here and now, Florin continues to marvel at how well she's doing. Four years after surgery she remains cancer-free, with no dramatic changes to her daily routine.
 
“My life is normal,” she said. “There's no sensation (from the Indiana pouch) at all. I'm healthy. I'm fine! And I'm so surprised, compared to where I was just a few years ago. It's like it's nothing!”
 
 

 

 

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