As an associate professor of urology in the University of Colorado Department of Surgery, Nicholas Cost, MD, was used to treating children with urologic cancers such as bladder cancer and kidney cancer. But when he began receiving referrals of children with other types of cancer who were having urinary tract issues, he became curious. Was there something about cancer treatment that was causing these young patients to develop lower urinary tract dysfunction?
“They were getting referred because they were having problems with voiding. It’s not a life-threatening condition, but it’s something that was really bothering kids and their families,” says Cost, a member of the CU Cancer Center. “We dug into it a little more, both clinically and in the lab, and we discovered a couple of drugs that are used commonly to treat childhood cancer and started to look at why they may cause urinary problems.”
Chemotherapy drugs as culprits
Cost and his fellow researchers identified two common chemotherapy drugs — vincristine and doxorubicin — that may affect bladder physiology and manifest clinically as lower urinary tract dysfunction. Vincristine can cause neuropathy, or nerve damage, and doxorubicin can cause myopathy, or muscle damage.
"Doxorubicin is infamous for causing cardiac muscle toxicity. Children who receive it can get early heart failure, because it’s toxic to the muscle,” Cost says. “And vincristine is known to cause damage to the nerves. Children can develop problems with walking, because it affects the long nerves down their legs. We thought maybe it was affecting the nerves to the bladder as well.”
Cost and his team began further study of those drugs in the lab, and they used a tool called the dysfunctional voiding scoring system (DVSS) survey to understand the types of dysfunction children were experiencing and how severe the symptoms were.
“It’s a 10-question survey that goes through a number of different things that could be happening, anything from having accidents to feeling a frequent need to urinate,” Cost says. “When they do go, are they able to empty their bladder completely?”
The results are in
Survey results showed that childhood cancer survivors who received vincristine and/or doxorubicin reported higher rates of lower urinary tract dysfunction than a control group of children who did not have cancer, and that female childhood cancer survivors reported more dysfunction than males.
“Historically, female patients already report a higher rate of lower urinary tract dysfunction, so there’s a slightly different bar for them on the scoring,” Cost says. “Therefore, when we do this work, we look at each gender specifically. What’s interesting is that in animal models, we see different effects in males and females, as well. We’re trying to present why we think it happens in both settings and think about sex as a biological variable.”
Further study underway
Cost first published his research on the issue in 2021 in the journal Pediatric Blood Cancer; since then he has conducted additional research, including studying a group of childhood cancer survivors who received other types of chemotherapy to better understand the contribution of a cancer diagnosis to lower urinary tract dysfunction. He is also conducting further research on patients with urinary tract dysfunction, using special calibrated toilets to study flow patterns and velocity. Additionally, his team is partnering with the veterinary oncology research group at Colorado State University to look at similar issues in dogs who were treated for cancer with these chemotherapies.
“What we’re trying to do in the lab is figure out exactly why it’s happening, on a molecular basis,” Cost says. “It’s premature to say we know enough yet, but there’s hope that if we identify the cause, there are things we can do to help prevent it.”
In the meantime, he hopes his research leads to early recognition of the condition and a screening effort to get those at risk into pelvic floor physical therapy, which has been shown to help children with voiding dysfunction.
“There may be a very targeted way to prevent side effects — while they get these drugs, they also get something that inhibits the side effect, too,” he says. “Most realistically, we will be able to more readily identify which patients are most at risk based on gender, age, and dose, and then if they have the side effects, get them into early corrective physical therapy. At the end of the day, our biggest goal is to give these childhood cancer survivors the best future lives they can have.”