Penn State Health Milton S. Hershey Medical Center is one of eight academic medical centers nationwide taking part in a clinical trial of Cxbladder — a noninvasive test that could spare thousands of patients the pain and expense involved in evaluating a diagnosis of hematuria.
Treatment of skull base tumors, including those affecting the pituitary gland, traditionally entailed opening the skull or making large incisions in the face and removing parts of the facial bones. These invasive procedures caused significant pain and scarring and required long hospital stays.
“We are the first site in the country to open the trial,” says Jay D. Raman, MD, FACS, Chief of the Division of Urology at Penn State Health Surgical Specialties. “As a medical organization, we’re willing to ask if the current standard of care is really the best way to do things.”
Laying the Groundwork
The trial, just one facet of the expansive program of clinical research at Milton S. Hershey Medical Center, began in October. Dr. Raman, his colleagues and the other teams around the country will research the accuracy of Cxbladder in comparison with the existing standard of care and observation for patients with hematuria, or blood in the urine.
Hershey Medical Center is the only academic medical institution in the region participating in the Cxbladder trial, which is recruiting a total of 800 patients from across all the participating medical centers.
That large, diverse sample of patients is key to producing robust findings, Dr. Raman explains. A nationwide pool of participants makes it easier to remove local and environmental biases, giving researchers a clearer picture of how well Cxbladder screens for possible urothelial carcinoma across a heterogeneous patient population.
“Every area of the country has its own environmental and toxin risk factors,” Dr. Raman adds. “For example, some of the risk factors we have in central Pennsylvania, including exposure to farming chemicals and tobacco, may be very different than a medical center in Los Angeles. The broad pool will help us cancel out those factors and get an accurate look at the test’s effectiveness.”
Advancing the Gold Standard
Patients with microscopic hematuria have a 5%–7% likelihood of having urothelial carcinoma. That rises to as high as 10%–15% when the hematuria is visible. About 80,000 Americans will be diagnosed with urothelial carcinoma in the next year, and approximately 17,000 Americans will die from it. It is the fourth most common cancer in men, according to the American Cancer Society, and along with sex, risk factors include age and tobacco use.
The gold standard for confirming a diagnosis of urothelial carcinoma — cystoscopy — is invasive and uncomfortable for patients, and it must be performed by a urologist. Because the test is painful and patients are sometimes hesitant to follow through with the screening, urologists must weigh the risk of a patient having urothelial carcinoma against the effects of the test involved to confirm the diagnosis.
This is where Cxbladder could revolutionize diagnostic protocols. It is a simple urine test that can be conducted in a wide range of medical office settings, and it is noninvasive — no different from virtually any other urine screening.
“Cxbladder assesses the RNA in voided urine,” Dr. Raman explains. “The test uses the expression of five different genes to give the patient a risk score, allowing us to better estimate the likelihood of the patient actually having urinary tract cancer. These biomarker studies can be superior to urine cytology for diagnosing smaller, less aggressive tumors. Tests like Cxbladder can help patients in two key ways — one by allowing for earlier diagnosis of cancer, the other by excluding patients whom we don’t need to evaluate with more invasive tests.”
The Testing Protocols
All patients in the clinical trial will undergo the initial component of the Cxbladder test, Triage, the findings of which will determine which patients move on to the next part of the test, Detect. Patients will also take part in the screening protocol recommended for their risk level under existing clinical standards. This means low-risk patients will use an observational approach in addition to taking the Cxbladder test.
Patients who screen for a higher likelihood of urothelial carcinoma during the Detect phase of the Cxbladder test will move forward with cystoscopy and imaging to confirm a diagnosis or rule out the disease as the cause of their hematuria.
Unlike screenings that require multiple exams and appointments, Triage and Detect can be performed using the same sample.
“We can even perform Triage and Detect simultaneously,” Dr. Raman explains. “The Triage test is a large-population test designed to rule people out immediately. The Detect test looks at the threshold and determines how strong the need for further evaluation is. It takes more personal risk factors into account.”
Positive results on both tests can underscore patients’ need for cystoscopy, providing them the clarity they need to overcome concerns that they could be undergoing an invasive procedure when it might not be necessary.
“The patients will know they need the screening when they’ve had these tests,” Dr. Raman says. “This could help them realize the importance of cystoscopy to rule out cancer in their case.”
“At Penn State Health Milton S. Hershey Medical Center, we’re constantly looking for new research opportunities in urology and other areas. We want to ask the right questions. We are dedicated to finding ways we can improve patient care and integrate new and exciting technologies into our current best practices when appropriate. Even when trials show a new technology isn’t as effective, they still highlight ways we can move on to our next approach. Ultimately, it will be our patients who benefit from what we do.”
— Jay D. Raman, MD, FACS, chief of the Division of Urology at Penn State Health Surgical Specialties
Measuring Patient Comfort
The trial will also gauge patients’ pain levels and anxiety during both cystoscopy and the Cxbladder test. A test that takes patient comfort into account and can be performed noninvasively in an office setting will encourage screening among patients who present with hematuria, according to Dr. Raman. Ultimately, that might lead to earlier diagnoses of urothelial carcinoma, which has tremendous implications for reducing mortality rates.
“We’re missing patients with hematuria,” Dr. Raman says. “This test could potentially be performed by primary care physicians and internal medicine specialists. It’s a step that can help ensure everyone who presents with this condition is properly evaluated.”
That could bring treatment of patients with urothelial carcinoma more in line with treatment of patients who have related cancers, he adds.
“With urothelial carcinoma, early detection is vital,” Dr. Raman says. “We have solid rates of survival with prostate and kidney cancers. People with those cancers can be identified earlier and treated. It’s harder to identify urothelial carcinoma in the early stages under current protocols, and it has a significantly higher mortality rate. As urologists, we are not always screening everyone who presents with hematuria because the workup can be more intensive for the patient than the diagnosis. But effective, early evaluation can make a positive difference.”
Dr. Raman and his team are actively recruiting participants who are at either high or low risk for urothelial carcinoma.
“Anyone who presents with hematuria is eligible for this trial,” Dr. Raman says. “We’ll work with the patients, ask them questions, decide which risk category they fall under and evaluate them accordingly. We encourage physicians who have patients presenting with hematuria to contact us.”
To learn more about the Cxbladder clinical trial, call 717-531-5930.