Fox Chase Researchers Identify Possible Biomarkers in Bladder Cancer Patients Receiving Therapy Before Surgery

PHILADELPHIA (June 18, 2020)—In a recent study, researchers at Fox Chase Cancer Center found that muscle-invasive bladder cancer patients with specific gene mutations have better survival outcomes when treated with chemotherapy before surgery.

“We published the outcomes for patients with muscle-invasive bladder cancer treated with cisplatin-based chemotherapy before surgery who had mutations in a set of DNA damage repair genes such as ATM, RB1, FANCC, compared to those who did not,” said Benjamin Miron, MD, author of the study and a first-year fellow in the Hematology/Oncology Program at Fox Chase. Miron conducted the study with Elizabeth Plimack, MD, MS, chief of the Division of Genitourinary Medical Oncology at Fox Chase, and with other researchers from Fox Chase and other cancer centers.

“We found that patients who had at least one mutation in one of these genes survived longer after receiving cisplatin chemotherapy before surgery than patients who did not,” Miron said. Cisplatin is a chemotherapy drug used to treat various types of cancer, including bladder, testicular, breast, and cervical cancer. In bladder cancer it is used as a neoadjuvant therapy to shrink a tumor before it is removed via surgery.

Miron said the study builds on previous work in which researchers found that mutations in these genes were indicative of a positive response to neoadjuvant therapy. In that study, researchers presented data from two groups of patients, one used as a discovery set and the other for validation purposes. The study showed that survival was significantly better in the discovery set and that a trend toward improvement in survival also existed in the validation group.

“We did not have the necessary follow-up to show statistical significance in our original report. Now with a median follow-up time of over six years, we show that these mutations are in fact predictive of longer survival times and that the finding is statistically significant,” said Miron.

According to the most recent study, the five-year survival rate for patients with at least one mutation was 85 percent, compared to 45 percent for patients without a mutation. Miron said biomarkers like the ones validated in this study are important tools used to guide conversations with patients and to help physicians recommend the best treatment options for them.

“We currently still recommend neoadjuvant chemotherapy with cisplatin-based chemotherapy and surgery to remove the bladder to all eligible patients with muscle-invasive disease regardless of the specific mutations in their tumors. However, these results informed the development of an ongoing clinical trial that is testing the use of these mutations as biomarkers to help guide treatment,” Miron said.

He added that since patients with these mutations have had excellent responses to chemotherapy, the goal of this ongoing clinical trial is to find out if these specific patients can be treated with chemotherapy alone and followed by close surveillance, sparing the need for surgery to remove their bladder.

The study, “Defects in DNA Repair Genes Confer Improved Long-Term Survival After Cisplatin-Based Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer,” was published in the journal European Urology Oncology.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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