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.