Ahead of the American Association for Cancer Research annual meeting, being held April 14–18 in Chicago, Illinois, we spoke with Elizabeth Plimack, MD. Dr. Plimack is chief of the division of genitourinary medical oncology and director of genitourinary clinical research at the Fox Chase Cancer Center in Philadelphia, where she specializes in the treatment of genitourinary cancers, including bladder cancer. At the meeting, she will be discussing recent advances in systemic therapy for bladder cancer, in a presentation entitled, “Systemic Therapy for Locally Advanced and Metastatic Bladder Cancer: A Rapidly Evolving Landscape.”
—Interviewed by Anna Azvolinsky
Cancer Network: First, can you talk about the standard surgical and therapy options for locally advanced disease that have been around now for a while, and then how these contrast with the options for metastatic bladder cancer patients?
Dr. Plimack: Sure. Bladder cancer has a variety of presentations. And in fact, the majority of people who develop bladder cancer have what is called noninvasive or localized bladder cancer, which can be treated with topical instillations and procedures done to the bladder itself.
Beyond that, there is a subset of patients with muscle-invasive bladder cancer, and that is what we talk about as locally advanced bladder cancer. Those patients can be cured of their cancer, but it requires what we call multimodality treatment with both chemotherapy and surgery and, in some cases, chemotherapy with radiation. The difference between that state and the metastatic state is that the locally advanced state we are treating with a curative intent and in the metastatic setting, although treatable, the cancer is not curable.
So the goals of care are different and the treatment paradigm is different. I can speak first about best practices for patients with locally advanced muscle-invasive bladder cancer. The treatment algorithm for those patients is fairly well defined, with multiple guideline groups—NCCN [National Comprehensive Cancer Network], the AUA [American Urological Association], and the European groups recommending chemotherapy prior to surgery to increase the chance of a cure, defined as being disease-free at 5 years. We know that adding chemotherapy prior to treatment (typically surgery), helps. Recently, novel developments suggested that chemotherapy alone may be curative for a subset of patients, perhaps 10% to 30% of patients, and we are finding trials in that space to allow for patients to keep their bladders when chemotherapy is curative. I will be speaking about that in my talk at AACR.
Cancer Network: What are some of the new treatment modalities that have recently been approved for either locally advanced or metastatic bladder cancer?
Dr. Plimack: In locally advanced disease, we have developed [potential therapeutic regimens] and have started to enroll in clinical trials, looking to identify complete responders to chemotherapy and allowing for bladder-sparing. Those are the trials that are ongoing but have not yielded data yet. We are waiting for data on the COXEN trial, a trial that randomized patients to gemcitabine and cisplatin chemotherapy or dose-dense chemotherapy, and that study will provide really important data on more modern chemotherapy regimens in this curative situation, and [on] response rates and cure rates.
But also, this trial will help us define a number of biomarkers, including the ‘COXEN’ biomarker for which the trial was designed. And again, we are waiting for data on all of those trials. In the metastatic setting, it’s a different story. We have had an explosion of data over the last 3 years, which has defined and changed how we treat metastatic patients. And I will be speaking about that in my talk at AACR as well.