The Lank Center for Genitourinary Oncology's Bladder Cancer Program at Dana-Farber provides leading-edge research and care to patients with bladder cancer, with a multi-pronged strategy whose ultimate goal is to cure more bladder cancer patients.
Chemotherapy and Immunotherapy
Chemotherapy with platinum drugs has been used to improve outcomes of patients with metastatic bladder cancer. More recently, there has been significant progress in the treatment of advanced bladder cancer after the approvals of PD1 and PD-L1 inhibitor immunotherapy drugs since 2016. These immunotherapy drugs can control the cancer for prolonged periods in some patients.
Despite these advances, most patients do not respond to the PD1 and PD-L1 inhibitors, and there is a need to improve treatment options for advanced bladder cancer. Platinum-based chemotherapy given intravenously before bladder removal surgery (radical cystectomy) for cancer invading the muscle layer beneath the superficial cells has proven to improve survival. However, many patients with muscle-invasive bladder cancer still have recurrent disease after radical cystectomy.
For cancers not invading the muscle, a weakened tuberculosis bacterium (BCG) is administered into the bladder to reduce the risk of regrowth of cancer after removal of tumor during a bladder scope procedure (cystoscopy). However, if the non-invasive cancer returns after BCG administration, the more aggressive cancers are treated by radical cystectomy.
Ongoing Clinical Trials with Our Multidisciplinary Experts
Toni Choueiri, MD, Director, Lank Center for Genitourinary Oncology
Dana-Farber's team of clinical investigators provides multidisciplinary research and care to bladder cancer patients. The team includes medical oncologists, urologists, radiation oncologists, and basic scientists and is led by Toni Choueiri, MD. Sonpavde, whose primary focus is the development of new drugs to treat bladder cancer, has authored over 300 papers, is co-chair of the Genitourinary (GU) Oncology Committee of the Hoosier Cancer Research network (HCRN), and is a member of the Southwest Oncology Group (SWOG).
Dana-Farber Cancer Institute is playing a national and international leadership role in the development of new therapies for bladder cancer. Clinical trials are ongoing to improve survival by combining PD1 or PD-L1 inhibitors with platinum chemotherapy or other immunotherapy drugs. Clinical trials are also studying immunotherapy drugs as pre-operative (neoadjuvant) or post-operative (adjuvant) therapy to kill cancer cells more effectively and improve the cure rate.
Our Bladder Cancer Program offers access to a pipeline of promising new drugs and innovative clinical trials for every stage of the disease. In particular, BLASST (Bladder Cancer Signal Seeking Trials) -1 and -2 are innovative Dana-Farber-investigator-initiated trials that develop new immunotherapy drugs and combinations for neoadjuvant therapy.
Our collaborative team of clinical investigators has a major leadership role in most of these trials. Sonpavde is the national principal investigator (PI) or co-PI of multiple investigator-initiated, industry-sponsored, or NCI-sponsored trials. Bradley McGregor, MD, and Xiao Wei, MD, MAS, from Medical Oncology; Mark Preston, MD, MPH, and Matthew Mossanen, MD, from Urology; and Kent Mouw, MD, PhD, from Radiation Oncology, are all integral members of the Bladder Cancer Program and are leading multiple studies at the local or national levels.
Additionally, our clinical research protocols investigate tumor and blood collected from patients, coupled with their clinical outcomes (e.g., response to therapy, survival). These research efforts help to inform the molecular underpinnings of sensitivity — as well as resistance — to treatment; this is critically important for developing new treatments to improve patient outcomes.
Molecular Pathways Leading to Precision Cancer Medicine
The data collected by our Gelb Center's bladder cancer database enables Dana-Farber scientists focused on bladder cancer (David Kwiatkowski, MD, PhD, Eliezer Van Allen, MD, Kent Mouw, MD, PhD) to identify molecular pathways associated with response to chemotherapy and immunotherapy, in order to develop precision medicine. These studies involve multidisciplinary collaboration, including with the pathology team (Michelle Hirsch, MD, PhD, Justine Barletta, MD, Sabina Signoretti, MD). This team of accomplished translational scientists has published papers in major journals such as Science, Cell, and Nature.
Ongoing translational studies in collaboration with the Broad Institute are also planned, to analyze metastatic cancer cells and individual single cells in order to understand the evolution of mechanisms of resistance.
Improving Diagnostics
In addition to therapeutic investigations, clinical investigators are collaborating with the Dana-Farber Radiology team to improve diagnostics for bladder cancer. Muscle-invasive bladder cancer has been notoriously difficult to accurately stage (determine the true extent of disease) with routine scans. Heather Jacene, MD, is leading a study to evaluate a novel nuclear medicine technology for staging. Atul Shinagare, MD, is studying the different patterns and imaging biomarkers of radiographic response to immunotherapy in patients with metastatic bladder cancer.
