Bladder Cancer: Catching Up at Last
Bladder Cancer: Catching Up at Last
Editor's Note: Compared with other cancer types, there have been few clinical advances in the treatment of bladder cancer over the past 20 years, and the standard of care and clinical outcomes have remained relatively unchanged over this period. In the 70% of newly diagnosed patients who have non-muscle-invasive disease, recurrence is seen in up to 80% and stage progression in 15% to 20%. Patients with muscle-invasive bladder cancer are at high risk for progression; regardless of treatment, the 5-year overall survival rate is around 50%. A clear survival benefit has been demonstrated with cisplatin-based chemotherapy in the neoadjuvant setting in muscle-invasive bladder cancer, but this treatment remains underutilized. It is apparent that many patients do receive this therapy, which is associated with significant adverse events and has no predictive biomarkers to help select patients who would respond to it. But targeted therapies are in sight. Increased understanding of the tumor biology has led to the identification of multiple targets in bladder cancer, and ongoing clinical trials are providing exciting evidence of the potential benefit of targeted agents, both new and already approved in other cancers.
Matthew D. Galsky, MD, Associate Professor of Medicine, Hematology and Medical Oncology at Icahn School of Medicine at Mount Sinai, and Director of Genitourinary Medical Oncology at Tisch Cancer Institute, New York, New York, spoke with Linda Brookes, for Medscape, about the progress being made in the development of targeted therapy for bladder cancer and the challenges that remain for clinicians and patients faced with current treatment options.
Medscape: Why is it that chemotherapy known to be beneficial in bladder cancer continues to be underutilized?
Dr. Galsky: The benefit is perceived as modest by some and perhaps not worth the potential toxicity associated with the treatment. Also, there are distinctions between patients enrolled in clinical trials and the average population of patients with the disease. The median age of bladder cancer diagnosis is in the 70s, but if you look at most of the clinical trials that have been done in the perioperative setting, the median age of patients enrolled in these trials is in the 60s. There is a disconnect between the standard of care established in clinical trial data and what can actually be delivered to the community of patients with the disease.
Medscape: How could targeted therapies change this scenario?
Dr. Galsky: Targeted therapy can potentially be a great equalizer in this disconnect, because as treatments get better, as they work in a higher proportion of patients, as they become more convenient, and as they become safer, the threshold for their use in certain patient populations changes. If there is a drug that is given orally, that is well tolerated, that works in a high proportion of patients, certainly we would have a much easier time using that treatment even in older patients with some comorbidities than if we were giving multiagent, cisplatin-based chemotherapy. A better understanding of which patient populations might benefit from certain treatments is needed. And I think that bladder cancer is really poised to become a model cancer for precision medicine, rather like lung cancer has been, because of the abundance of molecular alterations that are potentially targetable with drugs that are already in the clinic or in clinical development.
Disconnect in the Standard of Care
Editor's Note: Compared with other cancer types, there have been few clinical advances in the treatment of bladder cancer over the past 20 years, and the standard of care and clinical outcomes have remained relatively unchanged over this period. In the 70% of newly diagnosed patients who have non-muscle-invasive disease, recurrence is seen in up to 80% and stage progression in 15% to 20%. Patients with muscle-invasive bladder cancer are at high risk for progression; regardless of treatment, the 5-year overall survival rate is around 50%. A clear survival benefit has been demonstrated with cisplatin-based chemotherapy in the neoadjuvant setting in muscle-invasive bladder cancer, but this treatment remains underutilized. It is apparent that many patients do receive this therapy, which is associated with significant adverse events and has no predictive biomarkers to help select patients who would respond to it. But targeted therapies are in sight. Increased understanding of the tumor biology has led to the identification of multiple targets in bladder cancer, and ongoing clinical trials are providing exciting evidence of the potential benefit of targeted agents, both new and already approved in other cancers.
Matthew D. Galsky, MD, Associate Professor of Medicine, Hematology and Medical Oncology at Icahn School of Medicine at Mount Sinai, and Director of Genitourinary Medical Oncology at Tisch Cancer Institute, New York, New York, spoke with Linda Brookes, for Medscape, about the progress being made in the development of targeted therapy for bladder cancer and the challenges that remain for clinicians and patients faced with current treatment options.
Medscape: Why is it that chemotherapy known to be beneficial in bladder cancer continues to be underutilized?
Dr. Galsky: The benefit is perceived as modest by some and perhaps not worth the potential toxicity associated with the treatment. Also, there are distinctions between patients enrolled in clinical trials and the average population of patients with the disease. The median age of bladder cancer diagnosis is in the 70s, but if you look at most of the clinical trials that have been done in the perioperative setting, the median age of patients enrolled in these trials is in the 60s. There is a disconnect between the standard of care established in clinical trial data and what can actually be delivered to the community of patients with the disease.
Medscape: How could targeted therapies change this scenario?
Dr. Galsky: Targeted therapy can potentially be a great equalizer in this disconnect, because as treatments get better, as they work in a higher proportion of patients, as they become more convenient, and as they become safer, the threshold for their use in certain patient populations changes. If there is a drug that is given orally, that is well tolerated, that works in a high proportion of patients, certainly we would have a much easier time using that treatment even in older patients with some comorbidities than if we were giving multiagent, cisplatin-based chemotherapy. A better understanding of which patient populations might benefit from certain treatments is needed. And I think that bladder cancer is really poised to become a model cancer for precision medicine, rather like lung cancer has been, because of the abundance of molecular alterations that are potentially targetable with drugs that are already in the clinic or in clinical development.
