Bladder cancer involves abnormal cell growth in the bladder lining. While traditional treatments included surgery, chemotherapy, and radiation, immunotherapy has emerged as a major approach. This therapy stimulates the body’s immune system to recognize and attack cancer cells. The success rate varies significantly depending on the cancer stage and the specific drug used. This article details the types of immunotherapy and their measures of success for both early-stage and advanced bladder cancer.
Immunotherapy Treatments for Bladder Cancer
Immunotherapy for bladder cancer uses two distinct methods: local and systemic. Localized treatment, known as intravesical therapy, is delivered directly into the bladder via a catheter. The most common agent is Bacillus Calmette-Guérin (BCG), a weakened form of the tuberculosis vaccine bacteria. BCG triggers a strong inflammatory reaction in the bladder lining, drawing immune cells to the site. This local immune activation targets and destroys cancer cells.
Systemic treatment involves immune checkpoint inhibitors, administered intravenously throughout the body. These drugs target the PD-1/PD-L1 pathway, blocking proteins cancer cells use to hide from the immune system. Blocking this pathway releases the immune response, allowing T-cells to recognize and attack cancer cells. Systemic therapy is primarily used for advanced disease that has spread beyond the bladder.
Defining and Measuring Treatment Success
The definition of “success” in bladder cancer treatment depends on the disease stage and the goal of therapy. For localized disease, the primary goal is preventing recurrence, measured using Disease-Free Survival (DFS). DFS tracks how long a patient remains free of cancer after treatment. Complete Response (CR) is also used, meaning all detectable signs of cancer have disappeared after therapy.
For advanced or metastatic disease, success focuses on reducing the tumor burden and extending life. Key metrics include Overall Survival (OS), which measures how long patients live after diagnosis. The Objective Response Rate (ORR) is also used. ORR combines the percentage of patients achieving a Complete Response (CR) and those achieving a Partial Response (PR), where the tumor shrinks significantly.
Efficacy for Non-Muscle Invasive Disease
Non-muscle invasive bladder cancer (NMIBC) is typically treated with intravesical BCG following tumor removal. BCG therapy is highly effective at preventing recurrence in about 60% to 70% of patients. However, up to 40% of patients will not respond or will experience recurrence within two years, a situation known as BCG-unresponsive disease. For patients with high-risk NMIBC, the risk of the cancer progressing to a more invasive stage is between 10% and 45% over five years.
For patients whose cancer does not respond to BCG, the systemic checkpoint inhibitor pembrolizumab offers a bladder-sparing alternative to surgical removal. In clinical trials for high-risk, BCG-unresponsive patients with carcinoma in situ, pembrolizumab achieved a Complete Response rate of 41% at three months. Of those who achieved CR, 46% maintained remission for at least 12 months. Other agents, such as intravesical gene therapy, have shown a 3-month complete response rate of 44%.
Efficacy for Advanced and Metastatic Disease
For advanced or metastatic bladder cancer, systemic immune checkpoint inhibitors are the standard treatment. The overall Objective Response Rate (ORR) for PD-1/PD-L1 inhibitors in this setting is generally around 20% to 25%. For patients whose disease progressed after initial platinum-based chemotherapy, the ORR for pembrolizumab was reported at 21%. Checkpoint inhibitors also offer the benefit of durable responses.
When used as a second-line treatment, these systemic inhibitors have shown a pooled one-year Overall Survival rate of approximately 43%. In the first-line setting, for patients who cannot tolerate standard cisplatin chemotherapy, monotherapy achieves an ORR of about 25%. Patients with higher PD-L1 expression tend to have a better response to the therapy. Newer combination approaches, such as a checkpoint inhibitor with an antibody-drug conjugate, have shown higher response rates, reaching up to 73% in initial clinical trials.