Partitioned analysis of survival of patients receiving gemcitabine/cisplatin chemotherapy with or without nivolumab immunotherapy for advanced bladder cancer

Urothelial cancer is a type of cancer that affects the urinary system, including the bladder, and it is especially dangerous when it becomes advanced or spreads to other parts of the body. Each year, thousands of people are diagnosed with this disease, many of whom face limited treatment options and challenging side effects.

In recent years, treatment has improved through the development of newer therapies such as immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs). ICIs help the body’s immune system recognize and fight cancer cells, while ADCs deliver targeted cancer-killing drugs directly to cancer cells. These treatments are sometimes combined with more traditional approaches like chemotherapy (a drug treatment that kills fast-growing cancer cells throughout the body) or surgery.

To understand whether a treatment works, researchers often look at outcomes like how long a person lives overall—called overall survival (OS)—or how long the cancer stays under control before it gets worse, known as progression-free survival (PFS). However, these measures may not fully reflect the benefits of immune-based treatments, especially for patients who are able to stop treatment but still keep the cancer under control.
We aim to study a new outcome called treatment-free survival (TFS). TFS measures how long patients can live without needing active cancer treatment, while still keeping their disease in check. This is important because time off treatment can mean fewer side effects, better quality of life, and lower treatment costs. Some patients may pause treatment because of side effects, while others may be stable enough that treatment is no longer needed. Understanding how long these periods last—and who benefits most—can help improve care decisions. We study TFS in the full context of patients' experience of overall survival, with and without active treatment, and without or without side effects of the treatment.

We will use a method called partitioned survival analysis, which tracks groups of patients through different stages of treatment and follow-up. This technique will help us calculate TFS and see how it relates to side effects and overall disease control. Our team has used this approach successfully in other cancers like melanoma (a serious form of skin cancer) and advanced kidney cancer, where we found that certain ICI-based treatments gave patients longer breaks from treatment with fewer side effects.

In this project, we will apply the same methods to people with metastatic urothelial cancer (urothelial cancer that has spread to other parts of the body), comparing those treated with standard chemotherapy (gemcitabine/cisplatin) to those treated with an ICI-based regimen (nivolumab in combination with gemcitabine/cisplatin). By doing this, we hope to better understand how these newer treatments can give patients meaningful time off therapy, improving their overall experience and guiding future treatment decisions.