Advertisement

What if nmibc does not respond to treatment?

An overview of second-line therapies for non-muscle invasive bladder cancer (NMIBC), including immunotherapy.

Updated on August 15, 2025

One way to think about cancer treatments is in terms of first-line therapies and second-line therapies. First-line therapies refer to the initial treatment that is used for a cancer. Second-line therapies are treatment options that are used when a cancer has not responded to a first-line therapy or the cancer has stopped responding.

Non-muscle invasive bladder cancer (NMIBC) refers to cancer that has formed in the inside of the bladder but has not grown into the deeper layers of the bladder. Most bladder cancers (75 percent) are categorized as NMIBC at the time of diagnosis.

First-line treatments for NMIBC

While every case of NMIBC is different, in most cases treatment will begin with a procedure called transurethral resection of bladder tumor (TURBT). This is a minimally invasive procedure to remove the tumor or tumors growing inside the bladder.

TURBT is also an essential part of diagnosis. Once the tumor is removed, it will be examined in a lab, which provides crucial information about the cancer and how it is behaving. This information is used to stage the cancer, assign a risk level (low, intermediate, or high), and guide the next steps in treatment.

NMIBC has a high rate of recurrence. TURBT may include or be followed by additional steps to kill off remaining cancer cells or reduce the risk of cancer cells coming back:

  • The surgeon may use electric current to burn the area where the tumor was removed.
  • The surgeon may also use a high-energy laser to destroy cancer cells that are not removeable by surgery.
  • TURBT is also often followed by intravesical therapy, where a liquid cancer medicine (either chemotherapy or immunotherapy) is delivered directly into the bladder.

Second-line therapies for NMIBC

Second-line therapies used in the treatment of non-muscle invasive bladder cancer include:

Additional intravesical therapy

Your healthcare team may recommend intravesical therapy using a different type of medication or a combination of medications. For example, if the cancer did not respond to immunotherapy, your providers may recommend chemotherapy. Cancers may respond differently to different types of cancer treatment.

Systemic therapies

Systemic therapies are cancer therapies that attack cancer cells throughout the body. Most are given with infusions (though some are given as oral medications). Systemic therapies for NMIBC include:

  • Immunotherapies, such as immune checkpoint inhibitors. These are drugs that disable mechanisms that cancer cells use to hide from the immune system, helping the immune system identify and destroy cancer cells.
  • Chemotherapy drugs, which contain substances that kill cancer cells and prevent cancer cells from multiplying. Numerous chemotherapy drugs are used to treat bladder cancer, and some are used in combination with one another.
  • Targeted therapies, which target specific proteins or pathways that cancer cells require to grow and survive. Some targeted therapies contain a chemotherapy drug and are able to deliver chemotherapy to cancer cells with greater precision.

Additional surgery

A follow-up, more extensive TURBT may be performed. Or more extensive surgery to remove tumors may be recommended. In some cases, this may include removal of the bladder (cystectomy) to prevent the progression of the cancer. Removal of the bladder will require reconstructive surgery to enable the body to store and expel urine.

Making treatment decisions

NMIBC is a different experience for everyone, and the choice of what second-line therapy to use will depend on multiple factors—specific characteristics of the cancer (such as the grade and location), your overall health, and your treatment preferences and priorities.

Your healthcare team will be your best source of information. Before starting any treatment, it’s important to discuss how the treatment works, the goal of the treatment, the potential side effects, and how the treatment compares to previous treatments used.

Article sources open article sources

NCI Dictionary of Cancer Terms. First-line therapy.
NCI Dictionary of Cancer Terms. Second-line therapy.
Stephen W. Leslie, Taylor L. Soon-Sutton, and Narothama R. Aeddula. Bladder Cancer. StatPearls. August 15, 2024.
Richard S. Matulewicz and Gary D. Steinberg. Non—muscle-invasive Bladder Cancer: Overview and Contemporary Treatment Landscape of Neoadjuvant Chemoablative Therapies. Reviews in Urology, 2020. Vol. 22, No. 2.
American Cancer Society. Tests for Bladder Cancer.
American Cancer Society. Bladder Cancer Surgery.
American Cancer Society. Intravesical Therapy for Bladder Cancer.
NCI Dictionary of Cancer Terms. Systemic therapy.
Gary D. Steinberg. Bladder Cancer Treatment Protocols. Medscape. May 15, 2024.
American Cancer Society. Chemotherapy for Bladder Cancer.
National Cancer Institute. Erdafitinib.
Florian Lordick, Maximilian Merz, et al. Antibody-Drug Conjugates as a Targeted Therapeutic Approach Across Entities in Oncology. Deutsches Arzteblatt International, 2023. Vol. 120, No. 19.
National Cancer Institute. Questions to Ask Your Doctor about Treatment.

Featured Content

article

Questions when starting a new treatment for NMIBC

What to ask when discussing medication or surgery for non-muscle invasive bladder cancer (NMIBC).
article

An overview of risk groups for NMIBC

An overview of low, intermediate, and high-risk non-muscle invasive bladder cancer (NMIBC).
article

How do you know if immunotherapy is working?

Learn about monitoring treatment response and side effects when treating cancer with immunotherapy.
article

3 lifestyle changes to make after a bladder cancer diagnosis

Habits to change and habits to adopt to give yourself the best chance of success when treating bladder cancer.