Bladder Cancer Treatment Options

The bladder is an organ in the lower pelvis responsible for storing urine. When cells in the bladder start to grow out of control, they can form tumors leading to bladder cancer.

Urothelial cancer is the most common form of bladder cancer and impacts around 80,000 people per year. This form of bladder cancer starts in the urothelial cells that line the inside of the bladder. Urothelial cancer may also occur in other areas of the urinary lining such as the inside of the kidneys (renal pelvis) and the tubes connecting the kidneys to the bladder (ureters)

The Weill Cornell Medicine Genitourinary (GU) Oncology Program works with a wide range of GU specialists to tailor treatments for each patient depending on their disease type and if they have metastatic disease, which is when the cancer has left the bladder or other areas of the urinary system and spread to other parts of the body through the lymph nodes or bloodstream.

Here are some of the treatment options offered for bladder cancer patients.

Chemotherapy

Chemotherapy is a common treatment option for patients with bladder cancer and can be given at a number of times throughout the treatment process. Chemotherapy may be given directly into the bladder or into veins before surgery to make a tumor easier to remove, after surgery or radiation to kill remaining cancer cells, or as a main treatment option for patients with metastatic disease.

Radiation Therapy

Another type of treatment used for bladder cancer is radiation. Radiation may also be given throughout the treatment process. It can be used after surgery, as a main treatment for earlier-stage cancers that may not require or be able to receive surgery or chemotherapy, or as part of a treatment regimen for advanced or metastatic disease. Radiation is often given along with chemotherapy to help the radiation work better, which is known as chemoradiation.

Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses x-rays to kill tumor cells. This method is able to deliver radiation precisely to the tumors and may kill tumor cells with fewer doses over a shorter period compared to other types of radiation.

Immunotherapy

Immunotherapy drugs help the body’s immune system fight cancer by instructing the immune system to identify and destroy cancer cells.

There are a number of approved immunotherapy options that may be given to patients in a variety of different circumstances. Immunotherapy can be used in patients with non-muscle invasive bladder cancer though instillation in the bladder, into veins as an additional therapy after surgery, or into veins for advanced cancer.

One of the most common versions of immunotherapy are drugs called immune checkpoint inhibitors. Immune checkpoints are part of the natural body to keep the immune system from attacking normal cells (when this happens, we call it “autoimmunity”). Checkpoint inhibitors target “checkpoints”, or proteins on the immune cells, that cancer cells use to hide from the immune system. These drugs block the checkpoints allowing the body’s immune system to attack the cancer.

Surgery

Surgery is often done before or after other treatments in order to best maximize the results. A number of surgical techniques and options exist depending on the type of bladder cancer and whether or not it has spread beyond the urinary system. These range from endoscopic techniques where a tube is inserted into the urinary system to using cameras (often with the assistance of a robot) to open surgery with incisions through the skin. Sometimes the bladder needs to be removed and there are a number of techniques to either divert urine to the skin (often with a bag) or creation of a new bladder (called neobladder).

Clinical Trials

The Weill Cornell Medicine Genitourinary (GU) Oncology Program leads and participates in a number of clinical trials across a spectrum of disease areas, including bladder cancer. Our team is dedicated to evaluating new diagnostic and treatment approaches in order to develop the best options that benefit our patients. Clinical trials may be the right choice for some patients, and we encourage you to speak to your doctor about the options available to you.

Our team is currently leading a clinical trial evaluating the effects of adding radiation therapy to the immunotherapy drug atezolizumab, for the treatment of metastatic bladder cancer. The aim of this trial is to identify if the combination of radiation and immunotherapy may have the ability to boost the results of the immunotherapy drugs and may be more effective at killing tumor cells. Learn more about this trial here.

Another interesting trial has been developed based upon the laboratory work of one of our team members. For patients with bladder cancer invading the muscle layer and needing removal of the bladder (called cystectomy), the usual approach is chemotherapy followed by surgery. However, not all patients are able to safely receive the most effective chemotherapy drug called cisplatin. This trial is evaluating the use of an oral targeted drug called abemaciclib to take prior to surgery for these patients. Learn more about this trial here.

Antibody-drug conjugates are a type of targeted chemotherapy. To date, two have been approved by the U.S. Food and Drug Administration (FDA) in various situations. We currently have trials open to enrollment testing two of these antibody-drug conjugates, enfortumab and IMMU-132, either alone or in combination with other drugs.

Our team is continuously working on new research initiatives and clinical trial participation. You can find a full list of our open bladder cancer trials here.

What Patients with Prostate Cancer Should Know About PSMA Imaging and Therapy

Prostate cancer begins when cells in the prostate gland start to grow out of control. These cancerous cells may remain in the prostate or metastasize and spread to other parts of the body such as the bones, lymph nodes, liver, or lungs. 

Prostate-specific membrane antigen (PSMA) is a protein found on the surface of prostate cancer cells. PSMA-targeting can be used to locate, identify, or treat cancerous cells in both the prostate as well as cancerous cells that have metastasized in other organs. This targeting can involve attaching a radionuclide, a particle that gives off radiation, to different molecular agents, most often monoclonal antibodies or small molecule targeting agents (also known as peptides, ligands, or inhibitors). This combination attaches to the PSMA receptors located in the cancer cells. 

PSMA positron emission tomography (PET) scans are an imaging technique approved by the U.S. Food and Drug Administration (FDA). PSMA PET is able to precisely locate prostate cancer cells using a radioactive imaging agent that binds to prostate cancer cells to help localize them. This drug is injected into the body and attaches itself to PSMA proteins expressed by prostate cancer patients. The PET scan is then able to detect and pinpoint the prostate cancer tumors.

Weill Cornell Medicine was one of the first centers in the United States offering this technology for patients. PSMA PET is able to identify whether the cancer has spread beyond the prostate gland with higher accuracy than other imaging methods. 

The team at the Weill Cornell Medicine Genitourinary (GU) Oncology Program has been a pioneer for PSMA-targeted therapies for many years. PSMA-targeted radionuclide therapies lead the combination of radionuclide and molecular agents directly to the PSMA cell receptors. The ability for the targeting agents and the PSMA receptors to join together provides this therapy the ability to precisely target prostate cancer cells.  

In March 2022, the FDA approved 177Lu-PSMA-617 (also known as Lu 177 vipivotide tetraxetan or Pluvicto) for the treatment of patients with metastatic castration-resistant prostate cancer. Dr. Scott Tagawa, director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, was a member of the steering committee for the trial evaluating this treatment that led to the approval. 

“The first availability of tumor-targeted radionuclide therapy on a commercial basis will allow patients with more limited resources that might not have been able to travel for a clinical trial or overseas to receive the benefit of this treatment. The first successful phase 3 trial allows us in research to optimize the treatment, study it in earlier disease states, and explore combinations with other therapies with scientific merit. Even after this approval, I encourage clinical trial participation and/or referrals.”

Scott Tagawa, MD, MS

Weill Cornell Medicine will be one of the first centers able to offer this therapy to patients immediately for both our existing patients and those who may be referred to us if their local provider doesn’t immediately have access to this therapy.  

Our team continues to lead and participate in a number of clinical trials aimed at ongoing testing and research for additional PSMA-targeted imaging and treatment. We are one of few centers in the world currently able to provide treatment plans that involve both PSMA-PET imaging and multiple PSMA-targeted therapies for our patients, as well as the opportunity to participate in these types of clinical trials in order to further develop PSMA technology.  

The Weill Cornell Medicine Genitourinary (GU) Oncology Program provides top-notch care, knowledge, and expertise for our patients. We offer new patient appointments, second opinions, and ongoing care for people with genitourinary cancers, including prostate cancer. To learn more or to make an appointment with one of our physicians, please call us at 646-962-2072. If interested in a clinical trial, please email us at guonc@med.cornell.edu.

Studies Highlight Erdafitinib as an Encouraging Bladder Cancer Treatment Option

It has been an especially exciting time for our Genitourinary (GU) Oncology Program. Our team’s bladder (urothelial) cancer research recently made its way into two prestigious medical journals, with both studies highlighting erdafitinib – an oral inhibitor of fibroblast growth factor receptor (FGFR) – as an encouraging therapeutic option for the disease.

FGFR gene alterations are common in urothelial carcinoma and may be associated with low sensitivity to immunotherapy.

In a phase II study of 99 adults with locally advanced or metastatic urothelial carcinoma harboring FGFR gene alterations, Dr. Scott Tagawa and colleagues found erdafitinib to demonstrate impressive tumor control and tolerability. Forty percent of patients responded to the drug, and among the 22 patients who had previously received immunotherapy without success, the response rate jumped to 59 percent.

Weill Cornell Medicine“While not yet confirmed by randomized trial results, the fact that these patients with the unique molecular tumor selection were responsive to erdafitinib and resistant to prior lines of standard therapy makes this a pivotal study,” said Dr. Tagawa. “It’s wonderful to now have this option available for our patients early while awaiting results of the confirmatory randomized trial. It highlights the importance of genomic tumor testing.”

The research group’s findings were published in the New England Journal of Medicine and led to accelerated approval of erdafitinib as the first targeted drug for urothelial carcinoma from the United States Food and Drug Administration (FDA).

In addition to the use of next-generation sequencing of tumors to more precisely select those most likely to respond, the standard erdafitinib regimen also utilizes individualized dosing. Erdafitinib, partly depending on the dose used, is shown to induce increased phosphorus levels in the blood. As blood phosphorus levels are related to targeting of the key pathway (FGFR), the dose of erdafitinib is increased if phosphorus levels do not significantly increase in the absence of any significant side effect. In a retrospective analysis presented at the 2019 European Society of Medical Oncology (ESMO) annual meeting, erdafitinib-treated patients with increased blood phosphorus levels had improved outcomes.

Under the leadership of Dr. Bishoy Faltas, an in-depth analysis of the nuanced molecular characteristics of upper-tract urothelial carcinoma (UTUC) – an aggressive cancer occurring in the lining of the ureter and kidney – supports that erdafitinib has potential to improve the effectiveness of immunotherapy in this patient population.

Whole-exome and RNA sequencing of UTUC patient tumors yielded a number of insights into the biology of the disease – chiefly that it has low immune cells (T cells) and high expression of FGFR3. The research team found that inhibiting FGFR3 with erdafitinib increased the activity of BST2, a gene associated with immune system activation. Thus, combining FGFR3 inhibitors such as erdafitinib with a class of immunotherapy drugs called PD-1/PD-L1 inhibitors can serve as a viable treatment strategy for UTUC in the future.

Bishoy_Faltas_Headshot
“By inhibiting FGFR3, we are able to stimulate genes that are associated with activation of the anti-tumor immune response,” said Dr. Faltas. “In the future, we could potentially use this strategy to reverse the T-cell depletion in these tumors.”

Findings from Dr. Faltas et al. were published in Nature Communications.

Erdafitinib is under further investigation and development in an ongoing clinical trial at Weill Cornell Medicine and NewYork-Presbyterian.

A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Erdafitinib Plus JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Subjects with Metastatic or Surgically Unresectable Urothelial Cancer with Selected FGFR Gene

We are proud to draw upon our longstanding expertise in the bladder cancer field to lead advancements in the understanding and care of this disease, and we hope that sharing our findings will prompt additional discoveries.

 

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