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.

Prevalence and Clinical Outcomes of Advanced Prostate Cancer Patients with Inherited DNA-Repair Mutations

DNA Helix_NCICollaborative work has shown that approximately 12% of men with advanced prostate cancer have inherited, or germline, DNA-repair mutations that disrupt the normal function of the genes involved in repairing damaged DNA. Somatic alterations in DNA-repair pathways are also common in prostate cancer, particularly in late-stage disease. Somatic alterations affect only tumor cells, but are not inherited or passed on. Inherited mutations in DNA-repair genes – such as BRCA2, ATM, and CHEK2 – are associated with an increased risk of several other cancers as well as prostate cancer, including breast, ovarian, and pancreatic cancer. In particular, mutations in BRCA2, associated with 1.8% of overall prostate cancer cases, have been associated with more aggressive prostate cancer characteristics and worse outcomes, including increased risk of recurrence and poorer overall survival rates.

As a result of the increasing number of men with these types of mutations, the National Comprehensive Cancer Network (NCCN) guidelines have recently changed, now recommending genetic testing for all men with metastatic prostate cancer.

Weill Cornell Medicine

“Genetic testing for inherited mutations may provide some men with prognostic information about their prostate cancer risk,” says Dr. Scott Tagawa, Director of the Weill Cornell Medicine and NewYork-Presbyterian Genitourinary (GU) Oncology Program. “Even more importantly, genetic testing can also be used to inform screening of family members and may increasingly inform precision-medicine based approaches to manage the disease using specific molecular features such as DNA-repair genes,” says Dr. Tagawa.

How do Inherited Mutations Impact Treatment?

Clinical research studies are continually being conducted to investigate new ways to treat advanced prostate cancer patients with germline DNA-repair mutations since these patients comprise a unique subset of patients. Currently, little has been known about whether DNA-repair mutation status impacts benefit from standard therapies for the disease and this is just one area that needs to be researched in order to specifically tailor treatment options for this subset of patients.

Weill Cornell Medicine and NewYork-Presbyterian’s Drs. Himisha Beltran, Scott Tagawa and David Nanus, along with collaborators from around the globe, address this in research published today in the high impact factor journal European Urology and simultaneously presented at the American Society of Oncology (ASCO) 2018 Genitourinary (GU) Cancers Symposium by Dr. Misha Beltran. The researchers reviewed 390 medical records of patients who previously participated in a New England Journal of Medicine (NEJM) study examining men with advanced prostate cancer with known germline DNA-repair mutations and those without these mutations. The goal of the research was to determine whether germline mutations in DNA-repair genes impact the benefit of standard therapies for metastatic prostate cancer, such as docetaxel chemotherapy and androgen receptor signaling inhibitors abiraterone acetate and enzalutamide. Results showed that all patients appeared to benefit from standard therapies similarly to other metastatic prostate cancer patients, regardless of germline mutation status.

“The data suggest that metastatic prostate cancer patients with inherited mutations in DNA damage repair genes, including those with BRCA2 mutation, derive similar benefit from standard of care therapies in terms of both response rate and progression-free survival,” says Dr. Scott Tagawa. “While we continue to investigate additional agents thought to preferentially benefit those with DNA repair alterations, current evidence indicates that detection of any of these mutations should not prevent metastatic prostate cancer patients from receiving standard therapies including taxanes, abiraterone and enzalutamide, as standard of care treatment.”

Additionally, sophisticated genetic analysis and testing may be performed by genetic counselors and widely-available commercial testing is also available to physicians and patients. Dr. Panagiotis Vlachostergios, fellow and medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian, presented research at ASCO Genitourinary (GU) Cancers Symposium focused on using a commercial 30-gene panel to test men with localized prostate cancer and advanced prostate cancer for the presence of inherited gene mutations. Out of the 17 men with localized disease and 35 men with metastatic prostate cancer, eight of 52 (15%) were found to have a germline alteration. A higher percentage of men with an inherited mutation had localized (23.5%) versus advanced disease (11.4%), though testing might have been biased towards those with family history of cancer or those diagnosed with high-grade cancer at earlier age.

Both the results published in European Urology and research presented at the 2018 ASCO GU Cancer Symposium underscore the importance of genetic testing to determine what, if any, mutations may be present in prostate cancer in order to determine the best possible treatment options. While the published data supports the use of standard therapies in those with metastatic prostate cancer who have germline DNA-repair mutations, not all patients respond to these types of treatment, demonstrating the need for alternate treatment options for this patient population. Weill Cornell Medicine and NewYork-Presbyterian are in the process of opening several clinical trials to include men with prostate cancer in need of different lines of therapy. Clinical trials testing PARP inhibitors, a drug target for cancer therapy that appears to be more effective in prostate cancer patients with DNA-repair mutations, are ongoing and may offer additional therapy options for this group of patients in the near future.

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