Bladder Cancer – From the Basics to State-of-the-Art

One of the many ways Weill Cornell Medicine and NewYork-Presbyterian provide supportive resources to the community is by offering physician-led presentations and Q&A sessions in the Myra Mahon Patient Resource Center.

Two weeks ago, Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, presented to and educated people in the local community about bladder cancer. His presentation was titled, “Bladder Cancer: From the Basics to State-of-the-Art.” Following the presentation, all attendees were invited to ask Dr. Tagawa questions.

Key topics from Dr. Tagawa’s presentation included the most common risk factors for bladder cancer, different types of bladder cancer (also known as clinical phases), and corresponding treatment options, research, as well as the benefits of utilizing an individualized approach to treatment, also known as precision medicine.

Highlights from Dr. Tagawa’s presentation are outlined below.

Bladder Cancer Risk FactorsScreen Shot 2017-12-14 at 9.22.30 AM

Dr. Tagawa noted that anyone can be diagnosed with bladder cancer, however, factors such as age and exposure to cigarette smoke may increase the risk of bladder cancer from developing. Most people who are diagnosed with bladder cancer are older in age. In fact, the average age at diagnosis is 73. In addition, bladder cancer is twice as common among Caucasians as African Americans.

Clinical Phases of Bladder Cancer and Corresponding Treatment Options

BladderCancer_5Dr. Tagawa highlighted the importance of using a uniform method for developing and testing biomarkers in bladder cancer, a disease with a high incidence of recurrence and expensive clinical surveillance. He also pointed out that most bladder cancers are of a type called transitional cell, affecting the same kinds of cells (transitional cells) that are usually the cancerous cells responsible for renal pelvis, ureter as well as kidney cancers. Dr. Tagawa described the four main phases of bladder cancer.

Pre-Cancer Diagnosis

The first phase is to assess symptoms in high-risk individuals, which defines those who are likely to develop bladder cancer. The most common symptom of bladder cancer is blood in the urine and testing to include assessment for the possibility of cancer would be beneficial for a high-risk population. Risk factors include, those who are aged 65 years or older, have used tobacco and has family history of cancer.

Often, the first test in the assessment of a patient with the symptom of blood in urine (or reddish urine) is a urinalysis, which is a test to assess for the presence of blood versus other elements that may appear like blood in the urine.  Other tests may include the assessment of other urine or blood factors, including assessment for infection. One test that is more specific for bladder cancer is a urine cytology, which looks at the urine under a microscope to detect abnormal appearing cells. If these cells are seen, a cancer diagnosis may be made, as the bladder has “shed” these cells into the urine. However, this test does not detect all cases of bladder cancer. Physicians may also want to perform blood tests or scans including, CT scan, MRI and ultrasounds.

“Superficial” Non-Muscle Invasive Disease

Non-muscle invasive disease means the cancer is confined to the inner lining of the bladder with no evidence that it has spread to another part of the pelvis or other organs. It used to be referred to as “superficial” bladder cancer, but this term is confusing since this stage of cancer often does invade into the first lining of the bladder. This type of bladder cancer comprises about 70% of all cases of newly-diagnosed bladder cancer. These patients are typically managed with resection (surgical removal of the cancerous parts of the bladder using a scope/camera), sometimes followed by intravesical therapy (usually immunotherapy with bacillus calmette-guerin), a process where the physician inserts a liquid drug directly into the bladder through a catheter. The drug can affect the cells lining the bladder without having major effects in other parts of the body.

Muscle Invasive Disease

In patients with muscle invasive disease, the cancer has spread into the muscle wall of the bladder. Those with this type of bladder cancer, which comprise of approximately 40% of all bladder cancer patients, are preferentially treated with systemic neoadjuvant chemotherapy followed by surgery to remove the bladder. Dr. Tagawa explained the different types of surgery patients may undergo if they are diagnosed with muscle invasive disease. The first is transurethral bladder tumor resection (TURBT), in which the surgeon removes the tumor using a tool with a small wire loop. Another form of surgery is a radical cystectomy, the removal of the whole bladder and possibly nearby tissues and organs. In addition, lymph nodes in the pelvis area are removed for both men and women, also known as a pelvic lymph node dissection. A selected subgroup of patients may have similar outcomes with a combination of initial TURBT surgery followed by chemotherapy and radiation.

Metastatic Disease

Patients with metastatic bladder cancer, accounting for approximately 15% of bladder cancer patients, have cancer that has extended through the bladder wall and invaded the pelvic and/or abdominal wall. Dr. Tagawa noted that while the other clinical states are treatable, if someone is going to pass away from bladder cancer, they would most likely be at the metastatic disease state. Dr. Tagawa highlighted that chemotherapy with platinum-based regimens remains the mainstay of first-line treatment for metastatic disease. He explained that if physicians combine platinum-based chemotherapy (e.g. cisplatin) with other treatments, patients will most likely benefit from positive clinical outcomes, resulting in tumor shrinkage and longer overall survival rates.

Systemic immunotherapy (administered into veins as opposed to only instillation in the bladder) is another treatment approach and one in which bladder cancer patients tend to have positive responses. The type of immunotherapy drugs given to patients with bladder cancer are known as immune checkpoint inhibitors, as they “release the brakes” on the immune system and allow immune cells to attack tumors. The first Food and Drug Administration (FDA)- approved immunotherapy drugs is tecentriq, also known as atezolizumab, which is an immune checkpoint inhibitor that selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor’s surface.  There are now five such drugs approved for bladder cancer – more than for any other cancer type.

Treatment Approaches in the Pipeline

Dr. Tagawa noted that we’ve come a long way in recent years with the most available treatment options than ever before for bladder cancer patients. He emphasized, though, that there is still room for improvement with the development of more treatments and additional treatment combinations to increase survival rates for patients. One of the ways physicians are able to do this is by utilizing precision medicine, treating each patient as an individual based on his or her own genetic makeup. For bladder cancer patients, physicians look at the different genes and whether the genetic mutations are within the tumor, or germline, to determine the best treatment options. Some of the most promising drugs for bladder cancer work best in the presence of certain altered genes. Another way clinicians are able to continue utilizing precision medicine is through clinical trials, which pave the way toward further scientific advances that could potentially find a cure for bladder cancer, in addition to other cancers. Weill Cornell Medicine and NewYork-Presbyterian offer many bladder cancer-specific trials that you can search for here.

Overall, Dr. Tagawa reinforced the benefit of working with a multidisciplinary team, which should include at least a surgeon, radiation oncologist and medical oncologist. He concluded his talk by emphasizing how clinical research has progressed over the years and what it has taught us – “we have seen translational therapy lead to real clinically relevant improvement for patients.”

Watch Dr. Tagawa’s full presentation below.

Movember 2017 is Here!

For nearly 10 years, we have been proud to participate in a month-long campaign to raise awareness and funds for men’s health each November, also known as Movember.

The campaign dates back to 2003 when two friends in Australia tried to bring back the moustache trend by growing out moustaches (or “mo’s” as they are commonly called in Australia) during the month of November. The following year, after realizing that this facial hair served as a conversation-starter, they decided to channel that energy to raise money for prostate cancer research.

Awareness (and mustaches) have grown over the years, and in 2007, Movember officially launched a global campaign to change the face of men’s health – literally and figuratively through increased awareness and funds. Another way people can get involved is by “moving” and setting a walking, running, biking or swimming goal and working to achieve it every day throughout Movember. Today, over 5 million people from more than 20 countries have collectively raised over $700 million dollars. The Movember Foundation uses this money to fund research around the world to reduce the number of men dying from prostate and testicular cancer, as well as mental health issues. Movember is committed to funding research that will reduce the number of deaths from prostate and testicular cancer by 50% by 2030.

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From L to R: Dr. Scott Tagawa, last year’s Movember Captain, Dr. Daniel Margolis, this year’s Movember captain

We’ve been proud Movember partners for nearly 10 years now and have benefitted from many Movember research grants to further our cancer research, most recently being named one of six teams to receive a 2017 Challenge Award from the Prostate Cancer Foundation (PCF) and the Movember Foundation to investigate new, cutting-edge treatments for metastatic prostate cancer.

This 2017 Movember-PCF Challenge Grant has funded our latest research developing new treatments for treatment-resistant advanced prostate cancer. More details on the grant and research it supports can be found here.
In past years, Movember-funded grants have supported our research in the following areas:

  • Blood tests that assess the tumor’s circulating DNA to predict reasons for treatment resistance.
  • Circulating tumor cell (CTC) tests to predict which patients are more or less likely to respond to hormonal therapy or chemotherapy.
  • Assessing the genome of initial tumors in the prostate compared to advanced, treatment resistant tumors.
  • Evaluating inflammation in adipose (fat) tissue around the prostate, which is associated with tumor growth.

Throughout the month of November, staff and physicians at Weill Cornell Medicine and NewYork-Presbyterian will be growing mustaches, exercising and raising funds for the Movember Foundation in support of our shared mission to cure cancer.

Get Involved!

  • Join our team by visiting https://moteam.co/wild-weill-cornell-mos
  • Grow a moustache and commit to going razor-free. It’s a great conversation starter to encourage friends and family members to donate to Movember.
  • Spin for a cure! Kill two birds with one stone. Get your workout in and support the Wild Weill Cornell Mos. Attend our cycling events on November 16th and 18th, with proceeds benefiting our team’s Movember fundraising goal.
  • Shave the date and celebrate the end of Movember by attending a happy hour. Stay tuned for final details including date and location.

Last year, we raised $13,000. We want to top that this year by raising $20K or more. Help us get there and remember that every dollar counts in the quest to cure cancer!

 

 

First-Ever Clinical Trial Testing PSMA-Targeted Antibody and Radioactive Alpha Particles for Treatment of Advanced Prostate Cancer

Radiation is one of the most common treatments for prostate cancer. Using radiation, physicians are able to cure some men with cancer confined to the prostate, as well as improve symptoms for men with metastatic disease. There are many different types of radiation treatments.

One type of treatment includes injecting radioactive isotopes into the blood in order to directly reach the prostate cancer cells regardless of where they are located in the body, including the cells that have spread to the bone and other organs. For example, Radium-223 (Xofigo) is FDA-approved to treat prostate cancer that has metastasized to the bone and has been shown to improve both the quality and duration of the lives of men with advanced prostate cancer.

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Red marker = PSMA, Green = radiation, demonstrating that the drug targets the cancer cell directly.

Radioimmunotherapy or radioligand therapy involves the practice of attaching a radioactive isotope to a cancer-targeting antibody or small molecule that binds only to a specific cancer-related molecule on a tumor cell. This is similar to a “lock and key” scenario, where the antibody or molecule resembles the key that will only recognize a very specific lock (the cancer-related molecule).

Essentially all prostate cancers have a specific “lock” called prostate-specific membrane antigen (PSMA). This “lock” is a protein that sits on the surface of most prostate cancer cells but is absent from most other normal places in the body.

Physicians and scientists have engineered very specific “keys” in the form of monoclonal antibodies and molecules that will bind only to PSMA. When we attach radioactive particles to these keys, we are able to deliver what we call “molecularly targeted” radiotherapy.

For example, J591 is a monoclonal antibody (an engineered protein) that recognizes PSMA. Actinium-225 (225Ac) is a small radioactive particle that emits alpha-particles, a powerful form of radiation requiring fewer particles to cause damage to the cancer cells. When these are attached to one another, we call the compound 225Ac-J591 (a radioactive particle linked with a monoclonal antibody). It is designed so that J591 will recognize the PSMA on the prostate cancer cells and bring the radioactive particle 225Ac with it into prostate cancer cells wherever it goes in the body.

Our physicians and scientists are building on prior laboratory-based research presented at the 2017 Meeting for the Annual Association for Cancer Research (AACR) and are now studying the role this experimental therapy may have for men with advanced prostate cancer that has spread throughout the body. Thanks to generous support from the Prostate Cancer Foundation and the NIH SPORE award, Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, and his team are conducting the first-ever clinical trial testing the PSMA-targeted antibody and radioactive alpha particles (225Ac-J591) for treatment of advanced prostate cancer. This promising new and unique approach has the potential to lead to another treatment option for those patients who are not experiencing the best clinical outcomes possible from standard of care therapies. Some men in Germany have received 225Ac linked to PSMA-617 with a handful of cases published with impressive responses. However, no formal studies have been performed and there are reports of bothersome dry mouth (xerostomia) and the potential for delayed kidney damage (seen in mice).

“We look forward to advancing science and also making this treatment available to men with advanced prostate cancer in the near future, says Dr. Scott Tagawa. “Our goal is to translate the existing knowledge base into true clinical gains for prostate cancer patients and it’s great that in October, 2017, we are able to treat our first patient.”